Ulcerative colitis （UC） is a chronic and relapsing inflammatory disease of the intestine. Intestinal fibrosis represents a severe co mplication and a potential risk factor for malignant transformation. Gentianopsis paludosa is one of the traditional Tibetan medicines commonly used for treating gastrointestinal disorders such as damp-heat diarrhea and dysentery. Its chemical composition is complex， encompassing xanthones， flavonoids， terpenoids， and other bioactive components， and it exhibits properties such as clearing heat， eliminating dampness， and detoxifying. This article reviews the research progress on the pharmacodynamic material basis and mechanisms of G. paludosa against UC and associated fibrosis. Findings suggest that its extracts （e.g.， aqueous extract， ethyl acetate extract） and active constituents （e.g.， 1-hydroxy-3，7，8-trimethoxyxanthone， ursolic acid， swertiamarin， luteolin） may inhibit inflammatory cytokines， combat oxidative stress， suppress cell apoptosis， regulate intestinal microbiota and their metabolites， protect the intestinal mucosal barrier， modulate immune responses， and inhibit epithelial-mesenchymal transition， through modulating relevant signaling pathways， such as nuclear factor-kappa B， B-cell lymphoma-2 （Bcl-2）/Bcl-2-associated X protein， and transforming growth factor-β 1 /Smad， thus exerting therapeutic effects against UC and its related fibrosis via these seven aspects.

Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective:To investigate the clinical efficacy and prognostic factors of neoadju-vant chemotherapy (NACT) and radical resection on adenocarcinoma of esophagogastric junction (AEG) and gastric adenocarcinoma (GC).Methods:The propensity score matching and retrospec-tive cohort study was conducted. The clinicopathological data of 263 patients with AEG and GC who were admitted to Peking University Cancer Hospital from March 2017 to March 2022 were collected. There were 204 males and 59 females, aged (60±10)years. Of the 263 patients, 81 cases with AEG were set as the AEG group, and 182 cases with GC were set as the GC group. Observation indicators: (1) propensity score matching and comparison of clinicopathological characteristics of patients between the two groups after matching; (2) evaluation of the efficacy of NACT and pathological conditions; (3) intraoperative and postoperative conditions; (4) follow-up; (5) analysis of factors affecting prognosis of patients. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney rank sum test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametric rank sum test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method with a caliper value of 0.02. Results:(1) Propensity score matching and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of 263 patients, 156 cases were succe-ssfully matched, including 78 cases in the AEG group and 78 cases in the GC group. After propensity score matching, the elimination of age and degree of tumor differentiation confounding bias ensured comparability between the two groups. (2) Evaluation of the efficacy of NACT and pathological condi-tions. After propensity score matching, cases with pathological complete response were 2 in the AEG group, versus 9 in the GC group, showing a significant difference between the two groups ( χ2=4.793, P<0.05). (3) Intraoperative and postoperative conditions. After propensity score matching, the operation time of AEG group was 225(200,283)minutes. The resection range (whole stomach, distal stomach, proximal stomach) were 68, 0, 10, respectively. The digestive tract reconstruction methods (Roux-en-Y, Billroth Ⅰ/Ⅱ/Uncut Roux-en-Y, esophageal residual gastric, double channel) were 68, 0, 5, 5, respectively. Duration of postoperative hospital stay was 12(10,16)days. Total hospi-talization expense was (114 400±4 828)yuan. The above indicators of the GC group were 200(174,234)minutes, 22, 55, 1, 21, 56, 0, 1, 10(9,11)days, (98 790±2 549)yuan, respectively. There were significant differences in the above indicators between the two groups ( Z=-3.813, χ2=85.875, 88.487, Z=-4.060, t=2.524, P<0.05). Cases of complication and cases of serious complication were 32 and 9 in the AEG group, versus 22 and 5 in the GC group, showing no significant difference between the two groups ( χ2=2.832, 1.256, P>0.05). (4) Follow-up. All 156 patients after propensity score matching were followed up after surgery, with a follow-up time of 51(range, 3-84)months. Number of death in the AEG group and GC group were 26 and 25 during the follow-up. The postoperative 3-, 5-year overall survival rate were 70.4%, 58.3% in patients of the AEG group, versus 75.7%, 62.6% in patients of the GC group, showing no significant difference in overall survival between the two groups ( χ2=0.141, P>0.05). (5) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that NACT, average tumor diameter after NACT, vascular tumor emboli were independent factors affecting prognosis of patients with AEG and GC after NACT and radical resection before propensity score matching ( hazard ratio=1.864, 1.807, 4.551, 95% confidence interval as 1.137-3.056, 1.124-2.903, 2.709-7.645, P<0.05). Conclusions:Compared with patients of GC, patients of AEG have a lower proportion of pathological complete response after NACT, but there is no signifi-cant difference in the incidence of complication and survival of patients with AEG and GC after NACT and radical resection. NACT, average tumor diameter after NACT, vascular tumor emboli are indepen-dent factors affecting prognosis of patients with AEG and GC after NACT and radical resection.

