In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a n...In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.展开更多
China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and ...China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.展开更多
AIM: To evaluate the clinical efficacy of salvianolic acidB (SA-B) on liver fibrosis in chronic hepatitis B.METHODS: Sixty patients with definite diagnosis of liverfibrosis with hepatitis B were included in the trial....AIM: To evaluate the clinical efficacy of salvianolic acidB (SA-B) on liver fibrosis in chronic hepatitis B.METHODS: Sixty patients with definite diagnosis of liverfibrosis with hepatitis B were included in the trial.Interferon-γ (IFN-γ) was used as control drug. Thepatients took orally SA-B tablets or received muscularinjection of IFN-γ in the double blind randomized test,The complete course lasted 6 months. The histologicalchanges of liver biopsy specimen before and after thetreatment were the main evidence in evaluation, incombination with the results of contents of serum HA,LN, Ⅳ-C, P-Ⅲ-P, liver ultrasound imaging, andsymptoms and signs.RESULTS: Reverse rate of fibrotic stage was 36.67 % inSA-B group and 30.0 % in IFN-γgroup. Inflammatoryalleviating rate was 40.0 % in SA-B group and 36.67 %in IFN-γ group. The average content of HA and Ⅳ-Cwas significantly lower than that before treatment. Theabnormal rate also decreased remarkably. Overallanalysis of 4 serological fibrotic markers showedsignificant improvement in SA-B group as comparedwith the IFN-γgroup. Score of liver ultrasound imagingwas lower in SA-B group than in IFN-γgroup (HA 36.7 %vs80 %,Ⅳ-C 3.3 % vs23.2 %). Before the treatment,ALT AST activity and total bilirubin content of patientswho had regression of fibrosis after oral administrationof SA-B, were significantly lower than those of patientswho had aggravation of fibrosis after oraladministration of SA-B. IFN-γ showed certain sideeffects (fever and transient decrease of leukocytes,occurrence rates were 50 % and 3.23 %), but SA-Bshowed no side effects.CONCLUSION: SA-B could effectively reverse liverfibrosis in chronic hepatitis B. SA-B was better than IFN-γ in reduction of serum HA content, overall decrease of4 serum fibrotic markers, and decrease of ultrasoundimaging score. Liver fibrosis in chronic hepatitis B withslight liver injury was more suitable to SA-B in anti-fibrotic treatment. SA-B showed no obvious side effects.展开更多
AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice we...AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.展开更多
Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with N...Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with NP caused by RMPP who were admitted to our hospital from January 2008 to December 2015, and the clinical manifestations, laboratory data, imaging performances, hospital courses and outcomes were analyzed. Results Twenty-five patients with NP caused by RMPP were collected, with a median age of 5.1 (4.0–7.9) years. The mean duration of fever and hospital stay was 21.0 ± 8.9 and 19.9 ± 9.9 days, respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein, interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the pleural fluid cell count, LDH and protein were also increased. 80.0% of the patients had pleural effusion;and a high incidence of lobar atelectasis and pulmonary consolidation was found the patients. The mean duration from the onset of symptoms to the discovery of necrotic lesions was 21.0 ± 6.9 days. 80.0% of the patients were administrated corticosteroids, and bronchoalveolar lavage was extracted separately from all patients. Of the 20 patients who presented with pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest drainage. All patients received prolonged courses of antibiotics (32.2 ± 8.7 days). All patients were dischaged home and recovered without surgical intervention;and chest lesions were resolved or only minimal residual fibrotic changes were residual within 3.0 (2.0–6.0) months. Conclusions Necrotizing pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good outcomes can be achieved with appropriate management.展开更多
AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected...AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.展开更多
Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of eme...Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society(CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association(CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association(CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association(CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association(BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and headup tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.展开更多
