Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Objective: To explore the influencing factors of recurrence in postoperative patients with renal cell carcinoma，construct machine learning prediction models and evaluate their performance. Methods: Clinical data of 915 patients with renal cell carcinoma treated in our hospital during 2013 and 2021 were retrospectively collected.The data were randomly divided into a training set (n=510) and a validation set (n=218) in a 7∶3 ratio.In the training set，LASSO regression algorithm was used to screen important variables，and machine learning prediction models were constructed to predict the recurrence risk.In the validation set，the effectiveness of the models was compared combined with the area under receiver operating characteristic curve (AUC)，accuracy rate，F1 value and other indicators. Results: LASSO regression screened out the risk factors，including smoking history，tumor size，N stage，Fuhrman grade，thrombin time and fibrinogen，based on which，the logistic model，decision tree model，random forest model，and Bayes model were constructed.In the validation set，the AUC of the above 4 models was 0.862，0.792，0.843 and 0.861，respectively; the accuracy was 0.917，0.908，0.904 and 0.927，respectively; F1 value was 0.357，0.286，0.323 and 0.600，respectively.The Bayes model had the most stable performance and best differentiation. Conclusion: In this data set，the prediction model based on Bayes algorithm has a good performance and can provide reference for clinical decision making.

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

ObjectiveTo describe the characteristics of the nasopharyngeal microbiota in children under 5 years of age in Haidong City, Qinghai Province and analyze its associated factors, so as to provide basic data for the evolution and development of nasopharyngeal microbiota in children. MethodsA total of 230 community children from Haidong City, Qinghai Province were included in the study. Participants’ basic information was collected by local volunteers from parents/guardians at enrollment. 16S rDNA sequencing was used to identify the bacterial diversity and abundance of nasopharyngeal microbial community. Bioinformatics methods were used to analyze the characteristics of the nasopharyngeal microbiota, compare the differential species, and investigate the correlation with age. ResultsThere was no statistical difference in either Chao1 index or Shannon index of nasopharyngeal microbial communities among children with different ages (P>0.05). Besides, the structure of nasopharyngeal microbiota in children of different ages was different, either (P=0.020). Age, ethnicity and delivery mode, to some extent, could explain the differences in the structure of nasopharyngeal microbiota in children. There were statistically significant differences in the abundance of Dolosigranulum, Staphylococcus and Corynebacterium in the nasopharyngeal microbiota of children with different ages (P<0.05). Differential analysis revealed that Corynebacterium was found to be over-represented in children under 1 year of age, while Dolosigranulum was found to be over-represented in children between 2 and 3 years old. Furthermore, the results of correlation analysis showed that, Moraxella was positively correlated with Corynebacterium, Dolosigranulum and Streptococcus, but negatively correlated with Pseudomonas. In addition, a strong positive correlation was detected between the Dolosigranulum and Corynebacterium. ConclusionThe diversity of nasopharyngeal microbial community among children under 5 years in Haidong City, Qinghai Province is stable. However, there are differences in the species structure, mainly in the abundance difference of Dolosigranulum, Staphylococcus and Corynebacterium. This study provides basic data on the evolution and maturation of nasopharyngeal microbial communities in early childhood, which can provide a scientific basis for the early prevention and diagnosis of respiratory tract infections in children.

Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology* ; Autophagy/physiology* ; Humans ; Muscle, Skeletal/pathology* ; Mitophagy ; Animals ; Mitochondria/metabolism* ; Lysosomes

