In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rh...Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH （1-34） in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 μg （200 U） daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment （4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P 〈0.01）. There was only a small but significant increase of femoral neck BMD after 18 months （2.6%, P 〈0.01） in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH （1-34） group than those in the elcatonin group after 6, 12, and 18 months （serum bone-specific alkaline phosphatase （BSAP） 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P 〈0.01; urinary C-telopeptide/creatinine （CTX/Cr） 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P 〈0.01）. rhPTH （1-34） showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% （6/112） in elcatonin group and 3.2% （11/341）in rhPTH （1-34）group （P=0.303）. Both treatments were well tolerated. Hypercaluria （9.4%） and hypercalcemia （7.0%） in rhPTH （1-34） group were transient and caused no clinical symptoms. Pruritus （8.2% vs. 2.7%, P=0.044） and redness of injection si展开更多
Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patien...Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.展开更多
Objective： To investigate the effects ofursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. Methods： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow cyt...Objective： To investigate the effects ofursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. Methods： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory efibcts of ursolic acid on the phosphorylation of the epidermal growth factor receptor （EGFR）, extracellular signal-regulated kinase （ERK）, c-Jun N-terminal kinase （JNK）, and p38 mitogen-activated protein kinase （p38 MAPK）, and the activity of B cell leukemia-2 （Bcl-2）, B cell leukemia-xL （Bcl-xL）, caspase-3, and caspase-9. Results： Ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration （IC50） values for 24, 48, and 72 h treatment were 26, 20, and 18 pmol/L, respectively. The apoptotic rates of 10, 20, and 40 μmol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. Ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 μmol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells （P〈0.05）. Cell proliferation was most significantly inhibited when treated with 10 and 20 μmol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 μmol/L U0126 （P〈0.01）. Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9. Conclusion： Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.展开更多
Background:Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both r...Background:Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both related to pulmonary hypertension (PH) development. This study investigated the effects of OSA on PH in patients with COPD and the associated factors. Methods: Consecutive patients with stable COPD were recruited for an observational cross-sectional study from September 2016 to May 2018 at Peking University Third Hospital. In total, 106 patients with COPD were enrolled and performed home portable monitoring and echocardiography. OSA was defined by an apnea hypopnea index (AHI)>10 events/h. Based on OSA absence or presence, patients were divided into the COPD with OSA and COPD without OSA groups. Factors affecting pulmonary artery pressure (PAP) and PH were identified using univariate analysis and logistic regression models. Results: In the 106 patients with COPD, the mean age was 69.52 years, 91.5% were men, and the mean forced expiratory volume in 1 s (FEV!) percentage of predicted was 56.15%. Fifty-six (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD were diagnosed as PH. Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00-50.00] mmHg vs. 31.00 [24.00-34.00] mmHg, P = 0.036). COPD with percent of night-time spent with oxygen saturation below 90%(T90)> 10% group had higher PAP than COPD with T90 < 1 % group (36.00 [29.00-50.00)] mmHg vs. 29.00 [25.50-34.00] mmHg, F = 7.889, P = 0.007). Univariate analysis revealed age, FEVi% predicted, T90, and Charlson index had statistically significant effects on PH. Multiple regression analysis showed a significant and independent effect of both FEVj% predicted (odds ratio [OR]= 3.46;95% confidence interval [Cl]: 1.15-10.46;P = 0.028) and AHI (OR = 3.20;95% Cl: 1.09-19.35;P = 0.034) on PH. Conclusions: Patients with COPD with OSA are more susceptible to PH, which展开更多
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
文摘Background Recombinant human parathyroid hormone （1-34） （rhPTH （1-34）） is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH （1-34） in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH （1-34） with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH （1-34） 20 μg （200 U） daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine （L1-4） and femoral neck bone mineral density （BMD）, fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. Results rhPTH （1-34） increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment （4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P 〈0.01）. There was only a small but significant increase of femoral neck BMD after 18 months （2.6%, P 〈0.01） in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH （1-34） group than those in the elcatonin group after 6, 12, and 18 months （serum bone-specific alkaline phosphatase （BSAP） 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P 〈0.01; urinary C-telopeptide/creatinine （CTX/Cr） 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P 〈0.01）. rhPTH （1-34） showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% （6/112） in elcatonin group and 3.2% （11/341）in rhPTH （1-34）group （P=0.303）. Both treatments were well tolerated. Hypercaluria （9.4%） and hypercalcemia （7.0%） in rhPTH （1-34） group were transient and caused no clinical symptoms. Pruritus （8.2% vs. 2.7%, P=0.044） and redness of injection si
基金supported by Improving the Ability of Diagnosis and Treatment of Difficult Diseases (ZLYNXM202009)。
文摘Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.
基金supported by the Hi-Tech Research and Development Program (863) of China (No. 2006AA02Z341)the Science and Technology Research Program of Zhejiang Province, China (No. 2008C30037)
文摘Objective： To investigate the effects ofursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. Methods： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory efibcts of ursolic acid on the phosphorylation of the epidermal growth factor receptor （EGFR）, extracellular signal-regulated kinase （ERK）, c-Jun N-terminal kinase （JNK）, and p38 mitogen-activated protein kinase （p38 MAPK）, and the activity of B cell leukemia-2 （Bcl-2）, B cell leukemia-xL （Bcl-xL）, caspase-3, and caspase-9. Results： Ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration （IC50） values for 24, 48, and 72 h treatment were 26, 20, and 18 pmol/L, respectively. The apoptotic rates of 10, 20, and 40 μmol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. Ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 μmol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells （P〈0.05）. Cell proliferation was most significantly inhibited when treated with 10 and 20 μmol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 μmol/L U0126 （P〈0.01）. Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9. Conclusion： Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.
文摘Background:Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both related to pulmonary hypertension (PH) development. This study investigated the effects of OSA on PH in patients with COPD and the associated factors. Methods: Consecutive patients with stable COPD were recruited for an observational cross-sectional study from September 2016 to May 2018 at Peking University Third Hospital. In total, 106 patients with COPD were enrolled and performed home portable monitoring and echocardiography. OSA was defined by an apnea hypopnea index (AHI)>10 events/h. Based on OSA absence or presence, patients were divided into the COPD with OSA and COPD without OSA groups. Factors affecting pulmonary artery pressure (PAP) and PH were identified using univariate analysis and logistic regression models. Results: In the 106 patients with COPD, the mean age was 69.52 years, 91.5% were men, and the mean forced expiratory volume in 1 s (FEV!) percentage of predicted was 56.15%. Fifty-six (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD were diagnosed as PH. Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00-50.00] mmHg vs. 31.00 [24.00-34.00] mmHg, P = 0.036). COPD with percent of night-time spent with oxygen saturation below 90%(T90)> 10% group had higher PAP than COPD with T90 < 1 % group (36.00 [29.00-50.00)] mmHg vs. 29.00 [25.50-34.00] mmHg, F = 7.889, P = 0.007). Univariate analysis revealed age, FEVi% predicted, T90, and Charlson index had statistically significant effects on PH. Multiple regression analysis showed a significant and independent effect of both FEVj% predicted (odds ratio [OR]= 3.46;95% confidence interval [Cl]: 1.15-10.46;P = 0.028) and AHI (OR = 3.20;95% Cl: 1.09-19.35;P = 0.034) on PH. Conclusions: Patients with COPD with OSA are more susceptible to PH, which