Since December 2019,an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China.As of 8 pm,31 January 2020,more than 20 pediatric cases have been reported in China.Of these cases,t...Since December 2019,an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China.As of 8 pm,31 January 2020,more than 20 pediatric cases have been reported in China.Of these cases,ten patients were identified in Zhejiang Province,with an age of onset ranging from 112 days to 17 years.Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCo V (the 4th edition) and current status of clinical practice in Zhejiang Province,recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health,the National Children's Regional Medical Center,Children's Hospital,Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.展开更多
The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou Jing Telescope) is a special reflecting Schmidt telescope. LAMOST’s special design allows both a large aperture (effecti...The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou Jing Telescope) is a special reflecting Schmidt telescope. LAMOST’s special design allows both a large aperture (effective aperture of 3.6 m–4.9 m) and a wide field of view (FOV) (5°). It has an innovative active reflecting Schmidt configuration which continuously changes the mirror’s surface that adjusts during the observation process and combines thin deformable mirror active optics with segmented active optics. Its primary mirror (6.67m×6.05 m) and active Schmidt mirror (5.74m×4.40 m) are both segmented, and composed of 37 and 24 hexagonal sub-mirrors respectively. By using a parallel controllable fiber positioning technique, the focal surface of 1.75 m in diameter can accommodate 4000 optical fibers. Also, LAMOST has 16 spectrographs with 32 CCD cameras. LAMOST will be the telescope with the highest rate of spectral acquisition. As a national large scientific project, the LAMOST project was formally proposed in 1996, and approved by the Chinese government in 1997. The construction started in 2001, was completed in 2008 and passed the official acceptance in June 2009. The LAMOST pilot survey was started in October 2011 and the spectroscopic survey will launch in September 2012. Up to now, LAMOST has released more than 480 000 spectra of objects. LAMOST will make an important contribution to the study of the large-scale structure of the Universe, structure and evolution of the Galaxy, and cross-identification of multiwaveband properties in celestial objects.展开更多
AIM:To evaluate the role and limitation of fast multiplanarspoiled gradient-recalled (FMPSPGR) MR dynamiccontrast scanning in the follow-up of patients with HCCtreated by transarterial chemoembolization (TACE).METHODS...AIM:To evaluate the role and limitation of fast multiplanarspoiled gradient-recalled (FMPSPGR) MR dynamiccontrast scanning in the follow-up of patients with HCCtreated by transarterial chemoembolization (TACE).METHODS:Twenty-two patients with 24 HCC lesionsconfirmed by biopsy or surgical resection underwentMR imaging in 4-9wks after TACE with a superconducting1.5 T MR scanner, including SE T1WI, T2WI and FMPSPGRdynamic contrast scanning. The signal intensities of alllesions on SE T1WI, T2WI and the enhancement patternson FMPSPGR dynamic contrast scanning were observed,and the comparison was made between MRI findingsand pathological results in ail the cases.RESULTS:Of the 24 lesions, the signal intensities werevarious on SE T1WI and T2WI. On T1WI, 13 lesionsappeared as hyperintense, 4 lesions were isointenseand the other 7 lesions were hypointensese.Histologically, hyperintense lesions showed on T1WIwere viable tumor or hemorrhage; isointensities werecoagulative necrosis or inflammatory infiltration;hypointensities were tumor, liquified necrosis,coagulative necrosis or inflammatory infiltration. OnT2WI, 15 lesions appeared as hyperintense, 3 lesionswere isointense and the other 6 lesions werehypointensese. Hyperintense lesions showed on T2WIwere residuals of viable tumor, hemorrhage, liquefiednecrosis or inflammatory infiltration; isointense lesionswere residuals of viable tumor or inflammatoryinfiltration; hypointense lesions were coagulativenecrosis. On FMPSPGR dynamic contrast scanning, 18of the 24 lesions enhanced on early-phase dynamicscanning conesponding to residuals of viable tumor andthe other 6 lesions had no enhancement at this phasebecause complete necrosis were seen in the histologicexamination. On delayed-phase dynamic scanning, 6lesions had permanent enhancement appeared asinhomogeneous hyperintensity and both residuals ofviable tumor and inflammatory infiltration were foundby histologic examination. 18 lesions were hypointenseat this phase and 8 of them coexisted with peripheralring-like enhancemen展开更多
