ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

To understand the epidemiological characteristics and antimicrobial resistance of Esche-richia coli in free-range Tibetan pig populations,fecal samples from these pigs were collected be-tween 2021 and 2023 for pathogen isolation and identification.The isolated strains underwent anal-ysis of pathogenicity categories,phylogenetic grouping,and antimicrobial susceptibility profiles,a-long with resistance gene detection and mouse pathogenicity testing.The results showed that 123 strains of E.coli were isolated from 132 fecal samples.Enteropathogenicity tests revealed that 42.28％were EAEC(52/123),7.32％were EPEC(9/123),and 3.25％were STEC/EHEC(4/123).Phylogenetic analysis indicated that 78.86％(97/123)belonged to group A,while 11.38％(14/123)belonged to group B1.Antimicrobial susceptibility tests for 22 drugs showed the highest resistance rate to amoxicillin at 98.37％(121/123),followed by sulfamethoxazole at 73.98％(91/123).Resistance rates for ampicillin,tetracycline,erythromycin,and trimethoprim ranged from 48.78％to 51.22％.Furthermore,78.86％(97/123)of the isolates were resistant to three or more antibiotics.The detection of 52 drug-resistance genes in 10 categories showed that 15 drug-resist-ance genes were detected,and the detection rate was 28.85％(15/52).Among individual resistance genes,tetA had the highest detection rate at 63.41％(78/123),followed by tetB and qnrS with de-tection rates of 48.78％(60/123)and 38.21％(47/123),respectively.This study demonstrates that EAEC is the predominant strain of E.coli in free-range Tibetan pigs,with groups A and B1 being the major phylogenetic groups.The isolates exhibited a high degree of multidrug-resistant pheno-types,and the detection rates of resistance genes were also high.E.coli carrying virulence genes cause different degrees of pathological changes in the mouse ileum.The research results have sig-nificant public health implications and provide theoretical basis for the prevention,treatment,and clinical medication of E.coli disease in Tibetan pigs.

To understand the epidemiological characteristics and antimicrobial resistance of Esche-richia coli in free-range Tibetan pig populations,fecal samples from these pigs were collected be-tween 2021 and 2023 for pathogen isolation and identification.The isolated strains underwent anal-ysis of pathogenicity categories,phylogenetic grouping,and antimicrobial susceptibility profiles,a-long with resistance gene detection and mouse pathogenicity testing.The results showed that 123 strains of E.coli were isolated from 132 fecal samples.Enteropathogenicity tests revealed that 42.28％were EAEC(52/123),7.32％were EPEC(9/123),and 3.25％were STEC/EHEC(4/123).Phylogenetic analysis indicated that 78.86％(97/123)belonged to group A,while 11.38％(14/123)belonged to group B1.Antimicrobial susceptibility tests for 22 drugs showed the highest resistance rate to amoxicillin at 98.37％(121/123),followed by sulfamethoxazole at 73.98％(91/123).Resistance rates for ampicillin,tetracycline,erythromycin,and trimethoprim ranged from 48.78％to 51.22％.Furthermore,78.86％(97/123)of the isolates were resistant to three or more antibiotics.The detection of 52 drug-resistance genes in 10 categories showed that 15 drug-resist-ance genes were detected,and the detection rate was 28.85％(15/52).Among individual resistance genes,tetA had the highest detection rate at 63.41％(78/123),followed by tetB and qnrS with de-tection rates of 48.78％(60/123)and 38.21％(47/123),respectively.This study demonstrates that EAEC is the predominant strain of E.coli in free-range Tibetan pigs,with groups A and B1 being the major phylogenetic groups.The isolates exhibited a high degree of multidrug-resistant pheno-types,and the detection rates of resistance genes were also high.E.coli carrying virulence genes cause different degrees of pathological changes in the mouse ileum.The research results have sig-nificant public health implications and provide theoretical basis for the prevention,treatment,and clinical medication of E.coli disease in Tibetan pigs.

Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

Inflammatory bowel disease （IBD）， mainly including ulcerative colitis （UC） and Crohn's disease （CD）， is a common chronic inflammatory disease of the gastrointestinal tract， with its incidence increasing year by year. Due to its long treatment duration， difficulty in treatment， prolonged remission， and high costs， it has attracted global attention. Exploring safe， effective， and sustainable treatment regimens has become an urgent global issue. The pathogenesis of IBD is complex， involving intestinal mucosal injury，disturbances in the internal environment， and inflammatory responses. In recent years， research has found that ferroptosis is also one of the important pathogenic factors of IBD. Ferroptosis， as a new form of non-apoptotic cell death， is characterized by iron dependence， lipid peroxidation， and imbalance in the redox system. Studies have shown that inhibiting ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of IBD. IBD is mainly treated with drugs， including corticosteroids， aminosalicylates， biologics， and immunomodulators， but drug resistance and adverse reactions are common. Traditional Chinese medicine （TCM） has unique advantages such as low cost， low drug resistance， and fewer side effects， and has accumulated rich experience in the treatment of IBD. Scholars have confirmed that TCM can inhibit ferroptosis， and recent studies have shown that TCM can not only inhibit iron-dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa， thus playing a role in the treatment of IBD. Increasing evidence suggests that TCM may treat IBD by interfering with ferroptosis. This article explores the relevance of TCM intervention in ferroptosis and the treatment of IBD， discusses the possible mechanisms of ferroptosis in IBD， and aims to provide a basis for the diagnosis and treatment of IBD.

Objective As important components in the microenvironment of hepatocellular carcinoma(HCC),hepatic stellate cells(HSCs)and hydrogen sulfide(H2S)participate in various biological processes that regulate the development and progression of HCC.Through the co-culture of HSCs and HCC cells,this article aims to investigate the role and mechanism of HSCs in regulating the apoptosis of HCC cells by secreting H2S.Methods The HSC cell line(LX-2)and HCC cell lines(HepG2 and PLC/PRF/5)were used for experiment.RT-qPCR and Western Blot(WB)were used to measure the mRNA and protein expression levels of cystathionine γ-lyase(CSE),a key synthase for H2S;ELISA was used to measure the concentration of H2S in supernatant;next-generation sequencing,cell immunofluorescence assay,chromatin immunoprecipitation(ChIP),and WB were used to measure the JNK/JunB-TNFSF14 signaling pathway genes,binding sites,and related proteins after HepG2 cells were treated by H2S.LX-2 cells were co-cultured with HepG2 or PLC/PRF/5 cells in a Transwell chamber;CCK-8 assay and flow cytometry were used to measure the viability and apoptosis of HCC cells,and WB was used to measure the H2S-TNFSF14 signaling pathway-related proteins.All cell experiments were repeated three times.The independent-samples t test was used for comparison of continuous data between two groups;a one-way analysis of variance or the analysis of variance with repeated measures was used for comparison between multiple groups,and the Dunnett-t test was used for further comparison between two groups.Results LX-2 cells synthesized H2S mainly through CSE,and the concentration of H2S in supernatant of LX-2 cells gradually increased over time(22.89±0.08 pg/mL vs 28.29±0.15 pg/mL vs 36.19±1.90 pg/mL,F=79.63,P<0.05).In LX-2 cells,the mRNA expression level of CSE was significantly higher than that of CBS and MPST(1.008±0.13 vs 0.320±0.014 vs 0.05±0.02,F=80.84,P<0.05).When CSE was inhibited by PPG,the concentration of H2S decreased with the increase in the concentration of PPG(P<0.05).LX-2 cells were co-cultured with HepG2 or PLC/PRF/5 cells,and over the time of culture,there were significant reductions in the viability of HepG2 cells(87.48%±0.82%vs 70.48%±0.641%vs 52.89%±0.57%vs 45.20%±0.69%,F=1 517.13,P<0.001)and PLC/PRF/5 cells(92.41%±0.48%vs 74.10%±0.73%vs 53.70%±0.60%vs 44.00%±0.27%,F=2626.21,P<0.001)and significant increases in the apoptosis of HepG2 cells(12.88%±0.64%vs 15.5%±0.16%vs 18.43%±0.37%vs 13.01%±0.58%,F=142.15,P<0.001)and PLC/PRF/5 cells(8.51±0.05 vs 12.80±0.33 vs 15.59±0.21 vs 10.72±0.30,F=676.40,P<0.001),with the most significant changes on day 3.Next-generation sequencing showed that endogenous H2S and NaHS(endogenous H2S donor)were involved in regulating the expression of various genes in HepG2 cells.By releasing H2S,NaHS and LX2 activated the JNK/JunB signaling pathway and upregulated the expression of the apoptosis gene TNFSF14 in HCC cells,with increased binding between p-JunB and the transcriptional regulatory regions of the TNFSF14 gene.Conclusion In the microenvironment of HCC,HSCs activate the JNK/JunB signaling pathway in HCC cells through the signal molecules CSE/H2S,and there is an increase in the expression of TNFSF14,thereby promoting the apoptosis of HCC cells.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.