OBJECTIVE To analyze the safety and efficacy of vonoprazan （VPZ） in the treatment of peptic ulcer （PU） and post-endoscopic submucosal dissection （ESD） ulcers， providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI， Wanfang， VIP， CBM， PubMed， Embase， Web of Science， and the Cochrane Library， meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening， data extraction， quality assessment of included studies， and evaluation of literature overlap. By employing the umbrella review analysis， a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included， with quality ranging from high to very low； all outcome measures involved showed a very high level of overlap in the included meta-analyses （corrected covered area： 22.22%-100%）. In the treatment of post-ESD ulcers， compared to proton pump inhibitor （PPI）， VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR＝1.27， 95%CI （1.03， 1.56）， Z＝2.21， P＝ 0.027] and the ulcer contraction rate post-ESD [MD＝0.08， 95%CI （0.00， 0.16）， Z＝2.09， P＝0.037]， while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR＝0.49， 95%CI （0.32， 0.73）， Z＝3.49， P＝0.001]； the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR＝0.47， 95%CI （0.25， 0.90）， Z＝2.28， P＝0.02]. In the treatment of PU， the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR＝1.13， 95%CI （1.02， 1.26）， Z＝2.38， P＝0.017]. CONCLUSIONS For post-ESD ulcers， VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However， it does not offer advantages in terms of safety for duodenal ulcer treatment.

Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

ObjectiveTo establish a mouse model of particulate matter 2.5 （PM_2.5）-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM_2.5-induced ocular surface damage by regulating the reactive oxygen species （ROS）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop （0.1 mL） of 5 g·L^-1 PM_2.5 suspension in both eyes， four times daily. Successfully modeled mice were randomized into four groups （n=10）： Model， p38 MAPK inhibitor， Chufeng Yisuntang， and combination （Chufeng Yisuntang at 7.3 g·kg^-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg^-1）. Chufeng Yisuntang was administered via gavage， and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion， tear film break-up time， and corneal fluorescein staining were assessed. After intervention for 4 weeks， hematoxylin and eosin （HE） staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum levels of ROS， malondialdehyde （MDA）， superoxide dismutase （SOD） 1， and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels， respectively， of p38 MAPK， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3） in the corneal tissue. ResultsCompared with the control group， the model group exhibited reduced tear secretion volume and tear film breakup time， along with increased corneal fluorescein staining scores （P<0.01）. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group demonstrated increased tear secretion volume and tear film breakup time， along with decreased corneal fluorescein staining scores （P<0.01）. HE staining revealed that compared with the control group， the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness， along with reduced meibomian gland acini and intensely stained， densely packed nuclei around the acini. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group showed intact corneal structure， improved cell morphology， and reduced damage severity. ELISA revealed elevated ROS and MDA levels （P<0.01） and decreased SOD1 and SOD2 levels （P<0.01） in the model group compared with the control group. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination lowered ROS and MDA levels （P<0.01）， while raising SOD1 and SOD2 levels （P<0.05， P<0.01）. Western blot revealed that compared with the control group， the model group exhibited increased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and reduced protein level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the protein level of Bcl-2 （P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and increased protein level of Bcl-2 （P<0.01）. Real-time PCR revealed that compared with the control group， the model group exhibited upregulated mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， and downregulated mRNA level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the mRNA level of Bcl-2 （P<0.05， P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased mRNA levels of p38 MAPK， Bax， and Caspase-3 expression （P<0.05， P<0.01） and increased mRNA level of Bcl-2 （P<0.01）. ConclusionChufeng Yisuntang may partially protect against PM_2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway， enhancing antioxidant defense， and reducing epithelial apoptosis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

Medical artificial intelligence （AI） is a new type of application formed by the combination of machine learning， computer vision， natural language processing， and other technologies with clinical medical treatment. With the continuous iteration and development of relevant technologies， medical AI has shown great potential in improving the efficiency of diagnosis and treatment， and service quality， but it also increases the possibility of triggering ethical issues. Ethical issues resulting from the clinical application of medical AI were analyzed， including the lack of algorithmic interpretability and transparency of medical AI， leading to information asymmetry and cognitive discrepancies； the concerning status of security and privacy protection of medical data； and the complex and unclear division of responsibilities due to the collaborative participation of multiple subjects in the clinical application of medical AI， resulting in increased difficulty in the identification of medical accidents and clarification of responsibilities. The paper proposed the principles of not harming patients’ interests， physician’s subjectivity， fairness and inclusiveness， and rapid response. It also explored the strategies and implementation paths for responding to the ethical issues of medical AI from multiple perspectives， including standardizing the environment and processes， clarifying responsibility attribution， continuously assessing the impact of data protection， guaranteeing data security， ensuring model transparency and interpretability， carrying out multi-subject collaboration， as well as the principles of being driven by ethical values and adhering to the “human health-centeredness.” It aimed to provide guidance for the healthy development of medical AI， ensuring technological progress while effectively managing and mitigating accompanying ethical risks， thereby promoting the benign development of medical AI technology and better serving the healthcare industry and patients.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.