ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg^-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C⁺ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L^-1 on LPS-induced differentiation of RAW264.7 cells into Ly6C^hi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6C^hi and Ly6C^lo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6C^hi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6C^hi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6C^hi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6C^hi monocytes/macrophages.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

ObjectiveTo explore the evolution of medication patterns and syndrome-herb associations of traditional Chinese medicine （TCM） in treating inflammatory bowel disease （IBD）， providing a theoretical foundation for precise syndrome differentiation and treatment in clinical practice. MethodsMedical case literature on TCM treatment of IBD from 1960 to 2024 was retrieved to establish a database. Frequency statistics， cluster analysis， change point detection， and association rule mining were employed to comprehensively analyze the syndrome distribution， therapeutic methods， medication patterns， and their temporal variations. ResultsA total of 685 medical cases were included. Common syndromes were dampness-heat （66.42%） and spleen deficiency （56.20%）. Primary therapeutic methods included heat clearing （63.65%）， spleen invigorating （47.45%）， and dampness draining （36.79%）. High-frequency herbs included Coptidis Rhizoma （354）， Paeoniae Radix Alba （303）， Aucklandiae Radix （292）， Codonopsis Radix （253）， and Glycyrrhizae Radix et Rhizoma （244）. Initial prescription clustering revealed three core therapeutic method combinations： heat clearing and detoxifying （represented by Baitouweng Tang）， spleen invigorating and Qi reinforcing （represented by Shenling Baizhusan）， and cold-heat regulation （represented by Wumeiwan combined with Shaoyao tang）. Temporal analysis identified 2008 as a key transition point in TCM treatment of IBD， with significantly increased usage frequency of heat-clearing and dampness-drying herbs such as Fraxini Cortex， Phellodendri Chinensis Cortex， Sophorae Flavescentis Radix， and Scutellariae Radix as well as hemostatic herbs such as carbonized Sanguisorbae Radix， Bletillae Rhizoma， Agrimoniae Herba， and Notoginseng Radix et Rhizoma. Follow-up efficacy analysis showed median improvement rates of 64.0% at the first follow-up， 76.0% at the second follow-up， and 78.7% at the third follow-up. Syndrome-drug association analysis revealed specific herb pairs with significant therapeutic advantages， including Notoginseng Radix et Rhizoma + Coicis Semen， Sanguisorbae Radix + Coptidis Rhizoma， and Codonopsis Radix + Aconii Lateralis Radix Praeparaia. ConclusionTCM medication patterns for treating IBD demonstrate distinct temporal evolution characteristics， with significantly increased usage frequency of herbs such as Fraxini Cortex， Notoginseng Radix et Rhizoma， and Agrimoniae Herba. Significant therapeutic method-herb associations and syndrome-herb association patterns exist， with the formation of specific herb pairs， providing evidence-based support for precise syndrome differentiation and treatment of IBD.

Objective To investigate the relationship between mean platelet volume/lymphocyte ratio(MPVLR)and left atrial thrombosis in elderly patients with non-valvular atrial fibrillation(NVAF).Methods A total of 178 elderly patients with NVAF admitted to the hospital from January 2019 to December 2022 were enrolled in the study.The patients were divided into thrombosis group(28 cases)and non-throm-bosis group(150 cases)according to the left atrial thrombosis judged by using esophageal echocardiography(TEE).The white blood cell count(WBC),red blood cell count(RBC),lymphocyte count,lymphocyte pro-portion,platelet count(PLT)and mean platelet volume(MPV)were detected by automatic blood cell analy-zer,and MPVLR was calculated.The liver and kidney function indicators and blood lipid indicators were detec-ted by automatic biochemical analyzer.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV,lymphocyte ratio and MPVLR for left atrial thrombosis in NVAF patients.Multiva-riate Logistic regression was used to analyze the influencing factors of left atrial thrombosis in elderly NVAF patients.Results MPV,lymphocyte proportion and MPVLR in the thrombosis group were higher than those in the non-thrombosis group,and the differences were statistically significant(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of MPV,lymphocyte ratio and MPVLR for predicting left atrial thrombosis in NVAF patients were 0.821(95％CI:0.764-0.882),0.771(95％CI:0.714-0.842)and 0.901(95％CI:0.861-0.949).respectively.The course of disease in the thrombosis group was longer than that in the non-thrombosis group,the proportion of patients with chronic heart failure,the proportion of patients with stroke,CH A2DS2-VASc score,LAEF,LAD,LVEDV,MPVLR,serum uric acid,MPV,lymphocyte proportion and MPVLR were higher than those in the non-thrombosis group,and LVEF was lower than that in the non-thrombosis group,the differences were statistically significant(P＜0.05).Multivariate Logistic regression a-nalysis showed that disease duration ≥1.93 years(OR=3.050,95％CI:1.928-4.824),chronic heart failure(OR=3.333,95％CI:1.808-6.144),MPVLR≥3.10(OR=3.873,95％CI:1.734-8.650)were independ-ent risk factors for left atrial thrombosis in elderly NVAF patients(P＜0.05).Conclusion The increase of MPVLR is associated with left atrial thrombosis in elderly patients with NVAF,and it can be used as a an in-dicator to predict left atrial thrombosis in patients with NVAF.

