Sepsis remains a challenge in critical care worldwide，with intestinal microbiome dysbiosis implicated in its onset，progression，and organ dysfunction. Germ-free （GF） and human microbiota-colonized animals，by eliminating confounding from resident microbiota and combining induction methods such as CLP/LPS/live-bacterial challenge with fecal microbiota transplantation （FMT） and mono- or combined colonization，enable causal tests and dissection of microbiota-host interactions and drug mechanisms. This review summarizes the application of GF and related models in sepsis research. At the immune level，TLR-related signaling and pathogen community-induced suppression of IRF3-dependent defense affect innate immunity and pathogen clearance. At the barrier level，reprogramming of tight junction proteins and increased permeability drive gut-derived amplification. At the metabolic level，short-chain fatty acids and bile acids function as metabolic valves influencing GPR/HDAC signaling. At the epigenetic level，EZH2 and histone deacetylation emerge as druggable targets. We further synthesize anti-sepsis evidence for traditional Chinese medicine （TCM），mainly from conventional animals and clinical studies，discussing how formulae （e.g.，Xuebijing，Shenfu，and Huanglian Jiedu Tang） and active constituents （e.g.，berberine，luteolin，ginsenosides，and resveratrol） may act through microbiota-related and direct host pathways，with FMT/metabolite replenishment enabling further causal testing. Finally，we propose a closed-loop GF-humanized-clinical stratification paradigm for integrated evaluation of microecology，epigenetics，immunity，and organ outcomes，providing a translational path for precision prevention and treatment based on TCM and the microbiome.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Objective The imaging findings of X-ray defecography(XRD)and magnetic resonance defecog-raphy(MRD)of patients with Solitary Rectal Ulcer syndrome(SRUS)were retrospectively analyzed to provide important information for clinical diagnosis and treatment.Methods 19 patients with SRUS confirmed by clinical,pathological and colonoscopy were included in this study.Among them,15 patients underwent XRD and 7 patients underwent MRD,and 3 patients underwent both XRD and MRD.Data of all enrolled patients were collected and pelvic floor function was measured.Results In the results of XRD,3 patients(20%)showed rectal intussusception.8 patients(53.3%)showed external rectal prolapse and 2 patients(13.3%)showed moderate rectocele.In addition,there were 2 patients of puborectal muscle hypertrophy,and 1 patient of bladder prolapse and uterine prolapse,respectively.For MRD,3 patients(42.9%)showed rectal mucosal prolapse(partial prolapse).At 4 patients(57.1%)with rectocele,3 patients(all female)had moderate rectocele,1 patient had mild rectocele.3 patients were also observed related anterior and middle compartment organ descent.2 patients of pubulorectal muscle hypertrophy,no sigmoidocoele.Conclusion Defecography can evaluate the structural and functional abnormalities of pelvic floor in SRUS patients,such as external rectal prolapse,rectal protrusion,rectal mucosal prolapse,and rectal intussusception,which has guiding significance for the treatment of SRUS patients.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.