The new century has witnessed a strategic breakthrough in unconventional oil ＆ gas.Hydrocarbon accumulated in micro-/nano-scale pore throat shale systems has become an important domain that could replace current oil ...The new century has witnessed a strategic breakthrough in unconventional oil ＆ gas.Hydrocarbon accumulated in micro-/nano-scale pore throat shale systems has become an important domain that could replace current oil ＆ gas resources.Unconventional oil ＆ gas plays an increasingly important role in our energy demand.Tight gas,CBM,heavy oil and asphaltic sand have served as a key domain of exploration ＆ development,with tight oil becoming a ＇bright spot＇ domain and shale gas becoming a ＇hotspot＇ domain.China has made great breakthroughs in unconventional oil ＆ gas resources,such as tight gas,shale gas,tight oil and CBM,and great progress in oil shale,gas hydrate,heavy oil and oil sand.China has an estimated（223-263）×10~8t of unconventional oil resources and（890-1260）×l0^（12）m^3 of gas resources.China has made a breakthrough for progress in unconventional oil ＆ gas study.New progress achieved in fine-grained sedimentary studies related to continental open lacustrine basin large-scale shallow-water delta sand bodies,lacustrine basin central sandy clastic flow sediments and marine-continental fine-grained sediments provide a theoretical basis for the formation and distribution of basin central reservoir bodies.Great breakthroughs have been made in unconventional reservoir geology in respect of research methodology ＆ technology,multi-scale data merging and physical simulation of formation conditions.Overall characterization of unconventional reservoirs via multi-method and multi-scale becomes increasingly popular and facilitates the rapid development of unconventional oil ＆ gas geological theory,method and technology.The formation of innovative,continuous hydrocarbon accumulation theory,the establishment of the framework of the unconventional oil ＆ gas geological theory system,and the determination of the implications,geological feature,formation mechanism,distribution rule and core technology of unconventional oil＆ gas geological study lays a theoretical foundation for extensive展开更多
In order to understand land use/land cover changes （LUCC） and the eco-environment response to LUCC in farming- pastoral zone of the northern China during the recent twenty years, Baotou prefecture was selected as a ...In order to understand land use/land cover changes （LUCC） and the eco-environment response to LUCC in farming- pastoral zone of the northern China during the recent twenty years, Baotou prefecture was selected as a case study area for investigation and quantitative evaluation. Technologies of remote sensing （RS）, global positioning system （GPS）, geographic information system （GIS）, and other statistical methods were employed to implement. Results showed that： （1） During the recent twenty years, the areas of forest lands, grasslands and water were reduced, whereas the areas of other types were enlarged. Parts of forest lands, grasslands, and waters had become farmlands, and about 31.5% of the changed grasslands transferred into unused lands. The newly increased farmlands mainly came from grasslands and unused lands. And the newly increased construction lands mainly came from grasslands and farmlands. （2） Regional eco- environmental quality decreased by 12.6%, for which the land degradation （especially the meadow degeneration） and the developing of the cultivated land were mainly responsible, and their contributions to the regional eco-environment changes were 51.84 and 23.63% respectively. （3） The tendency of LUCC and the eco-environment response to LUCC displayed spatial heterogeneity. It can be concluded that the present agricultural production mode was not sustainable in farming-pastoral zone of northern China. Land degradation, especially meadow degradation induced by over-trampling and overgrazing, and developing of cultivated land were mainly responsible for regional eco-environment deterioration. Changing the cultivated land to forest or grass, however, can relieve deterioration of local eco-environment to some extents. And in the farming-pastoral zone in the northern China, evaluating regional eco-environment responses to LUCC was very necessary due to its fragile eco-environments.展开更多
AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, la...AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, laparoscopic right colectomy develops relatively slowly. This study was designed to compare the outcomes of laparoscopic right hemicolectomy (LRH) with open right hemicolectomy (ORH) in the treatment of colon carcinoma. METHODS: Between September 2000 and February 2003, 30 patients with colon cancer who underwent LRH were compared with 34 controls treated by ORH in the same period. All patients were evaluated with respect to surgery related complications, postoperative recovery, recurrence and metastasis rate, cost-effectiveness and survival. RESULTS: Among 30 LRH, 2 (6.7%) were converted to open procedure. No