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 observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

Purpose To investigate the expression of fuma-rate hydratase(FH)and 2-succinocysteine(2SC)in leiomyoma with singular nuclear features,and to analyze the diagnostic val-ue of these two proteins in fumarase hydratase-deficient(FH-d)uterine leiomyomas.Methods Sixty-seven cases of leiomyoma with singular nuclear features were collected.The expression was detected by immunohistochemical EnVision method,and the relationship between the expression of FH,2SC and the morpho-logical characteristics of FH-d uterine leiomyomas was analyzed,and the relevant literature was reviewed.Results There were 67 patients of leiomyoma with singular nuclear features,among which 27 had FH-d leiomyoma.The positive rate of FH was(2/27,7.41％),significantly lower than that of leiomyomas without FH-d(31/40,77.50％).The positive rate of 2SC(26/27,96.30％)was significantly higher than that of leiomyo-mas without FH-d(11/40,27.50％).The statistical results showed that there was a correlation between the expression of FH and 2SC(P＜0.05);positive expression of FH and 2SC was associated with significant eosinophilic nucleoli,perinucleolar vacuoles,eosinophilic inclusions and antler vessels(P＜0.05).The sensitivity and specificity of FH immunohistochemi-cal identification of FH defective leiomyoma were 92.59％and 77.50％,respectively.The sensitivity and specificity of 2SC immunohistochemical were 96.30％and 72.50％for FH defec-tive leiomyomas,respectively.Conclusion In most leiomyomas with FH-d morphology,FH expression is negative and 2SC ex-pression is positive.The combined detection of FH and 2SC can significantly improve the diagnosis of FH defective leiomyoma.

Objective To explore the construction of modular intervention for patients dependent on mechanical ventilation in ICU,and to conduct the clinical empirical study.Methods A total of 100 mechanical ventilation-dependent patients in ICU were enrolled and divided into two groups according to the admission order,with 50 patients in each group.Control group received routine intervention,while observation group was treated with modular intervention in addition to the treatment given to control group.The weaning success rate,weaning time,complications,rehabilitation index,blood gas analysis index,psychological state,and nutritional status were compared between two groups.Results Compared with control group,observation group had higher weaning success rate,shorter weaning time,ICU stay and general ward admission,and lower incidence of complications(P<0.05).After intervention,observation group had lower PaCO2,and higher PaO2 and PaO2/FiO2 than control group(P<0.05);the scores of SAS,SDS and APACHEⅡwere lower in observation group than in control group(P<0.05);and the serum levels of ALB,PA,TRF and TP in observation group were higher than those in control group(P<0.05).Conclusion Modular intervention for mechanical ventilation-dependent patients in ICU can increase weaning success rate,improve blood gas analysis index and nutritional status,alleviate negative emotions,reduce complications and speed recovery.

Objective:To construct an evaluation index system for the core competence of hospital specialist service operation assistants and provide reference for the evaluation of such competence.Methods:From January to March 2022, literature analysis and behavioral event interviews were used to initially establish a core competence evaluation index system of hospital specialist service operation assistants, based on the Donabedian model. Subsequently, the Delphi expert consultation method was applied to conduct correspondence consultation, inviting experts to evaluate the contents and importance of the index system, using analytic hierarchy process to determine the weights of the indexes at all levels.Results:Two rounds of expert consultation were carried out, and the valid recovery rate of the questionnaire was 100%. The familiarity coefficient of the second round of correspondence was 0.87, the basis of judgment coefficient was 0.90, and the authority coefficient was 0.89. The final evaluation index system for core competence of hospital specialist service operation assistant consisted of 3 first-level indexes, 13 second-level indexes and 81 third-level indexes. The weight of the first-level index structure index was 0.266, and the highest weight among the second-level indexes was the operational development ability (0.083), while the highest weight among the third-level indexes of operational development ability was the comprehensive coordination ability (0.193); The weight of the first-level index process index was 0.405, and the corresponding second-level and third-level indexes with the highest weight were department operation practice work (0.157) and reasonable resource allocation (0.303), respectively; The weight of the first-level index result index was 0.329, and the corresponding second-level and third-level indexes with the highest weight were the weight of medical quality and safety (0.103) and drug adverse reaction reporting rate (0.237), respectively.Conclusions:The evaluation index system constructed in this study proves scientific and reasonable in weight assignment, proving a reference for the management of the specialist service operation assistants.

