Objective: To examine the associations of fibroblast growth factor 19 (FGF19), its co-receptor KLB gene and its receptor FGFR4 with susceptibility to sarcopenia, so as to provide insights into elucidation of sarcopenia pathogenesis and formulation of precision interventions for sarcopenia. Methods: A case-control study was conducted. Patients with sarcopenia at ages of 60 years and older included in the Zhejiang Provincial Elderly Health Surveillance Cohorts were selected as the sarcopenia group, and normal residents at ages of 60 years and older were served as controls. Subjects' demographics were collected using questionnaire surveys, and the height, body weight, appendicular skeletal muscle mass and grip strength were measured. Genomic DNA was extracted from blood samples for multiplex PCR targeted capture. The associations between the KLB gene single-nucleotide polymorphisms (SNPs) and susceptibility to sarcopenia were evaluated using multivariable logistic regression models. Results: There were 200 cases in the sarcopenia group, including 91 men and 109 women, and 180 cases in the control group, including 70 men and 110 women. All SNPs satisfied the Hardy-Weinberg equilibrium, and the minor allele frequencies were all > 0.05. There were no significant differences in the distribution of SNPs between the sarcopenia and control groups (all P>0.05). Multivariable logistic regression analysis showed that the SNP rs2687968 locus in the KLB gene was significantly associated with the susceptibility to sarcopenia among the elderly men (superdominant model), and individuals carrying the AC allele had a 2.332-fold higher risk of sarcopenia than those carrying the AA/CC allele (95%CI: 1.882-3.313). Conclusions KLB gene may correlate with the susceptibility to sarcopenia among the elderly men.

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To examine the effect of dietary behaviors on handgrip strength loss among the elderly, so as to provide insights into the prevention of handgrip strength loss. Methods : Based on the health surveillance cohort among the elderly in Zhejiang Province, two villages or communities were randomly sampled from each of Shaoxing and Zhoushan cities using a multi-stage cluster sampling method, and all residents that had lived in local areas for one year and longer and had an age of 60 years and older were enrolled. Participants' demographics, dietary behaviors, smoking, drinking, and exercise were collected through questionnaire surveys, and the height, body weight and handgrip strength were measured. The handgrip strength loss was diagnosed according the 2019 Consensus Update on Sarcopenia Diagnosis and Treatment proposed by Asian Working Group for Sarcopenia, and the effect of dietary behaviors on handgrip strength loss was examined using a multivariable logistic regression model. Results: A total of 1 265 residents were enrolled, with a mean age of (70.67±7.30) years, and including 565 men (44.66%) and 700 women (55.34%). The overall prevalence of handgrip strength loss was 42.85% among the participants, and the prevalence was 40.35% in men and 44.86% in women, respectively. Multivariable logistic regression analysis showed that nut intake for 1 to 3 times a week (OR=0.180, 95%CI: 0.088-0.367) and for 4 to 6 times a week (OR=0.241, 95%CI: 0.113-0.514) led to a reduced risk of handgrip strength loss among the elderly, and intake of sugary drinks for 4 to 6 times a week led to an increased risk of handgrip strength loss among the elderly (OR=2.298, 95%CI: 1.120-4.714) after adjustment for age, body mass index, educational level and exercise. Conclusion Intake of nuts and sugary drinks may affect the development of handgrip strength loss among the elderly.

ObjectiveTo take COVID-19 as an example to understand the sense of security and anxiety of students in Sichuan province under major public crisis events， and to provide references for psychological education and intervention under the situation of normalized COVID-19 prevention and control. MethodsIn June 2020， a total of 7 319 students from colleges， middle schools and primary schools in Sichuan province were surveyed via Wenjuanxing platform by Security-Insecurity Questionnaire （S-I） and Self-rating Anxiety Scale （SAS）. ResultsThe SAS score of students in Sichuan province was （41.52±9.90）， and the S-I score was （29.88±11.60）， the S-I score of male students was higher than that of female students， and the SAS score was lower than that of female students， the differences were statistically significant （t=5.961， -2.430， P<0.01）. There were significant differences in the total scores of S-I and SAS among students in different academic stages （F=122.579， 60.950， P<0.01）. The total score of S-I and the scores of each dimension were negatively correlated with SAS score （r=-0.553~-0.471， P<0.01）. Linear regression analysis showed that the regression model fitted well （adjusted R²=0.274）， and the model was statistically significant （F=40.802， P<0.01）. Emotional security （β=-0.441， P<0.01） was a significant negative predictor of anxiety. ConclusionUnder major public crisis events， students have a high level of anxiety and a low sense of security. Anxiety and security level are significantly different regarding different genders and school levels. Security has a negative predictive effect on anxiety.

