Sarcopenia is a clinical syndrome characterized by a decrease in skeletal muscle strength and quality， often accompanied by adverse outcomes such as falls， loss of function and weakness. The pathogenesis of sarcopenia is complex， and studies have shown that dysfunction due to impaired mitochondrial quality control is an important pathological factor in the occurrence and development. Traditional Chinese medicine（TCM） has been widely favoured for regulating mitochondrial homeostasis and preventing sarcopenia by virtue of its multi-target and multi-pathway advantages. They can play a role in the prevention and treatment of sarcopenia by regulating the mitochondrial quality control system to inhibit the occurrence of mitochondrial oxidative stress， regulate the balance of mitochondrial dynamics， inhibit mitochondrial autophagy， promote mitochondrial biosynthesis， resist the occurrence of mitochondrial apoptosis， and maintain the mitochondrial calcium and protein homeostasis. Based on this， the paper reviewed the relationship between mitochondrial quality control and sarcopenia， as well as the mechanism of TCM in intervening the mitochondrial quality control system to treat sarcopenia， in order to provide a new idea for the prevention and treatment of sarcopenia by TCM and to a theoretical basis for the clinical research on TCM intervention in sarcopenia.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

The paper reports a rarely case of hemophagocytic syndrome complicated with thrombotic microangiopathy, first presented with fever of unknown origin. A 37-year-old female patient mainly presented with fever, hemolytic anemia, thrombocytopenia, and progressive decline in renal function. After infusion of fresh frozen plasma and high dose of glucocorticoid after double plasma exchange, the patient showed good prognosis, no further fever or hemolysis occurred, recovered platelet and renal function. After acute episode phase, kidney biopsy was performed and acute tubular necrosis was diagnosed. During the follow-up period, the disease did not recur, and the renal function was normal.

Objective:To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

To evaluate the efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over 75 years. A total of 82 patients with AF who underwent LAAO successfully in Beijing Anzhen Hospital from March 2014 to March 2019 were divided into two groups according to age: the elderly group (aged>75 years) and the young group (aged ≤75 years). Risk of perioperative complications and incidence of ischemic stroke and major bleeding during follow-up were retrospectively analyzed. The results showed that there were no significant differences in procedure-related ischemic stroke(0 vs.1.6%, P=0.768) and major bleeding (0 vs.1.6%, P=0.768) during perioperative period between the two groups. No complications as death or pericardial tamponade occurred in the two group. During a (25.9±15.9) months period of followed up, ischemic stroke event rate was 3.6/100 person-years in the elderly group and 4.9/100 person-years in the young group, respectively. Major bleeding event rate was 2.5/100 person-years in the elderly group and 0/100 person-years in the young group, respectively. Compared with the expected ones, the relative risk reduction (RRR) of stroke in the elderly group was more profound than that in the young group (32.0% vs. 25.0%), while the risk of major bleeding in the young group was significantly lower than that in the elderly group (RRR 100% vs. 56.9%). Therefore, LAAO might be suitable for stroke prevention in the elderly AF patients.

OBJECTIVE：To establish the f ingerprint of Qinlian runfei decoction，determine the contents of 11 components， and conduct cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）. METHODS ：HPLC method was used. The determination was performed on ZORBAX Eclipse Plus C 18 column with mobile phase consisted of acetonitrile- 0.05％ phosphoric acid solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 260 nm， and column temperature was 30 ℃. The sample size was 10 μL. Using wogonoside as reference，HPLC fingerprints of 10 batches of Qinlian runfei decoction were drawn and the similarity evaluation was conducted with Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition），the common peaks were also confirmed ；the contents of 11 components in Qinlian runfei decoction were determined by the same method. SPSS 21.0 software was used for clus ter analysis ，and SIMCA 14.0 software was used for OPLS-DA to screen marker components affecting quality. RESULTS ：There were 21 common peaks in 10 batches of Qinlian runfei decoction ，and the similarity with control fingerprint was greater than 0.98. A total of 11 common peaks were identified ， which were rutin ， forsythiaside A ， forsythiaside B ， iris， irigenin， baicalin， forsythiaside， wogonoside， baicalein， irisflorentin and wogonin. The line ar ranges of 11 components were 9.960 0-49.800 0，1.974 0-9.870 0，0.672 0-3.360 0，0.960 0-4.800 0，0.549 0- 2.745 0，5.040 0-25.200 0，1.374 0-6.870 0，0.615 0-3.075 0，0.759 9-3.795 0，0.162 0-0.810 0，0.042 0-0.210 0 μg（all r＞ 0.999）； RSDs of precision ， stability （48 h） and repeatability tests were less than 2％ ； the average recoveries were 95.81％-100.29％ with RSDs of 0.43％-1.73％（n＝6）；the contents were 8.924 4-12.820 8，0.352 2-0.868 7，0.435 6-0.711 2， 0.389 8-1.309 0，0.335 8-0.530 1，1.680 5-4.542 3，0.701 8-1.584 2，2.240 2-5.442 5，2.351 0-5.558 9，0.106 0-0.182 2，0.076 8- 0.128 9 mg/g，respectively. The results of cluster analysis showed that when class spacing was 10，it could be divided into two groups，S1-S3 and S 4-S10；when the class spacing was 5，the second class could be divided into two categories ，S6，S7，S9 were clustered into one category ，and S 4，S5，S8，S10 were clustered into one category. The results of OPLS-DA analysis showed that S6，S7 and S 9 were at the top of the figure ，S4，S5，S8 and S 10 were at the lower left side of the figure ，and S 1-S3 were at the lower right side of the figure ，which was consistent with the cluster analysis results ；VIP values of baicalin ，iris，forsythiaside A ， baicalein and wogonoside were all greater than 1. CONCLUSIONS ：Established fingerprint and content determination methods have high precision and good stability. Combined with multivariate statistical analysis ，it can be used for the quality control of Qinlian runfei decoction. Five components as baicalin are the marker components affecting the quality of Qinlian runfei decoction.

