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.

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.

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.

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.

ObjectiveTo investigate the etiology and epidemiological characteristics of pneumonia in children of different ages, to better characterize the co-infection patterns of pneumonia and their association with severe diseases. MethodsChildren aged 28 days to 13 years with pneumonia who were hospitalized in the Department of Pediatrics, Dongyang People's Hospital, Zhejiang Province from April 1 to December 28, 2023 were selected as the research subjects. Oropharynx swabs were collected from the patients within 24 hours of hospital admission, and PCR tests were conducted for 18 respiratory pathogens. Binary multivariate logistic regression analysis was used to analyze the status of viral and bacterial infection, patterns of co-infection in patients with different ages, and the risk factors for the outcome of severe pneumonia. ResultsA total of 2 191 hospitalized children with pneumonia were enrolled in the study. Severe cases were more common in children aged 5 years and older (53.3%) and in the second quarter of the year (46.5%). An average of (1.31±0.90) pathogens were detected in severe cases. Mycoplasma pneumoniae (44.4%, 973 cases) had the highest detection rate of pathogens. Streptococcus pneumoniae (21.7%, 476 cases) and rhinovirus (10.1%, 222 cases) were the most common bacteria and viruses, respectively, in hospitalized children with pneumonia in Dongyang City. Multivariate logistic regression analysis indicated positive interactions between different viral and bacterial pathogens. The adjusted OR (aOR) values for different respiratory pathogens in children with severe pneumonia varied significantly (all P<0.04). Among them, Chlamydia pneumoniae (aOR=9.74, 95%CI=2.36‒49.32, P<0.01), Mycoplasma pneumoniae (aOR=2.62, 95%CI=2.04‒3.37, P<0.01), and RSV (aOR=1.69, 95%CI=1.12‒2.54, P<0.01) were the risk factors for severe pneumonia. ConclusionIn the pathogen spectrum of children with pneumonia in Dongyang City, Zhejiang Province from April to December 2023, most viruses and bacteria exhibited positive interactions. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV maybe the significant risk factors for severe pneumonia.

Objective: To analyze the HIV detection results through different detection routes in Jiading District, Shanghai Municipality from 2009 to 2023, so as to provide the reference for improving HIV detection measures. Methods: Data pertaining to HIV detection in Jiading District from 2009 to 2023 was collected through the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The number of HIV detection and HIV positive rates through detection routes including voluntary counseling and testing (VCT) clinics, sexually transmitted disease (STD) clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were described. Results: A total of 1 729 347 HIV tests were conducted in Jiading District from 2009 to 2023, with an average annual growth rate of 7.55%. A total of 1 125 HIV positive cases were confirmed, with an HIV positive rate of 6.51/104. The number of HIV detection conducted in VCT clinics, STD clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were 11 516, 112 880, 692 609, 635 770, 196 315 and 80 257, respectively. The main detection routes were pre-operation and blood transfusion (products) as well as premarital and antenatal periods, accounting for 40.05% and 36.76%, respectively. The HIV positive rates in VCT clinics, STD clinics, pre-operation and blood transfusion (products), premarital and antenatal periods, other clinical outpatients and other populations were 336.05/104, 21.79/104, 2.93/104, 0.35/104, 10.95/104 and 6.48/104, respectively. The HIV positive rate in VCT clinics was higher than that in other detection routes (all P<0.001). Conclusions From 2009 to 2023, the number of HIV tests increased in Jiading District, mainly through pre-operation and blood transfusion (products) as well as premarital and antenatal periods. The HIV positive rate was the highest in VCT clinics.

Objective:To investigate the clinical efficacy of arthroscopic double-row double-pulley technique in the treatment of Ideberg type IA scapular glenoid fracture.Methods:A retrospective case series study was conducted to analyze the clinical data of 16 patients with Ideberg type IA scapular glenoid fracture admitted to Jiading Branch of Shanghai General Hospital from January 2018 to December 2021, including 10 males and 6 females, aged 25-65 years [(42.9±5.1)years]. The patients were treated with arthroscope-assisted reduction and double-row double-pulley technique. The operation time was recorded. Three-dimensional reconstruction of the shoulder joint with CT was performed to assess fracture displacement and healing. Modified University of California Los Angeles (UCLA) score and Constant-Murley score were used to evaluate shoulder function and Visual Analogue Scale (VAS) score was used to evaluate pain before surgery, at 3, 6, 12 months after surgery and at the last follow-up. The complications were observed.Results:All the patients were followed up for 12-36 months [(20.3±4.4)months]. The operation time was 60-90 minutes [(74.7±8.9)minutes]. Three-dimensional construction of the shoulder joint with CT performed at 3 months after surgery showed that there was no fracture re-displacement and all the patients had bone union. The modified UCLA score, Constant-Murley score and VAS score at 3 months after surgery were (30.4±0.4)points, (84.3±1.4)points and 2.0(1.3, 3.0)points, respectively, which were significantly improved compared with those before surgery [(21.1±0.5)points, (56.4±1.3)points and 5.0(5.0, 6.0)points respectively] ( P<0.05). The modified UCLA score, Constant-Murley score and VAS score at 6 months after surgery were (33.1±0.4)points, (91.0±0.5)points and 1.0(1.0, 2.0)]points respectively, which were significantly improved compared with those at 3 months after surgery ( P<0.05). The modified UCLA score, Constant-Murley score and VAS score at 12 months after surgery were (33.5±0.3)points, (92.6±0.6)points and 1.0(0.3, 1.8)points respectively, showing no significant differences from those at 6 months after surgery ( P>0.05). The modified UCLA score, Constant-Murley score and VAS score at the last follow-up were (33.8±0.8)points, (93.7±1.8)points and 1.0(0.0, 1.0)points respectively, with no significant differences from those at 12 months after surgery ( P>0.05). There were no complications such as wound infection, neurovascular injury or shoulder stiffness after surgery. Conclusion:Arthroscopic double-row double-pulley technique for the treatment of Ideberg type IA scapular glenoid fracture has a short operation time, a high fracture healing rate, good shoulder function recovery, and pain relief, with no common complications.