significant differences were observed in terms of mean operation time, blood loss, post-operative complications, and hospital cost between LRH and ORH groups. Mean time for bowel movement, hospital stay, and time to resum?early activity in the LRH group were significantly shorter than those in the ORH group (2.24±0.56 vs 3.25±1.29 d, 13.94?.5 vs 18.25±5.96 d, 3.94±1.64 vs 5.45±1.82 d respectively, P<0.05). As to the lymph node yield, the specimen length and total cost for operation and drugs, there was no significant difference between the two groups. Local recurrence rate and metachronous metastasis rate had no marked difference between the two groups. Cumulative survival probability at 40 mo in LRH group (76.50%) was not obviously different compared to the ORH group (74.04%). CONCLUSION: LRH in patients with colon cancer has statistically and clinically significant advantages over ORH. Thus, LRH can be regarded as a safe and effective procedure.展开更多
The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing ...The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing in China and will remain an upward trend in the next 10 years. CVDs are the leading cause of death for Chinese in both urban area and rural area. Nowadays, 41.09% of deaths in rural area and 42.52% of deaths in urban area are caused by CVDs in China. The burden of CVDs remains heavy and has become an important public health problem. Effective strategies should be enforced urgently for the prevention of CVDs under the supervision of the government. In 2012, the Ministry of Health of China and 14 governmental departments jointly issued the Work Plan for Chronic Disease Prevention and Control in China （2012-2015）, a guideline for the prevention of chronic diseases, especially CVDs in China.展开更多
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the ...Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
基金supported(in part)by the Entrusted Project of National Center for Medical Service Administration,National Health and Family Planning Commission China(No.[2019]099)the First Level Funding of the Second Medical Leading Talent Project in Hubei Provincethe Special Project for Emergency of the Ministry of Science and Technology(2020YFC0841300)。
文摘In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
文摘China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.
基金the National 9~(th)Five-Year Breakthrough Scientific Project,No.96-906-08-02
文摘AIM: To evaluate the clinical efficacy of salvianolic acidB (SA-B) on liver fibrosis in chronic hepatitis B.METHODS: Sixty patients with definite diagnosis of liverfibrosis with hepatitis B were included in the trial.Interferon-γ (IFN-γ) was used as control drug. Thepatients took orally SA-B tablets or received muscularinjection of IFN-γ in the double blind randomized test,The complete course lasted 6 months. The histologicalchanges of liver biopsy specimen before and after thetreatment were the main evidence in evaluation, incombination with the results of contents of serum HA,LN, Ⅳ-C, P-Ⅲ-P, liver ultrasound imaging, andsymptoms and signs.RESULTS: Reverse rate of fibrotic stage was 36.67 % inSA-B group and 30.0 % in IFN-γgroup. Inflammatoryalleviating rate was 40.0 % in SA-B group and 36.67 %in IFN-γ group. The average content of HA and Ⅳ-Cwas significantly lower than that before treatment. Theabnormal rate also decreased remarkably. Overallanalysis of 4 serological fibrotic markers showedsignificant improvement in SA-B group as comparedwith the IFN-γgroup. Score of liver ultrasound imagingwas lower in SA-B group than in IFN-γgroup (HA 36.7 %vs80 %,Ⅳ-C 3.3 % vs23.2 %). Before the treatment,ALT AST activity and total bilirubin content of patientswho had regression of fibrosis after oral administrationof SA-B, were significantly lower than those of patientswho had aggravation of fibrosis after oraladministration of SA-B. IFN-γ showed certain sideeffects (fever and transient decrease of leukocytes,occurrence rates were 50 % and 3.23 %), but SA-Bshowed no side effects.CONCLUSION: SA-B could effectively reverse liverfibrosis in chronic hepatitis B. SA-B was better than IFN-γ in reduction of serum HA content, overall decrease of4 serum fibrotic markers, and decrease of ultrasoundimaging score. Liver fibrosis in chronic hepatitis B withslight liver injury was more suitable to SA-B in anti-fibrotic treatment. SA-B showed no obvious side effects.
基金the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491,No.81470840 and No.31400001100 Talents Program,No.XBR2011007h
文摘AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
基金This work was partially supported by Grants from Zheji-ang Province Natural Science Foundation of China(LY17H100004,LY18H100002)Social Development Program of Science Technology Department of Zhejiang Province(2015C33127)the Key Projects of Zhejiang Medicine and Health Research Fund(no.2018268955).
