ObjectiveTo investigate the effects and underlying mechanisms of polydatin in delaying the progression of colitis-associated colorectal cancer （CAC） by constructing an azoxymethane （AOM）/dextran sulfate sodium （DSS）-induced CAC mouse model and conducting in vitro experiments. MethodsFifty-four male C57BL/6J mice were randomly divided into normal， model， and polydatin groups （0.045 g·kg^-1）. The CAC mouse model was established using AOM/DSS， and samples were collected at 4， 7， and 10 weeks. Body weight change rate， disease activity index （DAI）， and tumor formation were assessed. Hematoxylin-eosin （HE） staining was used to observe pathological injury in intestinal tissues. Immunohistochemistry （IHC） was performed to detect zonula occludens-1 （ZO-1） expression in colonic tissues， and Western blot was used to detect the expression of E-cadherin， N-cadherin， and Vimentin in colonic epithelial cells. Real-time PCR was used to measure mRNA expression of interleukin-17A （IL-17A）， Wnt3a， β-catenin， T cell factor 1 （Tcf1）， E-cadherin， N-cadherin， and Vimentin in colonic tissues. Flow cytometry was used to analyze the proportion of CD8⁺T cells and the expression of exhaustion-related molecules in tumors. Human colon cancer DLD-1 cells were cultured in a polydatin-containing medium， and wound healing assays were performed to observe migration changes. Real-time PCR was used to detect mRNA expression of interleukin-17 receptor A （IL-17RA）， Wnt3a， β-catenin， Tcf1， E-cadherin， N-cadherin， and Vimentin in DLD-1 cells. ResultsCompared with the normal group， the model group at all three time points showed significantly decreased body weight change rate （P<0.01）， significantly shortened colon length （P<0.01）， and markedly increased DAI scores （P<0.01）. HE staining revealed significant inflammatory cell infiltration in the submucosa of the colon in the model group， accompanied by epithelial dysplasia. ZO-1 expression in colonic tissues was significantly reduced （P<0.01）. The mRNA expression of the pro-inflammatory factor IL-17A and key molecules of the Wnt/β-catenin pathway （Wnt3a， β-catenin， Tcf1） was significantly elevated （P<0.05）. The mRNA and protein expression of epithelial-mesenchymal transition （EMT） markers N-cadherin and Vimentin was significantly upregulated （P<0.05）， while E-cadherin expression was significantly downregulated （P<0.05）. The proportion of tumor-infiltrating CD8⁺T cells expressing immunosuppressive molecules （TIM-3， LAG-3， PD-1） was significantly increased （P<0.05）. Compared with the model group， the polydatin group showed significant improvement in body weight and DAI score （P<0.01）， as well as recovery of colon length and tissue injury. ZO-1 expression in colonic tissue was significantly increased （P<0.01）， while IL-17A， Wnt3a， β-catenin， Tcf1， N-cadherin， and Vimentin expression levels were significantly decreased （P<0.05）， and E-cadherin expression was significantly increased （P<0.01）. Tumor-infiltrating CD8⁺ T cells expressing immunosuppressive molecules were significantly reduced （P<0.05）. In vitro experiments showed that polydatin significantly inhibited migration of DLD-1 cells （P<0.01） and reversed the upregulation of IL-17RA， Wnt3a， β-catenin， N-cadherin， and Vimentin mRNA， as well as the downregulation of E-cadherin mRNA （P<0.05）. ConclusionPolydatin inhibits IL-17A secretion and IL-17RA expression， improves the immune microenvironment， blocks activation of the Wnt/β-catenin signaling pathway， suppresses EMT markers （N-cadherin and Vimentin）， and restores tight junction protein expression in intestinal epithelial cells， thereby delaying the progression from colitis to colorectal cancer in mice.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To explore the clinical effect of cold treatment of replacement fluid in continuous blood purification(CBP)of patients with heat stroke.Methods Clinical data of 46 patients with heat stroke who were treated with CBP in Hainan Hospital of PLA General Hospital from July 2018 to September 2022 were retrospectively analyzed.The patients were assigned to control group(23 cases,conventional treatment for heat stroke and CBP with room temperature replacement fluid)and observation group(23 cases,conventional treatment for heat stroke and CBP with cooling replacement fluid).The body temperatures were compared between the two groups before treatment and 30 min,2 h,6 h,12 h and 24 h after treatment.The prothrombin activity(PTA),activated partial thromboplastin time(APTT),D-dimer(D-D),fibrinogen(FIB)and platelet count(PLT)before treatment and at 24 h(T1),3 d(T2)and 7 d(T3)after treatment,as well as the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score at 7 d after treatment were also compared between the two groups.Results There was no significant difference in temperature or coagulation function between the two groups before treatment(P>0.05).The temperature of the observation group was significantly different from that of the control group at 2 h,6h and 12h after treatment(P<0.05).After treatment,the levels of PTA,FIB and PLT in the observation group at T1,T2 and T3 were higher than those in the control group,while the level of D-D in the observation group was lower than that in the control group,and the APPT at T1 and T2 was significantly shorter than that in the control group(P<0.05).PTA,APPT,D-D,FIB and PLT of the two groups were improved after treatment(P<0.05).Conclusion The cold treatment of replacement fluid can quickly shorten the cooling time of patients with heat stroke during CBP,and significantly improve coagulation function.It is worthy of clinical promotion so as to improve the progrosis of patients with heat strok.

