Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

ObjectiveTo observe the clinical efficacy and safety of Chaihu Shugansan combined with Xuanfu Daizhetang （CHSG-XFDZ） in the management of Barrett's esophagus （BE） with liver-stomach disharmony. MethodA randomized， parallel， controlled， double-blind clinical trial was conducted. BE patients who met the inclusion criteria were randomized into an observation group and a control group， with 34 patients in each group. The observation group was treated with CHSG-XFDZ combined with omeprazole capsules， and the control group was treated with CHSG-XFDZ mimetic combined with omeprazole capsules. Both groups were treated for 12 weeks. The traditional Chinese medicine （TCM） symptom scores， response rate， BE lesion area， BE pathological changes， and bile acid profile were taken as the indicators to jointly evaluate the clinical efficacy and safety of the two groups. ResultA total of 62 patients who completed the trial were included for statistical analysis， including 32 in the observation group and 30 in the control group. There were no statistically significant differences in baseline demographics or disease characteristics between two groups， which suggested that the two groups were comparable. The total response rate in the observation group was 93.7% （30/32）， which was higher than that （60.0%， 18/30） in the control group （χ²=24.766， P<0.05）. After treatment， the response rate regarding the pathological changes in the observation group was 62.5% （20/32）， which was higher than that （23.3%， 7/30） in the control group （χ²=10.270， P<0.05）. The response rate regarding the BE lesion area change in the observation group was 21.9% （7/32）， which had no statistically significant difference from that （6.7%， 2/30） in the control group， which indicated that the advantages of the two regimens were not obvious in terms of reducing the area of BE lesions. Compared with the control group after treatment， the observation group regulated the bile acid profile， which pointed out the direction for further exploring the mechanism of CHSG-XFDZ in treating BE. Neither group showcased adverse reactions with clinical significance during the treatment period. ConclusionCHSG-XFDZ outperformed the control group in terms of alleviating TCM symptoms， ameliorating pathological changes， and improving the bile acid profile in the BE patients with liver-stomach disharmony. It demonstrates certain potential in reducing the lesion area. This formula is safe and effective in treating BE patients with liver-stomach disharmony and deserves further clinical research and widespread application.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

With the development of more and more multi-center and cross-field cooperative medical research,the establishment of high-quality and efficient ethical collaborative review and mutual recognition systems is an inevitable demand for multi-institutional research,and an inevitable move to implement relevant national policies.Based on the work practice of ethical collaborative review and mutual recognition in Shenzhen,by analyzing the practical challenges of ethical collaborative review and mutual recognition in China,this paper proposed that to ensure the homogeneity and efficiency of review.Government departments need to take the lead,establish an ethical review alliance,and clarify responsibilities and rights.Based on actual needs,system first,and effective communication,ethical collaborative review and mutual recognition of results could be jointly promoted,aiming to provide a reference for our counterparts in China to promote ethical collaborative review and mutual recognition of cross-institutional research.

