Inflammatory Bowel Diseases(IBD)is a class of genetically related diseases caused by multiple genes and environmental factors that accelerate the disturbance of the immune-gut-microbiome axis.Lesions often involve multiple organs and systems.Biological agents are an important means of treating IBD and its extraintestinal manifestations.Current studies suggest that biologics can bring benefits to patients,but paradoxical skin lesions,joint lesions,and ocular lesions appear during the treatment.Diseases,pulmonary lesions and other manifestations or lesions are easily ignored in clinical practice,thereby delaying the patient's condition and affecting the patient's quality of life.Therefore,by summarizing the clinical characteristics and diagnosis and treatment experience of contradictory extraintestinal manifestations in the current application of biological agents,this review aims to improve the understanding of clinicians,identify this clinical manifestation early,and avoid delaying the patient's condition.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To investigate the influencing factors for chronic pancreatitis(CP)complicated by pancreatogenic portal hypertension(PPH),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University,Chuxiong Yi Autonomous Prefecture People's Hospital,Wenshan People's Hospital,and Puer People's Hospital from January 2017 to December 2022,and these patients were enrolled as PPH group.The incidence density sampling method was used to select 198 CP patients from databases as control group.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The Least Absolute Shrinkage and Selection Operator(LASSO)regression model was used to identify the potential predictive factors for CP complicated by PPH,and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors,which were used to establish a nomogram prediction model.The receiver operating characteristic(ROC)curve,the calibration curve,and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model,and the clinical decision curve was used to assess the clinical practicability of the model.Results There were significant differences between the two groups in sex,history of recurrent acute pancreatitis attacks,acute exacerbation of CP,bile duct stones,peripancreatic fluid accumulation,pseudocysts,pulmonary infection,elevated C-reactive protein(CRP),elevated procalcitonin,fibrinogen(FIB),neutrophil-lymphocyte ratio(NLR),gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,low-density lipoprotein(LDL),serum amylase,D-dimer,and serum albumin(all P<0.05).The predictive variables obtained by the LASSO regression analysis included sex,recurrent acute pancreatitis attacks,bile duct stones,peripancreatic fluid accumulation,pulmonary infection,pseudocysts,CRP,NLR,FIB,and LDL.The multivariate Logistic regression analysis showed that sex(odds ratio[OR]=2.716,P<0.05),recurrent acute pancreatitis attacks(OR=2.138,P<0.05),peripancreatic fluid accumulation(OR=2.297,P<0.05),pseudocysts(OR=2.805,P<0.05),and FIB(OR=1.313,P<0.05)were independent risk factors for CP complicated by PPH.The above factors were fitted into the model,and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787(95%confidence interval:0.730—0.844),and the calibration curve was close to the reference curve.The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting(χ2=7.469,P=0.487).The clinical decision curve analysis showed that the prediction model had good clinical practicability.Conclusion Male sex,recurrent acute pancreatitis attacks,peripancreatic fluid accumulation,pseudocysts,and FIB are independent risk factors for CP complicated by PPH,and the nomogram model established has good discriminatory ability,calibration,and clinical practicability.