Objective To investigate the risk assessment ,prevention and management for perioperative stroke in elderly patients with hip fractures. Methods A total of 179 patients aged 65 years and older were admitted to our department due to hip fracture. In managements of perioperative stroke ,the preoperative risk assessment and the management of stroke ,identifying the risk population for stroke prevention ,controlling risk factors of the preoperative stroke ,intraoperative monitoring , postoperative treatment ,etc.were studied retrospectively.The incidence of perioperative stroke was recorded and analyzed. Results Of 179 patients with hip fracture ,overviews of diagnosis and treatment were as follows.Twenty-four (24/179 ,13.41% ) cases did not receive operative treatments.Head and neck CT angiography(CTA)-showed severe stenosis or occlusion of intracranial artery and internal carotid artery were in 9(5.03% ,9/179)patients ,of whom the 5(2.79% ,5/179) cases underwent cerebrovascular digital subtraction angiography (DSA ) ,balloon dilation and stent implantation ,then received the operation for hip fracture 10 days later ,finally were discharged uneventfully.1 (0.56% ,1/179 ) patient underwent orthopaedic surgery due to the results of DSA showing no indication of interventional therapy ,and was discharged unevenfully.3 (1.68% ,3/179 ) patients refused to receive the further DSA examination or interventional therapy ,strongly demanded for orthopaedic surgery and would take the surgical risk ,and were discharged uneventfully.2(1.12% , 2/179)patients were found to have cerebral aneurysm diagnosed by CTA and DSA ,and underwent surgery for hipfracture without special treatment.2(1.12% ,2/179)patients were diagnosed as new occurrence of cerebral infarction before the operation ,and received head and carotid stenting at the department of cerebrovascular surgery ,followed by combined antithrombotic therapy of aspirin , clopidogrel and low molecular weight heparin for 4 weeks ,then underwent orthopaedic surgery for hip fracture.2 (1.12% ,2/179 ) patients were diagnosed as new cerebral infarction after orthopaedic surgery ,then were transferred to the department of neurology for treatment. Conclusions The thorough preoperative risk assessment and management of stroke ,reasonable perioperative antiplatelet and anticoagulation therapy ,intense intraoperative monitoring and active postoperative complications management make it possible for high-risk and new ischemic stroke patients with hip fractures to receive early orthopaedic treatment.

OBJECTIVETo identify and assess the potential public health risks of emergency events of infectious disease in the surrounding areas of Hangzhou during the 11th G20 summit, and to assess their impacts on the G20 summit.

METHODSThe surrounding cities of Hangzhou included Ningbo, Wenzhou, Jiaxing, Huzhou, Shaoxing, Jinhua, Quzhou, Zhoushan, Taizhou and Lishui. Background information on infectious diseases in Zhejiang province was collected, and the brainstorming and expert consultation methods were used to identify the risks. The local risks and the impact of local risks on the G20 summit were assessed.

RESULTSThe criteria for public health risk was first established. Through the assessments,a total of 27 kinds of infectious diseases in 4 types of public health risks were identified. The impact of these risks on Hangzhou G20 summit was divided into 1 item of high-risk, 12 items of medium risk and 14 items of low risk.According to the results of risk assessment, the recommendations for risk management of respiratory infectious diseases, intestinal infectious diseases, imported infectious diseases like Middle East respiratory syndrome and other infectious diseases were made. With risk management, Middle East respiratory syndrome was not occurred during the G20 summit, and the epidemic situation of other infectious diseases with middle or low risks was almost the same with that of past years.

CONCLUSIONSsThe public health risks of Hangzhou G20 summit from sudden infectious diseases in outlying areas are mainly medium and low risks. The recommendations on risk management provide a basis for reducing the adverse consequences of public health risks in the event of an outbreak of infectious diseases, avoiding the impact of various risk factors in the outlying areas on G20 summit.