Methods: Total 106 diabetic patients who had undergone PKP and had received anti-osteoporosis treatment for osteoporotic vertebral compression fracture were enrolled and allocated into the following two groups: group I (n=52, zoledronic acid) and group II (n=54, zoledronic acid plus teriparatide). The operating time, bone cement volume, and complications related to anti-osteoporosis treatment or PKP, if any, were recorded. The Visual Analog Scale (VAS) score and Oswestry Disability Index (ODI) were assessed at admission, at discharge, and at the final follow-up. Dual-energy X-ray absorptiometry scan of the hip for the measurement of the bone mineral density (BMD) was performed preoperatively and at the final follow-up for all the patients. Results: There was no significant difference in the age, body mass index, bone cement volume, or follow-up time of the groups. The mean follow-up duration was 22.5±1.6 months. All the patients had improved VAS and ODI, and group II had significantly better clinical outcomes than group I. All the patients had increased BMD at the latest follow-up, while group II exhibited significantly more improvement. The prevalence of NVF was lower in group II (11.5% vs. 7.4%, p=0.523). Male patients had a higher prevalence of NVF although the difference was not statistically significant. Conclusions Combination therapy with zoledronic acid and teriparatide could improve the clinical outcomes, and BMD and had the potential to reduce NVF in diabetic patients following PKP.

Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Objective To evaluate the role of non?invasive fractional flow reserve (FFR) derived from coronary CT angiography (CCTA) in assessing the hemodynamic relevance of myocardial bridging (MB). Methods A total of 60 patients without obstructive coronary artery disease but with CCTA?confirmed MB of the left anterior descending coronary artery and 30 patients with negative CCTA findings as control group were retrospectively included in this study. The 60 patients with MB were divided into 2 groups (superficial and deep MB group) according to the depth of MB. Age and sex were matched among three groups. The location, length, depth, and degree of systolic compression of the MB were measured. The FFRCT values (including systolic and diastolic phases) were measured at three points (segments 1 to 2 cm proximal to a MB, mid?tunneled segment and segments 1 to 2 cm distal to the MB) by cFFR software. Patients with FFRCT<0.75 were deemed to have hemodynamic relevance (abnormal group). χ2 test, ANOVA test, Mann?Whitney U test, Kruskal?Wallis H test and logistic regression model were used for statistical analysis. Results The FFRCT values decreased from diastolic phase to systolic phase in deep MB group [0.90 (0.81-0.94) vs. 0.93 (0.91-0.97), Z=-2.172, P=0.03]. Compared to control group, the FFRCT values decreased in both diastolic phase and systolic phase in superficial MB group as well as deep MB group [systole 0.92 (0.90-0.94) control vs. 0.84 (0.77-0.88) superficial vs. 0.67 (0.50-0.88) deep, H=37.193, P<0.001; diastole 0.93 (0.89-0.94) control vs. 0.85 (0.73-0.92) superficial vs. 0.81 (0.65-0.87) deep, H=26.508, P<0.001]. Abnormal FFRCT values (<0.75) were found in 28 (47.7%) MB patients (9 superficial vs. 19 deep). The length (OR=1.067, 95% CI: 1.016-1.122, P=0.010) and depth (OR=2.028, 95%CI: 1.129-3.644, P=0.018) of MB were associated with the abnormal FFRCT values.Conclusions The FFRCT values of coronary artery distal to MB were lower than that without MB. Abnormal FFRCT values are more prevalent in deep MB. MB length and depth demonstrate moderate predictive value for an abnormal FFRCT value.