Objective To evaluate the predictive performance of the Alberta stroke program early computed tomography score(ASPECTS),the Lausanne stroke scale(ASTRAL),DRAGON,START,and the total healthy risks for patients with vascular events calculated(THRIVE-c)score prediction models for the prognosis of patients with acute ischemic stroke(AIS)in Baoding advanced stroke centers,Hebei Province.Methods Clinical data of 909 patients with AIS who were admitted for intravenous thrombolysis in the department of emergency of the advanced stroke center of the Baoding NO.1 Central Hospital from January 2016 to August 2022 were collected and scored using the ASPECTS,ASTRAL,DRAGON,START,and THRIVE-c scales.The 3-month modified Rankin scale(mRS)score was observed for each score,with a score of 0-2 as a good prognosis and 3-6 as a poor prognosis,and multivariate Logistic regression coefficients for the variables in the 5 scores were compared with the original derivation cohort.The predictive efficacy of each scoring model for 3-month poor prognosis of AIS patients was analyzed by using the receiver operator characteristic curve(ROC curve),and area under the curve(AUC)was calculated;the degree of fit of each model to the actual prognostic results was assessed by using the Hosmer-Lemeshow goodness-of-fit test;at the same time,the calibration curves and Brier scores were used as an evaluation of the model's calibration performance indicators.Results A total of 786 patients were enrolled and 340 had a poor prognosis.Comparison of the validation cohort with the original cohort for model construction showed that the mean age in the validation cohort was 65 years old,with a relatively small proportion of 33.84%females,and a median glycemic value of 8.09 mmol/L.The proportion of poor prognosis was lower in the validation cohort compared to the original ASPECTS and THRIVE-c cohort(43.68%vs.51.90%,43.68%vs.50.30%)and higher in the validation cohort compared to the original cohorts of ASTRAL,DRAGON,and START(43.68%vs.34.00%,43.68%vs.35.20%,43.68%vs.39.10%,all P<0.05).ROC curve analysis showed that ASPECTS,ASTRAL,DRAGON,START and THRIVE-c scores all had predictive value for the prognosis of patients with AIS,with AUC and 95%confidence intervals(95%CI)of 0.848(0.820-0.876),0.825(0.795-0.855),0.833(0.805-0.861),0.838(0.811-0.866),and 0.727(0.691-0.762);in the anterior circulation it was 0.852(0.821-0.883),0.817(0.782-0.853),0.815(0.781-0.849),and 0.833(0.800-0.866),0.710(0.668-0.751);and 0.841(0.781-0.902),0.850(0.792-0.908),0.874(0.816-0.931),0.854(0.800-0.908),and 0.775(0.704-0.846)in the posterior loops,respectively.Hosmer-Lemeshow goodness-of-fit test showed that the DRAGON model curve had a smaller gap from the middle diagonal and was better calibrated(χ2=1.483,P=0.993).The Brier score showed that the ASPECTS scoring model had the smallest Brier score was 0.150 and the best performance.Conclusions The ASPECTS,ASTRAL,DRAGON,START,and THRIVE-c scoring models have been shown to be effective in predicting poor prognosis in patients with AIS treated with intravenous thrombolytic therapy at 3 months,with the ASPECTS model showing the most outstanding predictive performance.For anterior infarcts,the ASPECTS score demonstrated the highest predictive efficacy,whereas for posterior infarcts,the DRAGON score had the best predictive performance.The probability of the ASPECTS score in predicting prognosis in the prediction model was in good agreement with the actual probability.

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

OBJECTIVE: To explore the genetic basis for a child with metachromatic leukodystrophy (MLD). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Potential variant was screened by whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. The pathogenicity the variant was analyzed by multiple sequence alignment of the amino acid sequence and three-dimensional model prediction of its protein product. RESULTS: The child was found to harbor compound heterozygous variants c.257G>A (p.R86Q) and c.467del (p.G156Afs*6) of the ARSA gene, among which the c.467del (p.G156Afs*6) frameshift variation was unreported previously. Multiple sequence alignment showed that the site of the c.257G>A (p.R86Q) missense variant is highly conserved. Three-dimensional structure modeling analysis showed that the partial deletion due to the p.G156Afs*6 variant may cause significant alteration of the structure of ARSA protein. CONCLUSION The discovery of novel variant in ARSA has enriched the mutational spectrum of MLD and may facilitate the understanding of the genotype-phenotype correlation of MLD.
Cerebroside-Sulfatase/genetics* ; DNA ; Genetic Association Studies ; Humans ; Leukodystrophy, Metachromatic/genetics* ; Mutation

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of gastrointestinal tract, which mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). The existence of chronic diseases is an important influencing factor of sleep quality, and sleep quality is a key index to evaluate the quality of life. Sleep disorder can lead to fatigue, anxiety and stress. The incidence of sleep disorder in patients with active IBD is higher than that in remission IBD. When patients with IBD get worse, the sleep disorder is more serious, while sleep disorder can aggravate intestinal inflammation and injury recovery. This article summarized the research on the correlation between sleep disorder and IBD, and clarified their two - way interaction, so as to provide reference for the clinical management and treatment of sleep disorder associated with IBD.

