Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of 3326 residents aged ≥60 years with complete data were selected as the survey participants. Multiple logistic regression models and restricted cubic splines (RCS) were used to assess the association between PA duration/volume and sarcopenia. Results In 10 provinces (autonomous regions) of China, the prevalence of sarcopenia in the elderly aged 60 years and above was 5.5% (95%CI: 4.7%, 6.2%). The logistic regression analysis showed that compared with the elderly reporting 0-7.0 h·week⁻¹ in LPA duration, the risk of sarcopenia in the elderly with LPA duration of >14.0-21.0 h·week⁻¹ was reduced by 51% (OR=0.49, 95%CI: 0.26, 0.96). Compared with the elderly with total physical activity ≥15.0 metabolic equivalent of task (MET)-h·week⁻¹, those with <7.5 MET-h·week⁻¹ had a 2.24-fold increased risk of sarcopenia (OR=2.24, 95%CI: 1.17, 4.29). The RCS results found that LPA duration and total physical activity volume each showed a nonlinear dose-response relationship with the risk of sarcopenia (P_overall<0.05, P_non-linear<0.05). Compared with the elderly with an LPA duration of 0 h· week⁻¹, the risk of sarcopenia in the elderly with an LPA duration of 12.6 h· week⁻¹ was the lowest (OR=0.42, 95%CI: 0.21, 0.83). Compared with the elderly with a total physical activity volume of 15.0 MET-h· week⁻¹, the elderly with a total physical activity volume of 46.0 MET-h· week⁻¹ had the lowest risk of sarcopenia (OR=0.57, 95%CI: 0.38, 0.84). There was no statistically significant association between weekly MVPA duration and the risk of sarcopenia (P>0.05). Conclusion Increasing weekly LPA duration and total physical activity volume would help to reduce the risk of sarcopenia.

Objective　To understand the serotypes and sources of dengue virus (DENV) in Yunnan Province in 2023, providing a scientific basis for dengue fever prevention and control. Methods DENV nucleic acid testing and virus isolation were performed on the serum samples of dengue fever cases diagnosed at three national monitoring sites in Yunnan Province (Longchuan County, Menghai County, Hekou County) in 2023. Dengue virus envelope (E) gene sequencing was performed on positive serum samples and dengue virus isolates, and phylogenetic analysis was conducted using molecular biology software. Results A total of 1 006 dengue fever cases were reported at three monitoring sites in 2023, including 838 imported cases, 161 cases imported from other counties and cities in Yunnan, and 7 autochthonous cases. Among 371 serum samples, 351 were found DENV-positive, including 305 DENV-1 positive samples (174 imported from Myanmar, 1 imported from Laos, 1 imported from Vietnam, 99 imported from Jinghong, 26 imported from Ruili, and 4 local cases), 43 DENV-2 positive samples (8 imported from Myanmar, 6 imported from Jinghong, 26 imported from Ruili, and 3 local cases), 1 DENV-3 positive sample (imported from Myanmar), 1 DENV-4 positive sample (introduced from Ruili), and 1 untyped case. A total of 23 DENV strains were isolated, including 9 strains of DENV-1, 12 strains of DENV-2, 1 strain of DENV-3, and 1 strain of DENV-4. All DENV-1 strains from three monitoring sites belong to genotype I but were located on different evolutionary branches. The DENV-2 strains from Menghai County and Longchuan County belonged to the Cosmopolitan genotype and Asian I genotype, respectively. The DENV-3 strain from Longchuan County belonged to genotype I, and the DENV-4 strain from Longchuan County belonged to genotype I. Conclusions During the dengue fever epidemic season, the border regions of Yunnan Province face dual pressures from both international and domestic imported dengue cases. Imported or introduced cases carried DENVs of serotypes 1-4 (with five genotypes in total), leading to local outbreaks caused by these cases. Imported and local DENVs originated from Southeast Asian countries and exhibited distinct geographic distribution characteristics.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To analyze the hot spots,rules and distribution on safety research of inhalation preparations at home and abroad in the past 20 years,and to summarize the current status of safety and risk control research on inhalation preparations.Methods This reaserch is based on the literature related to the safety and risk control of inhalation preparations in the core collection database of the Web of Science.With the help of Excel 2021 and CiteSpace6.1.R3,visualized processing and analysis were carried out on the annual number of publications,countries,institutions,authors,co-occurrence of keywords,clustering and prominence.Results A total of 365 articles were included,the annual publication number in the field of the safety and risk control of inhalation preparations was less than 30 per year from 2002 to 2018.But since 2019,the number of articles published this year has exceeded 30.Through the analysis of the cooperation network of countries and institutions,the top four countries in terms of publication volume are the United States,the United Kingdom,Germany,and China,and the top three institutions are AstraZeneca,GlaxoSmithKline and Pfizer.Through the analysis of the author cooperation network,the cooperation network between European and American authors was formed earlier,and a certain research group has appeared in 2002.In contrast,a more concentrated cooperation network has been formed in China in 2020.Conclusions In the past 20 years,the research on inhalation preparations has mainly focused on their safety and efficacy,while there are few studies on their risk control.There is a disconnect between safety assessment and risk assessment,and the future focus maybe focused on the adverse reaction assessment and risk management research of inhalation preparations.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Objective To evaluate the clinical efficacy and safety of modified Weijing Decoction in the treatment of stable stage of bronchiectasis(phlegm heat accumulating in the lung pattern).Methods A series of N-of-1 trials using bronchiectasis patients in stable stage with phlegm heat accumulation in the lung pattern were performed.Participants meeting inclusion criteria underwent two distinct treatment protocols during a therapy period.Modified Weijing Decoction was used in the experimental period and ambroxol tablets were used in the control period,washout periods were set.The medication-use order in the control period and experimental period is random.The visual analog scale(VAS)was used to assess symptom changes before and after treatment.24-hour sputum volume and COPD self-assessment test(CAT)scores were recorded,while adverse reactions were monitored during the study period.Statistical analysis and drawing were performed on SPSS 25.0 and GraphPad Prism 8.Comparison of inter-group differences before grouping was assessed by independent samples t-test.Analysis of symptom score,24-hour sputum volume and CAT scores in the experimental and control periods,as well as comparison of differences between the above two groups before and after treatment were performed using paired t-test,which enabled comprehensive exploration of clinical and statistical distinctions.Results A total of 9 patients participated in 16 rounds of analysis.Statistically significant differences(P＜0.05)before and after the treatment in the experimental period were noted in total Traditional Chinese Medicine(TCM)symptom scores,cough,sputum,sputum color,chest tightness and chest pain,bitter and dry mouth,fatigue and tiredness,24-hour sputum volume,and CAT score.Paired t-tests revealed significant variations(P＜0.05)in the total TCM symptom scores,sputum color scores,scores of chest tightness and pain,and 24-hour sputum volume between experimental and control periods.No adverse events related to the test methods or drugs occurred during the observation period.Conclusion Modified Weijing Decoction could comprehensively improve clinical symptoms of bronchiectasis patients in stable stage.It exhibits superior efficacy compared to ambroxol,and maintains a favorable safety profile.

