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.

Objective:To evaluate clinical efficacy of Xuanbai Chengqi Decoction in the treatment of severe pneumonia with gastrointestinal dysfunction of syndrome of lung heat and fu-organ excess; To discuss its effects on short chain fatty acid (SCFA)/G protein coupled receptor 43 (GPR43) axis.Methods:It was a randomized controlled trial. From January 2020 to January 2022, 60 hospitalized patients with severe pneumonia complicated with gastrointestinal dysfunction (syndrome of lung heat and fu-organ excess) in the Intensive Care Department and Emergency Intensive Care Unit of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine were selected as the observation subjects. They were divided into experimental group and control group according to random number table method, with 30 cases in each group. Patients in the control group were treated with conventional Western medicine, while patients in the experimental group received Xuanbai Chengqi Decoction combined with conventional Western medicine. Both groups were treated continuously for 7 days and followed up for 28 days. TCM syndrome scores were evaluated before and after treatment. Clinical Pulmonary Infection Score (CPIS) was used to assess pulmonary infection, Gastrointestinal Dysfunction Score (GIDS) was used to assess the degree of gastrointestinal dysfunction, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was used to assess the prognosis. ELISA was used to detect levels of procalcitonin (PCT), IL-6, CRP, D-lactate (D-LA), short chain fatty acids (SCFA), and G protein coupled receptor 43 (GPR43). The fully automated blood analyzer (flow cytometry) was used to detect white blood cells (WBC) and the proportion of neutrophils (N%). Indirect bladder pressure measurement method was used to measure the intra-abdominal pressure of patients. During treatment, the adverse reactions or events were recorded. Patients were followed up for 28 days and the 28-day mortality rate was recorded.Results:The total effective rate was 73.33% (22/30) in the experimental group and 40.00% (12/30) in the control group, with statistical significance ( χ2=6.79, P<0.05). After treatment, TCM syndrome scores, CPIS, GIDS, and APACHEⅡ score in the experimental group were lower than those in the control group ( t values were 2.84，3.34，2.75，3.05，respectively， P<0.01), serum PCT [(0.35 ± 0.11) μg/L vs. (0.64 ± 0.10) μg/L, t=2.45], IL-6 [(19.33 ± 3.54) ng/L vs. (60.13 ± 15.01) ng/L, t=2.98], N% [(78.84 ± 2.09)% vs. (83.30±2.31)%, t=3.43], and CRP [(28.43 ± 6.38) mg/L vs. (54.48 ± 9.03) mg/L, t=4.02], intra-abdominal pressure [(9.11 ± 2.55) mmHg vs.(11.70 ± 3.02) mmHg, t=7.78] and D-LA [(0.11±0.05) mmol/L vs. (0.18±0.12) mmol/L, t=6.45] in the experimental group were lower than those in the control group ( P<0.05 or P<0.01). After treatment, serum SCFA [(48.18 ± 36.31) μmol/L vs. (35.10 ± 19.32)μmol/L, t=1.95] and GPR43 [(1 254.61 ± 437.40) ng/L vs. (990.15 ± 403.03) ng/L, t=2.13] in the experimental group were higher than those in the control group ( P<0.05). The 28-day mortality rates of the experimental group and the control group were 20.00% (6/30) and 46.67% (14/30) respectively, with statistical significance ( χ2=4.80, P<0.05). During the trial, there were no serious adverse reactions or adverse events in either group. Conclusion:Xuanbai Chengqi Decoction can effectively treat severe pneumonia complicated with gastrointestinal dysfunction. The mechanism may involve the up-regulation of SCFA/GPR43 axis.

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 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 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.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

Objective To analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.

Objective To observe the ultrasonic manifestations and possible etiology of fetal tricuspid regurgitation(TR).Methods Totally 717 fetuses diagnosed with TR by prenatal ultrasound were retrospectively enrolled,and the prenatal ultrasonic findings were observed.Based on postpartum follow-up data,the fetuses were divided into physiological TR group(n=468)and pathological TR group(n=249),and those in the latter were further divided into right heart preload increase subgroup(n=76),right heart afterload increase subgroup(n=127)and tricuspid valve structure abnormality subgroup(n=46)according to the possible etiology,and the ultrasonic manifestations were comparatively analyzed.Results In physiological TR group,mild and moderate TR was found in 441(441/468,94.23％)and 27 fetuses(27/468,5.77％),respectively,while no severe TR was noticed.In pathological TR group,significant difference of TR degrees was found among 3 subgroups(x2=37.244,P＜0.001).Mild TR was more common in right heart preload increase subgroup,while moderate and severe TR were more common in the other 2 subgroups.In right heart preload increase subgroup,fetuses with persistent left superior vena cava were more likely to develop mild TR,while those with intact interventricular septum and pulmonary artery occlusion were more likely to develop severe TR in right heart afterload increase subgroup(both P＜0.05).No significant difference of TR degree was found among fetuses with different possible etiology in right heart preload increase subgroup nor right heart afterload increase subgroup(both P＞0.05).In tricuspid valve structure abnormality subgroup,significant differences of TR degrees were found among fetuses with different possible etiologies(P＜0.05),and fetuses with underdeveloped tricuspid valve were more prone to severe reflux(P＜0.05).There were significant differences of reflux velocity of moderate and severe TR among 3 subgroups(F=6.945,P=0.002).Conclusion Fetal TR was mostly physiological.The possible etiologies of pathological TR were variable,including pulmonary valve stenosis,persistent left superior vena cava and tricuspid valve hypoplasia,with different prenatal ultrasonic manifestations.