Objective:To explore the effect of multi-channel health education model by professional team on drug compliance, disease knowledge and recurrence in rate of inflammatory bowel disease (IBD) patients, so as to provide basis for formulating scientific health education measures.Methods:From February 2016 to February 2019, IBD patients visited First Affiliated Hospital of Kunming Medical University were selected. According to whether they received health education, the patients were divided into intervention group (100 cases) and control group (138 cases). Morisky medication adherence scale-8 (MMAS-8) and Chinese version of Crohn′s and colitis knowledge score (CCKNOW) were used to evaluate treatment compliance and disease knowledge. The score of MMAS-8, the proportion of poor drug compliance, CCKNOW score and recurrence rate at 48 weeks of follow-up were compared between the intervention group and control group. Two sample t test and chi-square test were used for statistical analysis. Results:The total scores of MMAS-8 and CCKNOW of the intervention group were both higher than those of the control group (5.58±1.96 vs. 4.47±1.44, 10.87±4.21 vs. 9.23±4.65), and the differences were statistically significant ( t=-5.06 and -2.79, both P<0.05). The proportion of patients with poor drug compliance and recurrence rate at 48 weeks of follow up of the intervention group were both lower than those of the control group (56.0%, 56/100 vs. 86.2%, 119/138; 20.0%, 20/100 vs. 31.9%, 44/138), and the differences were statistically significant ( χ2=38.18 and 4.17, both P<0.05). Conclusions:Multi-channel health education by professional team can effectively improve the drug compliance and disease knowledge in IBD patients, improve patient self-management ability, and reduce the recurrence rate.

BACKGROUND: The Id2 gene is an endogenous negative regulator of basic helix-loop-helix factor, which is involved in the cell proliferation, differentiation and existence. Id2 also shows functional diversity in the progression and infiltration of different types of tumors OBJECTIVE: To observe the changes of proliferation and invasiveness of PC-3 human prostate cancer stem cells after shRNA-Id2 transfection. METHODS: PC-3 human prostate cancer stem cells in logarithmic growth phase were harvested to isolate tumor stem cell spheres by serum-free suspension culture. The expression of CD44+CD24-on the surface of tumor stem cells was detected by flow cytometry. The shRNA-Id2 expression vector was constructed and transfected into PC-3 human prostate cancer stem cells. Untransfected PC-3 human prostate cancer stem cells were used as control. At 48 hours after transfection, the expression of Id2 gene and protein in shRNA-Id2 transfected prostate cancer stem cells, NC-shRNA empty vector transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by RT-PCR and western blot, respectively. The proliferation and invasion of shRNA-Id2 transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by MTT assay and Transwell chamber, respectively. The expressions of E-cadherin, vimentin and Twist were detected by western blot and RT-PCR. RESULTS AND CONCLUSION: Tumor stem cell spheres were successfully isolated by the serum-free suspension culture. The expression rate of CD44+CD24-on the surface of the third-generation PC-3 human prostate cancer stem cells was (85.69±8.96) ％, indicating that the cultured tumor stem cell spheres overexpressed the phenotype of tumor stem cells. At 48 hours after transfection, the expression of Id2 gene and protein was significantly lower in the shRNA-Id2 transfection group than the non-transfection group (P < 0.05) , indicating that the expression of Id2 was successfully interfered with the expression of PC-3 prostate cancer stem cells. The invasive ability of the cells in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). Western blot and RT-PCR detection showed that the expression of E-cadherin, an epithelial marker of PC-3 prostate cancer stem cells, in the shRNA-Id2 transfection group was significantly higher than that in non-transfection group (P < 0.05) , while the expression of vimentin, a marker of mesenchymal stem cells, and Twist, a transcription factor regulating cell-mesenchymal transformation, in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). These findings indicate that RNA interference with Id2 gene can inhibit the proliferation and invasion of PC-3 prostate cancer stem cells by regulating the expression of E-cadherin, vimentin and Twist.