Objective To investigate the sleep quality of older adults in Shaoxing City and to examine its influencing factors. Methods Based on a cross-sectional questionnaire survey, a cluster sampling method was adopted to collect participants. Five villages were chosen randomly from 20 in the Yuecheng district of Shaoxing. The respondents were adults aged more than 60 years in the 5 villages. In total,1 303 adults participated,including 603 men and 700 women,and the average age was(70.99±7.38). The information related to sociodemographic factors,health status,sleep characteristics,and behavioral and lifestyle factors were collected.A chi-square test and variance analysis were used to compare sleep quality and sleep duration among participants. An ordinal regression model was adopted to examine the factors influencing sleep quality. Results One hundred and ninety-six (15.0%) older adults reported that sleep quality was always bad during the past year, 180(13.8%)reported that sleep quality was bad occasionally, and 927(71.1%)reported that sleep quality was good every day.The average sleep duration of participants was(6.64±1.38)h per night,and sleep durations for older adults who reported that sleep quality was always bad, bad occasionally, and good every day were (4.21 ± 1.13) h, (6.12 ± 1.40) h, and (7.26 ± 1.39) h, respectively,and older adults with poor sleeping quality had a shorter sleep duration(F=421.828,P<0.001). Being a woman, more than 80 years old, not working, and taking sleeping pills were risk factors for poor sleep quality with ORs (95% CI) of 1.492 (1.132-1.964), 1.564 (1.108-2.206), 1.331 (1.015-1.747), and 14.614(7.164-29.844),respectively.Conclusions Elderly individuals in Shaoxing had poor sleep quality. The sleep quality of those who were women, were oldest and took sleeping pills is cause for concern. Encouraging them to engage in work may improve their sleeping status.

Studies on coat protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry) for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.
ADP-Ribosylation Factor 1 ; chemistry ; metabolism ; Animals ; Coatomer Protein ; chemistry ; metabolism ; Cytosol ; chemistry ; metabolism ; GTPase-Activating Proteins ; chemistry ; metabolism ; Humans ; Membranes, Artificial ; Rats

Objective To study the value of transcranial Doppler (TCD) combined with digital subtraction angiography (DSA) in the evaluation of intracranial vessels in patients with cerebral watershed infarction.Methods The clinical and imaging data of 97 patients with cerebral watershed infarction,admitted to our hospital from June 2008 to June 2011,were retrospectively analyzed.All patients underwent TCD and DSA examination.Comparative analysis of TCD and DSA for intracranial stenosis diagnosis and compensatory collateral circulation in these patients was performed,and the advantages and disadvantages of TCD and DSA in these cases were compared.Results Eight hundred and seventy-three intracranial vessels of the 97 patients were analyzed.TCD and DSA showed no significant differences in evaluation of vascular stenosis or occlusion (P=0.503).As to the collateral circulation,no significant differences between TCD and DSA were shown in the evaluation of anterior communicating artery compensatory (P=0.754),while TCD was more sensitive than DSA in the evaluation of ophthalmic artery compensatory (P=0.039),and DSA was more sensitive in evaluating the posterior communicating artery and pial artery compensatory (P=0.035 and P=0.000).The internal watershed infarction and cortical watershed infarction had significant differences in intracranial vascular stenosis or occlusion and collateral circulation (x2=9.762,P=0.002; x2=24.708,P=0.000).Conclusion Combining TCD and DSA can contribute to judge the intracranial vascular lesions and collateral circulation correctly.

Objective To evaluate the role of Fas/FasL signaling pathway in ulinastatin postconditioning-induced attenuation of apoptosis in the myocardial cells of patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty patients of both sexes,aged 21-59 yr,of ASA physical status Ⅱ or Ⅲ (NYHA class Ⅱ or Ⅲ),scheduled for elective cardiac valve replacement with CPB,were randomly divided into 2 groups (n =20 each):control group (group C),and ulinastatin postconditioning group (group U).In group U,ulinastatin 10 000 U/kg was perfused via the aortic root at 4 000-5 000 U·kg-1 ·min-1 starting from 5 min before aortic unclamping.In group C,the equal volume of normal saline was infused instead of ulinastatin.Myocardial specimens were taken from the right auricle at 45 min after aortic unclamping for determination of Fas,Fas ligand (FasL),caspase-8,Bcl-2 and Bax expression and cell apoptosis.The ratio of Bcl-2 expression to/Bax expression (Bcl-2/Bax) and apoptotic index were calculated.Results Fas,FasL,caspase-8 and Bax expression and apoptotic index were significantly lower,and Bcl-2 expression and Bcl-2/Bax were higher in group U than in group C.Conclusion Ulinastatin postconditioning attenuates apoptosis in the myocardial cells through inhibiting Fas/FasL signaling pathway in the patients undergoing cardiac valve replacement with CPB.