AIM: To investigate the risk factors of myopia, and provide evidence for the prevention and treatment of myopia in preschool children.METHODS:This is a retrospective case-control study. A total of 168 preschool-aged children(168 eyes)were enrolled from the ophthalmology department at Affiliated Hospital of Qingdao University between September 2021 and September 2023, selecting the eye with poorer vision for inclusion; the right eye was selected when both eyes had equal vision. Grouping criteria: Children with spherical equivalent(SE)>0 D and age-appropriate normal visual acuity(≥0.5 for ages 3-5; ≥0.7 for ages 6-7)were directly assigned to the non-myopia group. Children with SE <0 D underwent cycloplegic refraction after 3 days of 1% atropine sulfate gel application(three times daily). Those with SE ≤-0.50 D and failure to achieve age-normal visual acuity(<0.5 for ages 3-5; <0.7 for ages 6-7)were assigned to the myopia group, with 84 children(84 eyes)in each group. All participants underwent measurements of visual acuity, intraocular pressure, refraction, and ocular biometric parameters. Parents or guardians completed risk factor questionnaires during the visit, covering daily outdoor activity duration, daily electronic device usage/reading time, parental myopia status, maternal delivery mode, and full-term birth status.RESULTS:Significant differences were observed in uncorrected visual acuity, spherical power, SE, and axial length between the two groups of children(all P<0.05). No statistically significant differences were found in daily sleep duration, daily reading/homework time, maternal myopia status, mode of delivery, or full-term delivery status(all P>0.05). However, significant differences existed in daily outdoor activity time, daily electronic device usage duration, maternal myopia degree, paternal myopia degree, maternal age of myopia onset, and paternal age of myopia onset(all P<0.05). Logistic regression analysis identified the following risk factors for myopia in preschool children: daily outdoor activity under 2 h, daily electronic device use exceeding 60 min, maternal myopia degree, maternal early-onset myopia, paternal high myopia, and paternal early-onset myopia. Analysis of interaction effects children gender and myopia-related factors on SE revealed significant interactions of children gender with paternal myopia degree, maternal and paternal age of myopia onset(P<0.05). Simple effects analysis further demonstrated that girls exhibited higher degree of myopia than boys in families with paternal early-onset myopia, maternal early-onset myopia, or paternal high myopia(P<0.05).CONCLUSION:Insufficient daily outdoor activity time(under 1 h), daily electronic device use exceeding 60 min, and parental myopia are significant risk factors for myopia development in preschool children. Among these children, girls' refractive status was particularly associated with parental refractive status.

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.