文摘Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with NP caused by RMPP who were admitted to our hospital from January 2008 to December 2015, and the clinical manifestations, laboratory data, imaging performances, hospital courses and outcomes were analyzed. Results Twenty-five patients with NP caused by RMPP were collected, with a median age of 5.1 (4.0–7.9) years. The mean duration of fever and hospital stay was 21.0 ± 8.9 and 19.9 ± 9.9 days, respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein, interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the pleural fluid cell count, LDH and protein were also increased. 80.0% of the patients had pleural effusion;and a high incidence of lobar atelectasis and pulmonary consolidation was found the patients. The mean duration from the onset of symptoms to the discovery of necrotic lesions was 21.0 ± 6.9 days. 80.0% of the patients were administrated corticosteroids, and bronchoalveolar lavage was extracted separately from all patients. Of the 20 patients who presented with pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest drainage. All patients received prolonged courses of antibiotics (32.2 ± 8.7 days). All patients were dischaged home and recovered without surgical intervention;and chest lesions were resolved or only minimal residual fibrotic changes were residual within 3.0 (2.0–6.0) months. Conclusions Necrotizing pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good outcomes can be achieved with appropriate management.
文摘AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.
文摘Syncope belongs to the transient loss of consciousness(TLOC), characterized by a rapid onset, short duration, and spontaneous complete recovery. It is common in children and adolescents, accounting for 1% to 2% of emergency department visits.Recurrent syncope can seriously affect children's physical and mental health, learning ability and quality of life and sometimes cardiac syncope even poses a risk of sudden death. The present guideline for the diagnosis and treatment of syncope in children and adolescents was developed for guiding a better clinical management of pediatric syncope. Based on the globally recent development and the evidence-based data in China, 2018 Chinese Pediatric Cardiology Society(CPCS) guideline for diagnosis and treatment of syncope in children and adolescents was jointly prepared by the Pediatric Cardiology Society, Chinese Pediatric Society, Chinese Medical Association(CMA)/Committee on Pediatric Syncope, Pediatricians Branch, Chinese Medical Doctor Association(CMDA)/Committee on Pediatric Cardiology, Chinese College of Cardiovascular Physicians, Chinese Medical Doctor Association(CMDA)/Pediatric Cardiology Society, Beijing Pediatric Society, Beijing Medical Association(BMA). The present guideline includes the underlying diseases of syncope in children and adolescents, the diagnostic procedures, methodology and clinical significance of standing test and headup tilt test, the clinical diagnosis vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic hypertension, and the treatment of syncope as well as follow-up.
文摘Since December 2019,an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China.As of 8 pm,31 January 2020,more than 20 pediatric cases have been reported in China.Of these cases,ten patients were identified in Zhejiang Province,with an age of onset ranging from 112 days to 17 years.Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCo V (the 4th edition) and current status of clinical practice in Zhejiang Province,recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health,the National Children's Regional Medical Center,Children's Hospital,Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
文摘The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou Jing Telescope) is a special reflecting Schmidt telescope. LAMOST’s special design allows both a large aperture (effective aperture of 3.6 m–4.9 m) and a wide field of view (FOV) (5°). It has an innovative active reflecting Schmidt configuration which continuously changes the mirror’s surface that adjusts during the observation process and combines thin deformable mirror active optics with segmented active optics. Its primary mirror (6.67m×6.05 m) and active Schmidt mirror (5.74m×4.40 m) are both segmented, and composed of 37 and 24 hexagonal sub-mirrors respectively. By using a parallel controllable fiber positioning technique, the focal surface of 1.75 m in diameter can accommodate 4000 optical fibers. Also, LAMOST has 16 spectrographs with 32 CCD cameras. LAMOST will be the telescope with the highest rate of spectral acquisition. As a national large scientific project, the LAMOST project was formally proposed in 1996, and approved by the Chinese government in 1997. The construction started in 2001, was completed in 2008 and passed the official acceptance in June 2009. The LAMOST pilot survey was started in October 2011 and the spectroscopic survey will launch in September 2012. Up to now, LAMOST has released more than 480 000 spectra of objects. LAMOST will make an important contribution to the study of the large-scale structure of the Universe, structure and evolution of the Galaxy, and cross-identification of multiwaveband properties in celestial objects.