In China, the level of ambient fine particulate matter (PM 2.5 ) pollution far exceeds the air quality standards recommended by the World Health Organization. Moreover, the health effects of PM 2.5 exposure have become a major public health issue. More than half of PM 2.5 -related excess deaths are caused by cardiopulmonary disease, which has become a major health risk associated with PM 2.5 pollution. In this review, we discussed the latest epidemiological advances relating to the health effects of PM 2.5 on cardiopulmonary diseases in China, including studies relating to the effects of PM 2.5 on mortality, morbidity, and risk factors for cardiovascular and respiratory diseases. These data provided important evidence to highlight the cardiopulmonary risk associated with PM 2.5 across the world. In the future, further studies need to be carried out to investigate the specific relationship between the constituents and sources of PM 2.5 and cardiopulmonary disease. These studies provided scientific evidence for precise reduction measurement of pollution sources and public health risks. It is also necessary to identify effective biomarkers and elucidate the biological mechanisms and pathways involved; this may help us to take steps to reduce PM 2.5 pollution and reduce the incidence of cardiopulmonary disease.
Humans ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Risk Factors ; Respiratory Tract Diseases ; China/epidemiology* ; Environmental Exposure/adverse effects*

Objective:To investigate the effect and mechanism of the Bushen Jianpi Kaixin formula on the learning and memory ability of Alzheimer's disease (AD) model rats.Method:A total of 72 SPF grade male SD rats were divided into control group, model group, Bushen group, Jianpi group, Kaixin group and Bushen Jianpi Kaixin group according to the random number table method ( n=12 in each group). The rats were intraperitoneally injected with D-galactose once a day for 6 weeks to replicate the model of AD.And the rats in different medication groups were given corresponding administration (Bushen formula: gavage 3.60 g·kg -1·d -1, Jianpi formula: gavage 4.05 g·kg -1·d -1, Kaixin formula: gavage 2.34 g·kg -1·d -1, Bushen Jianpi Kaixin formula: gavage 9.99 g·kg -1·d -1), while rats in control group and model group were treated with equal volume of 0.9% sodium chloride solution once a day for 28 days.The learning and memory ability was tested by Morris water maze.The expressions of phosphoinositide 3-kinase(PI3K), protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in cerebral cortical tissues were detected by immunohistochemistry.The relative mRNA levels of p62 and Beclin in brain cortical tissue were detected by RT-PCR.SPSS 25.0 software was used for data processing, one-way ANOVA was used for inter group comparisons, and LSD test was used for further pairwise comparisons. Results:Morris water maze results showed statistically significant differences in escape latency and the times of crossing platform among the six groups ( F=368.10, 47.43, both P<0.01). The escape latency of Bushen Jianpi Kaixin group((29.30±1.64) s) was shorter than that of model group((55.58±3.23) s) ( P<0.01), the times of crossing platform ((5.17±0.72) times) in Bushen Jianpi Kaixin group was higher than that of model group (1.50±0.52)time, P<0.01). Compared with the Bushen Jianpi Kaixin group, the escape latencies of Bushen group, Jianpi group and Kaixin group were longer (all P<0.01), the times of crossing platform in Bushen group was lower ( P<0.01). Immunohistochemical results showed statistically significant differences in the positive protein expression of PI3K, Akt, and mTOR proteins among the six groups ( F=68.52, 22.22, 31.52, all P<0.01). Compared with the model group, the levels of positive protein of PI3K ((0.47±0.15), (0.57±0.12)), Akt ((0.31±0.02), (0.38±0.02)), and mTOR ((0.22±0.18), (0.28±0.11)) in Bushen Jianpi Kaixin group were less (all P<0.01). Compared with the Bushen Jianpi Kaixin group, the levels of positive protein of PI3K and mTOR of Bushen group, Jianpi group and Kaixin group were higher (all P<0.01). RT-PCR results showed statistically significant differences in the relative mRNA levels of Beclin and p62 among all the groups ( F=8.79, 21.01, both P<0.01). The relative mRNA level of Beclin in Bushen Jianpi Kaixin group was higher than that of the model group ((0.97±0.07), (0.64±0.12)), and the relative mRNA level of p62 of Bushen Jianpi Kaixin group was less than that of model group((0.98±0.16), (1.16±0.24))(both P<0.01). The relative mRNA levels of p62 in Bushen group, Jianpi group and Kaixin group were higer than those of Bushen Jianpi Kaixin group (all P<0.05). Conclusion:Bushen Jianpi Kaixin formula can improve cognitive impairment and learning and memory ability in AD model rats.The mechanism may be related to the regulation of PI3K/Akt/mTOR autophagy pathway.The combination prescription is better than the split prescription.