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

Objective:To investigate the anti-fatigue effect of Dendrobium and Panax Quinquefolius Granules(DPQG)on the overtrained mice,and to clarify its possible mechanism.Methods:A total of 48 mice were randomly divided into control group(equal volume of distilled water),low dose of DPQG group(400 mg·kg-1 DPQG),medium dose of DPQG group(800 mg·kg-1 DPQG),and high dose of DPQG group(1 600 mg·kg-1 DPQG).The DPQG were administered by gavage for 35 d,and the rotarod test and swimming endurance test were performed 30 min after last administration.Serum,liver tissue,and muscle tissue were collected from the mice in various groups.ELISA method was used to detect the serum lacticacid(LAC)levels and lactate dehydrogenase(LDH)activities,and the malondialdehyde(MDA)levels,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities,and the liver glycogen and muscle glycogen levels in muscle tissue of the mice in various groups;HE staining was used to observe the pathomorphology of muscle tissue of the mice.Transcriptomics and metabolomics technologies were used to identify the key genes and metabolites in muscle tissue of the mice in control group and high dose of DPQG group and to analyze the correlations between differentially expressed genes(DEGs)and differentially expressed metabolites.Results:Compared with control group,the rod turning exhaustion time of the mice in different doses of DPQG groups were significantly increased(P＜0.05),and the swimming exhaution time of the mice in high dose of DPQG group was increased(P＜0.05).Compared with control group,the LDH,SOD,and GSH-Px activities of the mice in medium and high doses of DPQG groups were increased(P＜0.01).Compared with control group,the levels of MDA and liver glycogen of the mice in medium and high doses of DPQG groups were decreased(P＜0.05 or P＜0.01).The transcriptomics sequencing results showed that DPQG mainly acted on DEGs such as Trib3 and Olfr495;the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in olfactory-related processes and signaling pathways;the metabolomics KEGG analysis results showed that the differential metabolites were mainly enriched in the regulation pathway of inflammatory mediators on tryptophan(TRP);the combined analysis of transcriptomics and metabolomics results showed that the piezo1 gene had high correlations with the differential metabolites β1-solamarine(r=-1,P＜0.05)and tilidine(r=1,P＜0.05).Conclusion:DPQG can exert an anti-fatigue effect on the overtrained mice by modulating LAC metabolism and glycogen homeostasis,as well as maintaining the oxidative/antioxidant balance in the body;its anti-fatigue mechanism is related to the Olfr495 and piezo1 genes and the regulation pathway of inflammatory mediators on TRP channels.

Objective To systematically assess the spatiotemporal distribution,risk factors,and future trends of chronic obstructive pulmonary disease(COPD)among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease(GBD)data in order to provide support for the formulation of prevention and control strategies of the disease.Methods The GBD data from 1990 to 2021 were analyzed for the incidence,mortality,disability-adjusted life years(DALYs),and estimated annual percentage change(EAPC)of COPD in<50-year-old individuals across 204 countries and regions.The data were stratified by age,sex,region,country,and sociodemographic index(SDI).The COPD trends until 2035 were predicted.Results In 2021,the global incidence of early-onset COPD was estimated at 2.5 million cases(95%uncertainty interval:2.09～2.96 million),representing a 50.55%increase compared to 1990.Significant regional heterogeneity was observed,with low SDI regions experiencing a 134.08%increase,whereas high SDI regions exhibited a rise-then-fall trend.Risk factor analysis identified environmental and occupational exposures(air pollution,ambient ozone pollution,household air pollution from solid fuels,etc.)and smoking as the primary etiological factors.Notably,household solid fuel exposure accounted for 50.90%of COPD-related deaths in low SDI regions,compared to only 0.03%in high SDI regions.Projections indicated that by 2035,the global burden of early-onset COPD will increase to 2.59 million cases.Conclusion The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021,with pronounced disparities across regions and socioeconomic levels.COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution,and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.

ObjectiveTo investigate the current status and influencing factors of hand hygiene practices among primary healthcare workers， and to provide a reference for improving hand hygiene behavior in primary healthcare institutions. MethodsA self-designed questionnaire was used to conduct a survey among medical staff of seven community health service centers in Jiading District， Shanghai， using a cluster random sampling method. The data collected were subjected to descriptive statistics， reliability and validity tests， correlation analysis， and structural equation model fitting. ResultsA statistical difference in hand hygiene compliance was found among medical staff with varying occupational types and educational levels （P<0.05）， and medical staff in clinical departments exhibited higher levels of hand hygiene compliance （P<0.05）. In the health belief model， among the core variables， healthcare workers’ perceived benefits， perceived barriers， and self-efficacy had a direct impact on hand hygiene behavior， with direct effect values of 0.341， -0.152， and 0.234， respectively. Meanwhile， cues to action and perceived severity of COVID-19 infection indirectly affected hand hygiene behavior， with an indirect effect value of 0.066 and 0.062， respectively. ConclusionHealthcare workers generally exhibit a high degree of hand hygiene compliance， but there are variations in hand hygiene scores among healthcare workers with different characteristics. Enhancing healthcare worders’ perception of benefits， action cues， and self-efficacy while reducing perceived barriers can effectively improve their hand hygiene behavior.