基金Clinical Important Item of Chinese Health Ministry,No.97030220
文摘AIM:To evaluate the role and limitation of fast multiplanarspoiled gradient-recalled (FMPSPGR) MR dynamiccontrast scanning in the follow-up of patients with HCCtreated by transarterial chemoembolization (TACE).METHODS:Twenty-two patients with 24 HCC lesionsconfirmed by biopsy or surgical resection underwentMR imaging in 4-9wks after TACE with a superconducting1.5 T MR scanner, including SE T1WI, T2WI and FMPSPGRdynamic contrast scanning. The signal intensities of alllesions on SE T1WI, T2WI and the enhancement patternson FMPSPGR dynamic contrast scanning were observed,and the comparison was made between MRI findingsand pathological results in ail the cases.RESULTS:Of the 24 lesions, the signal intensities werevarious on SE T1WI and T2WI. On T1WI, 13 lesionsappeared as hyperintense, 4 lesions were isointenseand the other 7 lesions were hypointensese.Histologically, hyperintense lesions showed on T1WIwere viable tumor or hemorrhage; isointensities werecoagulative necrosis or inflammatory infiltration;hypointensities were tumor, liquified necrosis,coagulative necrosis or inflammatory infiltration. OnT2WI, 15 lesions appeared as hyperintense, 3 lesionswere isointense and the other 6 lesions werehypointensese. Hyperintense lesions showed on T2WIwere residuals of viable tumor, hemorrhage, liquefiednecrosis or inflammatory infiltration; isointense lesionswere residuals of viable tumor or inflammatoryinfiltration; hypointense lesions were coagulativenecrosis. On FMPSPGR dynamic contrast scanning, 18of the 24 lesions enhanced on early-phase dynamicscanning conesponding to residuals of viable tumor andthe other 6 lesions had no enhancement at this phasebecause complete necrosis were seen in the histologicexamination. On delayed-phase dynamic scanning, 6lesions had permanent enhancement appeared asinhomogeneous hyperintensity and both residuals ofviable tumor and inflammatory infiltration were foundby histologic examination. 18 lesions were hypointenseat this phase and 8 of them coexisted with peripheralring-like enhancemen
基金Funded by the National Key Basic Research and Development Program(973 Program),China(Grant 2014CB239000)China National Science and Technology Major Project(Grant 2011ZX05001)
文摘The new century has witnessed a strategic breakthrough in unconventional oil ＆ gas.Hydrocarbon accumulated in micro-/nano-scale pore throat shale systems has become an important domain that could replace current oil ＆ gas resources.Unconventional oil ＆ gas plays an increasingly important role in our energy demand.Tight gas,CBM,heavy oil and asphaltic sand have served as a key domain of exploration ＆ development,with tight oil becoming a ＇bright spot＇ domain and shale gas becoming a ＇hotspot＇ domain.China has made great breakthroughs in unconventional oil ＆ gas resources,such as tight gas,shale gas,tight oil and CBM,and great progress in oil shale,gas hydrate,heavy oil and oil sand.China has an estimated（223-263）×10~8t of unconventional oil resources and（890-1260）×l0^（12）m^3 of gas resources.China has made a breakthrough for progress in unconventional oil ＆ gas study.New progress achieved in fine-grained sedimentary studies related to continental open lacustrine basin large-scale shallow-water delta sand bodies,lacustrine basin central sandy clastic flow sediments and marine-continental fine-grained sediments provide a theoretical basis for the formation and distribution of basin central reservoir bodies.Great breakthroughs have been made in unconventional reservoir geology in respect of research methodology ＆ technology,multi-scale data merging and physical simulation of formation conditions.Overall characterization of unconventional reservoirs via multi-method and multi-scale becomes increasingly popular and facilitates the rapid development of unconventional oil ＆ gas geological theory,method and technology.The formation of innovative,continuous hydrocarbon accumulation theory,the establishment of the framework of the unconventional oil ＆ gas geological theory system,and the determination of the implications,geological feature,formation mechanism,distribution rule and core technology of unconventional oil＆ gas geological study lays a theoretical foundation for extensive
基金supported by the National Natural Science Foundation of China (40771019)