Objective:To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics.Methods:A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline.Results:(1) CO ( r=0.155, P<0.001), TFC ( r=0.338, P<0.001), MAP ( r=0.204, P<0.001), and HR ( r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation ( r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age ( r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR ( P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy ( P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions:The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

Objective:To evaluate the impact of bladder volume on dosimetric parameters of clinical target volume (CTV) and organs at risk (OAR) of intensity modulated proton therapy (IMPT) for localized prostate cancer during the treatment planning and daily treatment.Methods:Clinical data of 25 patients with localized prostate cancer admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to June 2022 and enrolled in the "Proton Therapy System" (SAPT-PS-01) registered clinical trial were retrospectively analyzed. All patients were male and the median age was 72 years old. A total of 30 sets of IMPT plans were obtained. Based on the planning CT (30 sets) and weekly verification CT during treatment (172 sets), bladder volume, CTV and OAR dose parameters were collected. Spearman correlation analysis was used to evaluate the correlation between bladder volume in CT and the dosimetric parameters of CTV and OAR during IMPT plans, and Wilcoxon-Mann-Whitney test was adopted to compare the dosimetric parameters of CTV and OAR among different bladder volume change groups.Results:The V 95% of CTV1 and CTV2 were both 100.0%±0.0% in IMPT plans. Bladder volume was significantly negatively correlated with D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE) of the bladder ( P<0.001, 0.003, <0.001, <0.001,<0.001), and D mean, V 50 Gy(RBE) of the small intestine (both P<0.001). During treatment, bladder D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE)( P<0.001, 0.001, <0.001, <0.001, <0.001), rectal D mean, V 50 Gy(RBE), V 40 Gy(RBE) (all P<0.001), small intestine D mean, V 50 Gy (RBE) (both P<0.001) of patients with bladder volume increase >20% compared to baseline were significantly decreased compared to those in IMPT plans. But CTV1 V 100%, and CTV2 V 95% were significantly decreased too( P=0.029, 0.020). In the bladder volume decreased>20% patients, the D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE) of the bladder were significantly increased compared to those in IMPT plans (all P<0.001). However, a bladder volume reduction of ≤20% and increase of ≤20% from baseline had no significant impact on CTV and OAR dosimetric parameters during treatment. Conclusions:For patients with localized prostate cancer undergoing proton therapy, a certain bladder volume should be ensured during planning CT scans. During the daily treatment, the bladder volume should be maintained between 80%-120% of the baseline level to ensure CTV coverage and good dose sparing to OAR.

ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii （CRAB） nosocomial infection in an intensive care unit （ICU） and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing （MLST） were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified， among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance， and were all classified into ST368 type. In the surface and hand samples （n=40）， 2 CRAB strains were detected in the air filter beside the bed of the first case， with a detection rate of 5%. After adopting comprehensive prevention and control strategies， including environmental cleaning and disinfection， hand hygiene， staff management and training， and supervision， no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection， and inadequate implementation of hand hygiene. Timely identification， investigation， and targeted measures remain crucial to effective control of possible nosocomial infection.