Objective To observe the application effect of montelukast sodium combined with terbutaline on cough variant asthma(CVA)in children and its influence on airway remodeling and peripheral blood inflammatory indicators.Methods The children with CVA were randomly classified into control group and treatment group.The control group was given aerosol inhalation of terbutaline(5 mg each time,twice a day),and on the basis of the control group,the treatment group was combined with oral administration of montelukast sodium granules(4 mg each time,once a day,taking before going to bed),and both groups were continuously treated for 3 months.The clinical efficacy,airway cross-section area(AO),airway lumen area(AI),airway wall thickness(T),airway wall area(WA),serum interleukin-5(IL-5),eosinophilic chemotactic factor(Eotaxin),macrophage inflammatory protein-1α(MIP-1α)and T lymphocyte subgroups CD4+,CD8+and CD4+/CD8+were compared between the two groups of children,and the medication safety was assessed.Results Fifty-three cases in control group and 53 cases in treatment group were included.After treatment,the total effective rates in treatment group and control group were 96.23％(51 cases/53 cases)and 83.02％(44 cases/53 cases),respectively(P＜0.05).The AO values in treatment group and control group were(39.42±3.67)and(45.69±4.92)mm2;AI values were(22.36±2.85)and(27.06±3.18)mm2;T values were(1.12±0.28)and(1.44±0.33)mm;WA values were(53.82±4.17)and(60.13±4.66)mm2;serum IL-5 levels were(25.46±5.83)and(41.46±7.64)ng·L-1;Eotaxin levels were(181.24±30.05)and(238.21±39.42)ng·L-1;MIP-1a levels were(15.24±3.67)and(22.43±4.05)ng·L-1;CD4+levels were(37.18±4.06)％and(33.57±3.82)％;CD8+levels were(24.08±3.15)％and(27.31±3.07)％;and CD4+/CD8+levels were 1.54±0.33 and 1.24±0.28,respectively(all P＜0.05).The total incidences of adverse drug reactions in treatment group and control group were 9.43％(5 cases/53 cases)and 3.77％(2 cases/53 cases),respectively(P＞0.05).Conclusion Montelukast sodium combined with terbutaline has an exact efficacy in the treatment of CVA in children,and it can effectively reverse airway remodeling,reduce inflammation level and enhance immune function,and it has good safety.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Histone deacetylases(HDACs)can deacetylate histones,leading to tighter DNA binding,and thereby playing a role in inhibiting gene transcription.On the contrary,histone deacetylase inhibitors(HDACis)can promote chromatin relaxation,enabling various transcription factors to bind specifically to DNA and activate transcription genes.Dental stem cells(DSCs)are human adult stem cells.These cells have the characteristics of less damage and low immune rejection during sampling,and are especially important seed cells in the process of osteogenesis,odontogenesis and other differentiation.A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation,signal transduction,regulation of cellular inflammation and other life processes.This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs,aiming to provide insights into the study of the interaction between HDACs and HDACis,and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.

Objective To analyze the influencing factors of pancreatic fat deposition in patients with type 2 diabetes mellitus(T2DM),and to explore the relationship between pancreatic fat deposition and islet function.Methods A survey on diabetes prevalence was conducted among 548 residents in the Nicheng community of Pudong New Area from October 2015 to December 2016,including 301 patients with T2DM and 247 subjects with normal glucose tolerance(NGT).General information of the subjects were recorded,blood biochemical and insulin indexes were measured,body composition was measured by dual-energy X-ray absorptiometry,and insulin resistance index(HOMA-IR)and islet cell sensitivity index(HOMA-β)were calculated.Fatty liver and pancreatic fat deposition were detected by ultrasound.Both the T2DM group and NGT group were further divided into two subgroups according to the pancreatic fat deposition.Differences in general demographic information,biochemical and body fat indices among the groups were compared.Multivariate logistic regression was used to analyze the influencing factors of pancreatic fat deposition.Results In the NGT group,the subgroup with pancreatic fat deposition showed higher levels of age,waist circumference,waist-to-hip ratio(WHR),body mass index(BMI),fasting insulin levels(FINS),2-hour postprandial insulin levels(2 h INS),triglycerides(TG),uric acid(UA),alanine aminotransferase(ALT),fatty liver prevalence,abdominal fat percentage,and abdomen-to-hip ratio(AHR),compared with the subgroup without pancreatic fat deposition.High-density lipoprotein cholesterol(HDL-C)and limb fat percentage were lower in the subgroup with pancreatic fat deposition.In the T2DM group,the subgroup with pancreatic fat deposition showed higher levels of waist circumference,BMI,FINS,2 h INS,TG,UA,ALT,aspartate aminotransferase(AST),fatty liver prevalence,and abdominal fat percentage,compared with the subgroup without pancreatic fat deposition,with statistically significant differences(P<0.05).The HOMA-IR and HOMA-β in both NGT and T2DM groups with pancreatic fat deposition were significantly higher than those in the groups without pancreatic fat deposition.The prevalence of insulin resistance also significantly increased,with statistically significant differences(P<0.05).The results of multivariate logistic regression analysis showed that HDL-C,HOMA-β,abdominal fat percentage,age and fatty liver were the influencing factors for pancreatic fat deposition in NGT.Conclusion Elderly individuals with abdominal obesity and fatty liver are more prone to developing pancreatic fat deposition,which can affect islet function and aggravate the insulin resistance.