Objective:To explore the specificity of mediating effects of maladaptive cognition about self and maladaptive cognition about others in the context of childhood maltreatment and internalizing and externalizing problems in middle school students.Methods:A total of 788 middle school students from Hebei province were en-rolled in the study.The first data collection utilized the Childhood Trauma Questionnaire-Short Form(CTQ-SF)and the Posttraumatic Maladaptive Beliefs Scale(PMBS).After a 7-month interval,the second data collection was con-ducted with the Youth Self Report(YSR).The specificity of the mediating effects was examined by using Mplus 7.0 software.Results:Totally 72.3％of middle school students had experienced childhood abuse.Maladaptive cog-nition about self fully mediated the relationship between childhood maltreatment and adolescent internalizing prob-lems,with a mediation effect size of 0.22(95％CI:0.16-0.27).It partially mediated the relationship between childhood maltreatment and adolescent externalizing problems,with a mediation effect size of 0.13(95％CI:0.09-0.19).Maladaptive cognition about others only mediated the relationship between childhood maltreatment and adolescent externalizing problems,with a mediation effect size of-0.07(95％CI:-0.12--0.02),indicating a masking effect.Conclusion:Childhood maltreatment increases the likelihood of internalizing and externalizing prob-lems in middle school students.Childhood maltreatment increases internalizing and externalizing problems by in-creasing their maladaptive cognition of self,and childhood maltreatment increases their externalizing problems by increasing their maladaptive cognition of others.

Objective:To explore the specificity of mediating effects of maladaptive cognition about self and maladaptive cognition about others in the context of childhood maltreatment and internalizing and externalizing problems in middle school students.Methods:A total of 788 middle school students from Hebei province were en-rolled in the study.The first data collection utilized the Childhood Trauma Questionnaire-Short Form(CTQ-SF)and the Posttraumatic Maladaptive Beliefs Scale(PMBS).After a 7-month interval,the second data collection was con-ducted with the Youth Self Report(YSR).The specificity of the mediating effects was examined by using Mplus 7.0 software.Results:Totally 72.3％of middle school students had experienced childhood abuse.Maladaptive cog-nition about self fully mediated the relationship between childhood maltreatment and adolescent internalizing prob-lems,with a mediation effect size of 0.22(95％CI:0.16-0.27).It partially mediated the relationship between childhood maltreatment and adolescent externalizing problems,with a mediation effect size of 0.13(95％CI:0.09-0.19).Maladaptive cognition about others only mediated the relationship between childhood maltreatment and adolescent externalizing problems,with a mediation effect size of-0.07(95％CI:-0.12--0.02),indicating a masking effect.Conclusion:Childhood maltreatment increases the likelihood of internalizing and externalizing prob-lems in middle school students.Childhood maltreatment increases internalizing and externalizing problems by in-creasing their maladaptive cognition of self,and childhood maltreatment increases their externalizing problems by increasing their maladaptive cognition of others.

Mass spectrometry(MS)is one of the core technology in the field of clinical laboratory,which has a series of advantages include high sensitivity,high specificity,and the simultaneous analysis of multi-components.It shows great potential in metabolite detection,proteomic analysis,etc.,which can provide new pathways for early diagnosis and personalized treatment of complex diseases.In recent years,the research of MS technique appears rapid development trend in the field of clinical laboratory.This paper systematically combed the application status and research progress of MS techniques in clinical laboratory,which include mass spectrometry imaging(MSI),matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),inductively coupled plasma mass spectrometry(ICP-MS),cytometry by time-of-flight(CyTOF),and liquid chromatography-tandem mass spectrometry(LC-MS/MS).It focused on their practical applications in disease diagnosis,efficacy assessment,and prognosis judgment,and it anatomized the faced bottlenecks and problems of current technique.Based on the frontline technological trends,it explore the innovative directions of integrating MS technique with emerging bioinformatics,microfluidics,etc.,so as to provide theoretical basis and practical reference for promoting the standardized and intelligent development of MS technique in clinical laboratory,and help its wide application in clinical diagnosis and treatment.

