Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Objective To investigate the characteristics of human papillomavirus (HPV) prevalence and genotype distribution of 18 535 cases in Yuncheng . Methods A sample of 18535 residents who underwent HPV testing in our hospital from August 2020 to September 2023 were enrolled, and HPV genotyping was done to all samples. Then the rate of HPV infection, age distribution, genotype distribution, and multiple infections were statistically analyzed. Results Of the 18,535 subjects included, a total of 4,639 tested positive for HPV, demonstrating a positive rate of 25.03%. The positive rate of HPV infection varied among different age groups (χ²=29.587, P<0.05), with higher rates found in <25 years old group (29.61%) and >60 years old group (25.89%). Overall, 23 genotypes, covering 5315 viruses, were detected. There were 5 low-risk genotypes with the highest percentage of HPV42 (9.29%), and there were 18 high-risk genotypes with HPV52, HPV58, HPV66 and HPV53, subtypes as the most frequent subtypes, accounting for 13.64%, 8.97%, 7.41% and 7.04%, respectively. The type of HPV infection was predominantly single infections, with an overall single infection rate of 21.62% (4008/18535), which accounted for 86.40% (4 008/4 639) of all positive cases, and a multiple genotype infections rate of 3.40% (631/18535). The 25-34 year old group accounted for the largest proportion of single infections (25.12%), while the <25 year old group accounted for the largest proportion of multiple genotype infections (30.74%). Conclusion The prevalence rate of HPV infection in Yuncheng is 25.03%, with a higher positive rate in the <25 years age group and the >60 years age group. A total of 23 HPV genotypes are detected, of which the main genotypes are HPV42, HPV58, HPV66 and HPV53, and the type of infection is dominated by single infections.

Objective To investigate the role of Toll-like receptor 4(TLR4)in hepatocyte regeneration after acet-aminophen(APAP)-induced injury in human normal liver cell(L02)and its possible mechanism.Methods L02 cells were cultured in vitro,and cell viability was detected by CCK-8 assay.The optimal concentration and duration of APAP and the concentration of TLR4 inhibitor(TAK-242)were determined.The protein expression levels of nu-clear factor-κB(NF-κB),microtubule-associated protein light chain 3(LC3),p62,receptor interacting protein kinase 1(RIP1),receptor interacting protein kinase 3(RIP3),signal transducer and activator of transcription 3(STAT3),phosphorylation of STAT3(p-STAT3),proliferating cell nuclear antigen(PCNA)and Cyclin D1 were detected by Western blot.The mRNA expression levels of TLR4,NF-κB,tumor necrosis factor-α(TNF-α),inter-leukin-6(IL-6),interleukin-1 β(IL-1 β),PCNA,Cyclin D1 and Ki67 were detected by qRT-PCR.Results Ac-cording to the results of CCK-8,L02 cells were treated with 5 mmol/L APAP for 24,36,48 h to simulate liver in-jury and regeneration model in vitro,and TAK-242 100 nmol/L was pretreated 2 ht before APAP to inhibit TLR4.Compared with the control group,the protein levels of NF-κB,RIP1,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TNF-α,IL-1 β and PCNA increased in the APAP 24 h group;the protein levels of NF-κB,RIP1,RIP3,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1 β,PCNA and Cyclin D1 in-creased in the APAP 36 h group;the protein levels of NF-κB,RIP1,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA,Cyclin D1 and Ki67 increased in the APAP 48 h group.The protein levels of NF-κB,RIP1,RIP3,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA,Cyclin D1,Ki67 significantly decreased in APAP+TAK-242 24 h and 48 h group than the APAP group at the same time point;the protein levels of NF-κB,PCNA and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA and Ki67 in APAP+TAK-242 36 h group were also significantly lower than those in APAP 36 h group.Compared with the control group,autophagy was activated in the APAP group,while autophagy was inhibited in the APAP+TAK-242 group.Conclusion TLR4 may affect the TLR4/NF-κB pathway,up-regulate the levels of inflammatory factors and autophagy,and promote hepatocyte regeneration after APAP-in-duced liver injury in L02 cells.

