A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveTo investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. MethodsA total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ²=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ²=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ²=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ²=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. ConclusionACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

Objective:To explore the predictive value of Nomogram prediction model for poor prognosis of severe pneumonia(SP)based on micrornas(miR)-221-3p,miR-155-5p and confusion,uremia,respiratory,BP,age 65years(CURB-65)score.Methods:439 SP patients who were admitted to Yichun People's Hospital from January 2021 to June 2024 were prospectively selected,they were randomly divided into modeling group(n=307)and validation group(n=132)according to the ratio of 7:3.The serum levels of miR-221-3p and miR-155-5p were detected before treatment,and the CURB-65 score was used for evaluation.The prognosis of SP patients within 28 days of hospitalization was observed,and the SP patients were divided into death group and survival group according to the prognosis within 28 days.Lasso regression was used to analyze the influencing factors of poor prognosis of SP patients,and multivariate Logistic regression was used to analyze the risk factors for poor prognosis of SP patients.A Nomogram prediction model for poor prognosis of SP patients was constructed,and the receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the Nomogram model for poor prognosis of SP patients.Results:The mortality rates in the modeling group and the validation group were 29.32％(90/307)and 28.79％(38/132)respectively,and there was no significant difference in mortality rates and clinical data between the two groups(P＞0.05).The age,proportion of underlying lung disease,pneumonia severity index(PSI)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,CURB-65 score,serum miR-221-3p,miR-155-5p,C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and procalcitonin(PCT)indexes in modeling and validation of the death group were higher than those of survival group(P＜0.05).Logistic multivariate regression analysis showed that advanced age,high APACHE Ⅱ score,high expression of miR-221-3p,high expression of miR-155-5p and high CURB-65 score were risk factors for poor prognosis of SP(P＜0.05).The area under the curve(AUC)of the constructed Nomogram prediction model for the poor prognosis of SP was 0.824,which had good prediction efficiency.Conclusion:High expression of miR-221-3p,high expression of miR-155-5p,high CURB-65 score,older age and high APACHE Ⅱ score are risk factors for poor prognosis of SP patients,and the Nomogram prediction model based on the above factors has a high predictive value for the poor prognosis of SP.

Objective:In order to clarify the ABO phenotype and genotype,and explore the molecular biological mechanism,serological detection,genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.Methods:ABO forward and reverse blood typing,H antigen identification,capillary centrifugation test and salivary substance detection were performed by classical serological method,moreover,polymerase chain reaction-sequence specific primer(PCR-SSP)was used for ABO genotyping,ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.Results:Mixed field agglutination with anti-A,anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests,agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests.3+agglutination strength was showed with anti-H.In capillary centrifugation experiment,erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A.Substances A and H were detected in saliva.The patient was assigned an A3 phenotype according to serological characteristics.Sequencing results of ABO gene 1-7 exons showed c.261delG,c.467C＞T,c.865A＞G,in which,865A＞G was the first discovered mutation,and this new mutation had been submitted to GenBank with accession number PP187306.Conclusion:A novel site mutation c.865A＞G is reported in this study,and this new mutation can result in a replacement of Met with Val at residue 289(p.Met289Val)and lead to an A3 phenotype.

Objective To investigate the clinical efficacy and safety of wentong guasha combined with herbal enema in the treatment of acute attack of chronic pelvic inflammatory disease.Methods From January 2023 to December 2024,patients with acute attack of chronic pelvic inflammatory disease diagnosed and treated at Foshan Women and Children Hospital Affiliated to Guangdong Medical University were selected and randomly divided into an experimental group and a control group.The control group received herbal enema therapy,while the experimental group received additional wentong guasha therapy on the basis of the control group's treatment.Both groups were treated for two weeks.The clinical efficacy,safety outcomes,as well as Visual Analog Scale(VAS)scores for pain and Pittsburgh Sleep Quality Index(PSQI)scores before treatment and after the 3rd and 7th days of treatment were compared between the two groups.Results A total of 120 patients were included,with 60 cases in each group.After treatment,the total effective rate was 90.00%in the experimental group and 76.67%in the control group,showing a statistically significant difference between the two groups(P<0.05).On the 3rd day of treatment,the VAS score of the experimental group was significantly lower than that of the control group(P<0.05).By the 7th day of treatment,both the VAS and PSQI scores of the experimental group were significantly lower than those of the control group(P<0.05).No adverse reactions were observed in either group.Conclusion Compared with herbal enema therapy,wentong guasha combined with herbal enema demonstrated more significant clinical efficacy in patients with acute attack of chronic pelvic inflammatory disease,markedly reduced pain scores,improved sleep quality,and showed good safety,indicating its potential value for clinical promotion and application.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective To investigate the effect and mechanism of Taxilli Herba decoction in preventing miscarriage in rats with threatened abortion.Methods Seventy-two SPF-grade SD rats were co-housed at a male-to-female ratio of 2∶1.Forty-eight pregnant rats were subsequently divided into a normal group,a threatened abortion model group,a positive control group,as well as Taxilli Herba decoction low/medium/high dose groups(n=8 rats per group).Rats in the positive control group received 3.02 mg/kg dydrogesterone intragastrically,and rats in the low-,medium-,and high-dose Taxilli Herba decoction groups received 2.5,5,and 10 g/kg Taxilli Herba decoction intragastrically,respectively.The normal and model groups received intragastric distilled water once a day for 10 consecutive days.On day 10 after administration of the corresponding treatment,rats in all groups except the normal group received intragastric administration of 3.75 mg/kg mifepristone suspension.The effects of Taxilli Herba on the vaginal bleeding rate and abortion rate were observed.Serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E),progesterone(P),vascular endothelial growth factor(VEGF),testosterone(T),and aromatase and E and P levels in the ovary in pregnant rats were detected by enzyme-linked immunosorbent assay.Expression levels of E receptor(ER),P receptor(PR),VEGF receptor 2(VEGFR2),and platelet endothelial cell adhesion molecule-1(CD31)in the uterine decidua in pregnant rats were detected by immunofluorescence staining,and semi-quantitative analysis was performed.Results Mifepristone significantly increased the vaginal bleeding rate and abortion rate in pregnant rats,but these were effectively reduced by treatment with Taxilli Herba water decoction.Taxilli Herba water decoction also increased serum E,P,and VEGF,and ovary levels of E and P(P＜0.05).The treatment also decreased serum LH,maintained the secretion of FSH,and enhanced ER,PR,VEGFR2,and CD31 expression in decidual tissue.Conclusions Taxilli Herba demonstrated effective miscarriage-prevention effects in a rat model of threatened abortion.Its mechanism of action involves regulating the normal physiological function of the hypothalamic-pituitary-gonadal axis upstream of the uterus,and enhancing the expression of the downstream P/PR/VEGF/VEGFR2 and E/ER/VEGF/VEGFR2 pathways.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.