Objective To investigate the early dynamic changes of biomarkers associated with capillary leak syndrome(CLS)in patients with severe acute pancreatitis(SAP)and their correlation with multiple organ failure(MOF).Methods A total of 171 SAP patients admitted to the West China Centre of Excellence for Pancreatitis,West China Hospital,Sichuan University between September 1,2019 and December 31,2020 were enrolled for this study.The patients were divided into MOF and non-MOF groups based on the occurrence of MOF in the first 5 days of hospitalization,and were further divided into subgroups based on the presence of moderate-to-severe intra-abdominal hypertension(IAH).We performed dynamic monitoring of the blood biomarkers(hematocrit[HCT].blood urea nitrogen[BUN].and creatinine[Cr]),plasma proteins(albumin[Alb].total protein[TP].and non-albumin plasma proteins[NAPP]),and intra-abdominal pressure.Trends in these indicators across groups were analyzed comprehensively.Results No significant differences in baseline data between the two groups were observed.The baseline data of the 2 groups were comparable.The MOF group had significantly higher rates of persistent systemic inflammatory response syndrome(SIRS)lasting 48 hours(91.3％vs.71.8％),ICU admission(70.4％vs.17.6％),and length-of-stay([32±17.7]days vs.[19.0±12.2]days)compared to those of the non-MOF group(P＜0.05).The incidences of respiratory,circulatory,and renal failures were higher in the MOF group than those in the non-MOF group,showing significant differences in circulatory failure(69％vs.3.5％)and renal failure(65.5％vs.3.5％)(P＜0.05).In the first 5 days of hospitalization,the MOF group showed significantly elevated BUN and Cr levels,while Alb and TP levels dropped rapidly upon admission and then gradually recovered.The NAPP level of the MOF group continued to decrease after admission,and on the third day after admission,the NAPP level was lower than that of the Non-MOF group,showing statistically significant difference(P＜0.001).The Alb/NAPP ratio of the MOF group decreased significantly on day 1 and then rapidly increased,showing significant differences between the groups on days 3 and 4(P=0.001).Subgroup analysis of MOF patients with moderate-to-severe IAH revealed similar trends in the dynamic changes and the overall changes in the indicators,and the difference was even more pronounced.The mixed linear model showed that the average levels of HCT,BUN,Alb/NAPP,and Alb/TP were higher and increased over time in the MOF combined with IAP subgroup(P＜0.001).Conclusion The CLS model of SAP patients is validated,confirming that CLS is a key factor in the progression from SIRS to MOF.The loss of NAPP is an early and important indicator of CLS persistence and progression to MOF.Additionally,moderate-to-severe IAH accelerates the deterioration of MOF.These findings provide valuable insights into the potential mechanisms of MOF and warrant further validation through large-scale prospective studies.

Objective To establish a method for simultaneous determination of trace levels of microcystins,cylindrospermopsin,anatoxin,and nodularin in lake water based on liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods After being adjusted to alkaline conditions and mixed with six internal standards,the water samples were enriched using dual HLB and ENVI-Carb cartridges.The eluates were then evaporated under nitrogen,reconstituted,and subjected to instrumental analysis.Both water and acetonitrile containing 0.1%formic acid were used as mobile phases.An ACQUITY UPLC? BEH C18 column(150 mm×2.1 mm,1.7 μm)was selected to separate the target cyanotoxins.Multiple reaction monitoring was applied for data acquisition,and quantification was accomplished using internal standard methods.Results Within certain concentration ranges,all 14 cyanotoxins examined in the study showed good linearity,with all correlation coefficients greater than 0.998.When the water volume was 100 mL,the limits of detection and quantification for the 14 cyanotoxins were 0.1-0.9 ng/L and 0.3-2.9 ng/L,respectively,and spiked recoveries and relative standard deviations were 81.7%-132.9%and 1.2%-14.9%,respectively.In the 10 lake water samples analyzed,cylindrospermopsin,anatoxin-α,and multiple microcystins were detected.Conclusion The method developed in the study has high-throughput capacity,as well as high sensitivity,accuracy,and reliability.The method can be applied in the simultaneous detection of microcystins,cylindrospermopsin,anatoxin,and nodularin in lake water.

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Objective To explore the changes in symptom clusters and core symptoms at different stages in col-orectal cancer patients undergoing postoperative chemotherapy,and to provide a reference for developing precise symptom management strategies in clinical practice.Methods 300 colorectal cancer patients who underwent post-operative chemotherapy at 2 tertiary hospitals in Tianjin from August 2023 to May 2024 were conveniently selected as the study subjects.General information questionnaires and the Chinese version of the MD Anderson Symptom In-ventory for Colorectal Cancer were used to survey patients during the first chemotherapy cycle(T1)and the third chemotherapy cycle(T2).Exploratory factor analysis was used to extract symptom clusters;R language was used to construct symptom networks.Results 300 questionnaires were distributed and collected at T1,and 264 question-naires were distributed and collected at T2,with a recovery rate of 88.00％.Colorectal cancer patients undergoing postoperative chemotherapy had 5 symptom clusters at T1,and 4 symptom clusters at T2.In the symptom network,distress was the symptom with the highest strength(rs=1.188),closeness centrality(rc=0.004),and betweenness centrality(rb=36)at T1.Distress was the symptom with the highest strength(rs=1.397),while decreased appetite had the highest closeness centrality(rc=0.004)and betweenness centrality(rb=39)at T2.Conclusion The symptom clusters in colorectal cancer patients undergoing postoperative chemotherapy remain stable over time.Distress is a stable core symptom during chemotherapy,while decreased appetite is a bridging symptom in the mid-chemotherapy phase.Healthcare providers should prioritize interventions for decreased appetite while addressing emotional symptoms to improve the efficiency of symptom management.