Objective:To explore the effect of humanistic care combined with Morita therapy on anxiety state of hemodialysis patients.Methods:A self-controlled study was conducted on 54 patients with end-stage renal disease and anxiety who received maintenance hemodialysis in China-Japan Friendship Hospital from August 2020 to August 2022. All patients were treated with humanistic care nursing and Morita therapy for one month. The Self Rating Anxiety Scale (SAS) scores of the patients before and after the intervention were compaired. The comparison of quantitative data was conducted by paired t-test, and the comparison of qualitative data was conducted by χ2 test. The correlation between different factors and anxiety was analyzed by Spearman correlation analysis. Results:Among the 54 patients, there were 26 males and 28 females, aged (61.8±16.3) years (ranging from 29 to 88 years). The SAS score after the intervention (44.0±11.1) was lower than that before the intervention (51.9±8.5) ( t=5.395, P<0.001). The anxiety of patients was related to their age ( r=0.305), employment status ( r=0.270) and marital status ( r=0.397) (all P<0.05). The satisfaction of patients with care measures and nursing before and after the intervention was 45.6% and 87.7%, respectively ( χ2=5.720, P<0.05). Conclusion:After receiving combined humanistic care nursing and Morita therapy, patients in a state of anxiety could experience significant psychological improvement, which is conducive to the successful completion of hemodialysis treatment and enhances the quality of life for patients.

Objective:To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms.Methods:A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1β and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1β and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ (LC3-Ⅱ/Ⅰ) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy.Results:Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1β and IL-6 in serum and BALF were significantly increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1β and IL-6 in both serum and BALF were significantly decreased [IL-1β (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 protein expression were significantly increased [LC3-Ⅱ/Ⅰ ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. Conclusion:The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.

Objective:To explore the cortical abnormalities in brain regions in adolescent with self-injury and the correlation between cortical structural changes and clinical emotional manifestations.Methods:From April 2023 to June 2024, totally 38 adolescents with self-injury(self-injury group) from psychological outpatient department of First People’s Hospital of Changzhou and 41 healthy volunteers (HC group) matched with age, gender and years of education were selected.T1-weighted magnetic resonance imaging and clinical data of all participants were collected. All of them were investigated by the 17-item Hamilton depression scale (HAMD-17) and Hamilton anxiety scale (HAMA). Image preprocessing and surface-based morphometry analysis were performed by the DPABISurf software. Cortical parameters from regions showing significant differences were extracted, which were then evaluated the correlation with the emotional scores based on Spearman correlation analysis by SPSS 29.0 software.Results:Compared with HC group, self-injury group showed reduced thickness in areas primarily involving the left somatosensory and motor cortex, left paracentral lobular and mid cingulate cortex, left posterior cingulate cortex and premotor cortex(MNI: cluster 1: x=-17.73, y=-32.81, z=43.87, cluster 2: x=-35.97, y=-8.72, z=52.01, cluster 3: x=-18.94, y=-41.39, z=65.94)(all P<0.05). Lower sulcal depth in the left orbital and polar frontal cortex (MNI: x=-39.9, y=47.92, z=-5.42) ( P<0.05) and higher mean curvature in the right superior parietal cortex (MNI: x=21.89, y=-61.89, z=50.55) ( P<0.05) were found in the self-injury group. In the self-injury group, Spearman correlation analysis revealed negative correlations between cortical thickness in the regions of interest and clinical emotional scores (HAMD-17: r=-0.385, -0.332, P<0.05; HAMA: r=-0.395, -0.481, P<0.05), primarily involving the left supplementary motor area, left premotor cortex and the left somatosensory and motor cortex. Conclusion:The perception and execution cortex of adolescents with self-injury shows surface morphological abnormalities, which may be relevant to clinical emotional manifestations.

Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.