Mass spectrometry(MS)is one of the core technology in the field of clinical laboratory,which has a series of advantages include high sensitivity,high specificity,and the simultaneous analysis of multi-components.It shows great potential in metabolite detection,proteomic analysis,etc.,which can provide new pathways for early diagnosis and personalized treatment of complex diseases.In recent years,the research of MS technique appears rapid development trend in the field of clinical laboratory.This paper systematically combed the application status and research progress of MS techniques in clinical laboratory,which include mass spectrometry imaging(MSI),matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),inductively coupled plasma mass spectrometry(ICP-MS),cytometry by time-of-flight(CyTOF),and liquid chromatography-tandem mass spectrometry(LC-MS/MS).It focused on their practical applications in disease diagnosis,efficacy assessment,and prognosis judgment,and it anatomized the faced bottlenecks and problems of current technique.Based on the frontline technological trends,it explore the innovative directions of integrating MS technique with emerging bioinformatics,microfluidics,etc.,so as to provide theoretical basis and practical reference for promoting the standardized and intelligent development of MS technique in clinical laboratory,and help its wide application in clinical diagnosis and treatment.

Objective:To investigate the clinical efficacy and prognostic factors of neoadju-vant chemotherapy (NACT) and radical resection on adenocarcinoma of esophagogastric junction (AEG) and gastric adenocarcinoma (GC).Methods:The propensity score matching and retrospec-tive cohort study was conducted. The clinicopathological data of 263 patients with AEG and GC who were admitted to Peking University Cancer Hospital from March 2017 to March 2022 were collected. There were 204 males and 59 females, aged (60±10)years. Of the 263 patients, 81 cases with AEG were set as the AEG group, and 182 cases with GC were set as the GC group. Observation indicators: (1) propensity score matching and comparison of clinicopathological characteristics of patients between the two groups after matching; (2) evaluation of the efficacy of NACT and pathological conditions; (3) intraoperative and postoperative conditions; (4) follow-up; (5) analysis of factors affecting prognosis of patients. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney rank sum test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametric rank sum test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method with a caliper value of 0.02. Results:(1) Propensity score matching and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of 263 patients, 156 cases were succe-ssfully matched, including 78 cases in the AEG group and 78 cases in the GC group. After propensity score matching, the elimination of age and degree of tumor differentiation confounding bias ensured comparability between the two groups. (2) Evaluation of the efficacy of NACT and pathological condi-tions. After propensity score matching, cases with pathological complete response were 2 in the AEG group, versus 9 in the GC group, showing a significant difference between the two groups ( χ2=4.793, P<0.05). (3) Intraoperative and postoperative conditions. After propensity score matching, the operation time of AEG group was 225(200,283)minutes. The resection range (whole stomach, distal stomach, proximal stomach) were 68, 0, 10, respectively. The digestive tract reconstruction methods (Roux-en-Y, Billroth Ⅰ/Ⅱ/Uncut Roux-en-Y, esophageal residual gastric, double channel) were 68, 0, 5, 5, respectively. Duration of postoperative hospital stay was 12(10,16)days. Total hospi-talization expense was (114 400±4 828)yuan. The above indicators of the GC group were 200(174,234)minutes, 22, 55, 1, 21, 56, 0, 1, 10(9,11)days, (98 790±2 549)yuan, respectively. There were significant differences in the above indicators between the two groups ( Z=-3.813, χ2=85.875, 88.487, Z=-4.060, t=2.524, P<0.05). Cases of complication and cases of serious complication were 32 and 9 in the AEG group, versus 22 and 5 in the GC group, showing no significant difference between the two groups ( χ2=2.832, 1.256, P>0.05). (4) Follow-up. All 156 patients after propensity score matching were followed up after surgery, with a follow-up time of 51(range, 3-84)months. Number of death in the AEG group and GC group were 26 and 25 during the follow-up. The postoperative 3-, 5-year overall survival rate were 70.4%, 58.3% in patients of the AEG group, versus 75.7%, 62.6% in patients of the GC group, showing no significant difference in overall survival between the two groups ( χ2=0.141, P>0.05). (5) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that NACT, average tumor diameter after NACT, vascular tumor emboli were independent factors affecting prognosis of patients with AEG and GC after NACT and radical resection before propensity score matching ( hazard ratio=1.864, 1.807, 4.551, 95% confidence interval as 1.137-3.056, 1.124-2.903, 2.709-7.645, P<0.05). Conclusions:Compared with patients of GC, patients of AEG have a lower proportion of pathological complete response after NACT, but there is no signifi-cant difference in the incidence of complication and survival of patients with AEG and GC after NACT and radical resection. NACT, average tumor diameter after NACT, vascular tumor emboli are indepen-dent factors affecting prognosis of patients with AEG and GC after NACT and radical resection.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.