Objective:To investigate the necessity of adaptive re-planning during radiotherapy for nasopharyngeal carcinoma (NPC) and its impact on dose improvement.Methods:Clinical data of 89 NPC patients admitted to Sun Yat-sen University Cancer Center from July 2014 to December 2017 were retrospectively analyzed. All patients received 25+7 rounds of adaptive re-planning during radiotherapy. Plan-A was defined as the initial CT scan-based 25-fraction radiotherapy plan, while plan-B was defined as the re-planned 7-fraction radiotherapy plan based on a subsequent CT scan. The changes in the target and parotid gland volumes were compared between plan-A and plan-B. Plan-I was a one-time simulation of plan-A extended to 32 fraction radiotherapy plan, and plan-II was generated through registration and fusion of the plan-A and plan-B for adaptive re-planning. The differences in dose metrics, homogeneity index (HI), conformity index (CI), and dose to organs at risk (OAR) were compared between plan-I and plan-II. Statistical analysis was performed by using paired t-test. Results:Compared with plan-A, the gross tumor volume of massive bleeding lesions (GTV nx) and parotid gland volume of plan-B were decreased by 13.14% and 11.12%, respectively (both P<0.001). While planning clinical target volume of metastatic lymph nodes (PCTV nd) of plan-B was increased by 7.75%( P<0.001). There were significant changes in the lymph nodes of plan-A and plan-B. The D mean, D 5%, D 95% of massive bleeding lesions planning target volume (PTV nx) and D 5% of high risk planning target volume (PTV1) in plan-II were all significantly higher than those in plan-I (all P<0.05). The CI of PTV nx and PTV1 in plan-II was closer to 1 than that in plan-I. In all assessed OAR, the D mean, D 50%, and D max of plan-II were significantly lower than those of plan-I (all P<0.05). Conclusions:During radiotherapy, NPC patients may experience varying degrees of primary tumor shrinkage, parotid gland atrophy, and lymph node changes. It is necessary to deliver re-planning and significantly improve the dose of target areas and OAR.

Autophagy is mediated by multiple molecules and pathways. In cardiovascular diseases， autophagy can play a role through key signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）/mTOR， mitogen-activated protein kinases （MAPK）， p53， Wnt/β-catenin， etc. Traditional Chinese medicine （TCM） monomers for promoting blood circulation and removing blood stasis such as hydroxysafflor yellow A， ginsenoside Rb1， salidroside， ligustrin， curcumin， etc.， and TCM prescription and preparations such as Huangqi baoxin decoction， Taohong siwu decoction， Tongxinluo capsule， Shuangshen ningxin capsule， Suxiao jiuxin pills， etc. can regulate autophagy through the above-mentioned key signaling pathways， thereby alleviating the progression of cardiovascular diseases.

Objective Evaluate the performance of the encephalon state index(ESI)in depth of anesthesia monitoring during clinical surgery,compared with the bispectral index(BIS).Methods ESI and BIS data were collected from 60 patients in a single-center clinical trial to compare their efficacy in measuring the depth of anesthesia.Results Consistency analysis revealed mean differences and standard deviations of-0.18±5.42 and-0.11±6.51 between ESI and BIS for awake and anesthetized states,respectively.Correlation analysis showed a correlation coefficient of 0.92 throughout the operative period.Prediction probability analysis indicated that both ESI and BIS had prediction probabilities of 0.97,effectively predicting anesthesia status.Conclusion ESI and BIS show good equivalence in monitoring depth of anesthesia during clinical surgery,which meet the requirements of clinical anesthesia.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.