文摘In order to understand land use/land cover changes （LUCC） and the eco-environment response to LUCC in farming- pastoral zone of the northern China during the recent twenty years, Baotou prefecture was selected as a case study area for investigation and quantitative evaluation. Technologies of remote sensing （RS）, global positioning system （GPS）, geographic information system （GIS）, and other statistical methods were employed to implement. Results showed that： （1） During the recent twenty years, the areas of forest lands, grasslands and water were reduced, whereas the areas of other types were enlarged. Parts of forest lands, grasslands, and waters had become farmlands, and about 31.5% of the changed grasslands transferred into unused lands. The newly increased farmlands mainly came from grasslands and unused lands. And the newly increased construction lands mainly came from grasslands and farmlands. （2） Regional eco- environmental quality decreased by 12.6%, for which the land degradation （especially the meadow degeneration） and the developing of the cultivated land were mainly responsible, and their contributions to the regional eco-environment changes were 51.84 and 23.63% respectively. （3） The tendency of LUCC and the eco-environment response to LUCC displayed spatial heterogeneity. It can be concluded that the present agricultural production mode was not sustainable in farming-pastoral zone of northern China. Land degradation, especially meadow degradation induced by over-trampling and overgrazing, and developing of cultivated land were mainly responsible for regional eco-environment deterioration. Changing the cultivated land to forest or grass, however, can relieve deterioration of local eco-environment to some extents. And in the farming-pastoral zone in the northern China, evaluating regional eco-environment responses to LUCC was very necessary due to its fragile eco-environments.
基金Supported by Science and Technology Development Foundation of Shanghai,No. 024119106
文摘AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, laparoscopic right colectomy develops relatively slowly. This study was designed to compare the outcomes of laparoscopic right hemicolectomy (LRH) with open right hemicolectomy (ORH) in the treatment of colon carcinoma. METHODS: Between September 2000 and February 2003, 30 patients with colon cancer who underwent LRH were compared with 34 controls treated by ORH in the same period. All patients were evaluated with respect to surgery related complications, postoperative recovery, recurrence and metastasis rate, cost-effectiveness and survival. RESULTS: Among 30 LRH, 2 (6.7%) were converted to open procedure. No significant differences were observed in terms of mean operation time, blood loss, post-operative complications, and hospital cost between LRH and ORH groups. Mean time for bowel movement, hospital stay, and time to resum?early activity in the LRH group were significantly shorter than those in the ORH group (2.24±0.56 vs 3.25±1.29 d, 13.94?.5 vs 18.25±5.96 d, 3.94±1.64 vs 5.45±1.82 d respectively, P<0.05). As to the lymph node yield, the specimen length and total cost for operation and drugs, there was no significant difference between the two groups. Local recurrence rate and metachronous metastasis rate had no marked difference between the two groups. Cumulative survival probability at 40 mo in LRH group (76.50%) was not obviously different compared to the ORH group (74.04%). CONCLUSION: LRH in patients with colon cancer has statistically and clinically significant advantages over ORH. Thus, LRH can be regarded as a safe and effective procedure.
文摘The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing in China and will remain an upward trend in the next 10 years. CVDs are the leading cause of death for Chinese in both urban area and rural area. Nowadays, 41.09% of deaths in rural area and 42.52% of deaths in urban area are caused by CVDs in China. The burden of CVDs remains heavy and has become an important public health problem. Effective strategies should be enforced urgently for the prevention of CVDs under the supervision of the government. In 2012, the Ministry of Health of China and 14 governmental departments jointly issued the Work Plan for Chronic Disease Prevention and Control in China （2012-2015）, a guideline for the prevention of chronic diseases, especially CVDs in China.
基金Project supported by the National Basic Research Program(973)of China(No.2012CB518900)the National Natural Science Foundation of China(Nos.31160240 and 31260621)+2 种基金the National Major Scientific and Technological Special Project during the Twelfth Five-year Plan Period of China(No.2012ZX10002006)the Hangzhou Normal University Supporting Project(No.PE13002004042)the Natural Science Foundation of Jiangxi Province(No.20114BAB204016),China
文摘Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
