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.

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

Objective:To preliminarily predict the potential pathways and targets of Xiaoban Tongmai Formula in anti-atherosclerosis(AS)by network pharmacology analysis,and to verify its possible mechanism combined with in vitro cell experiment.Method:The databases including Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GeneCards,Swiss Target Prediction,and Uniprot were used to collect the information on active compounds and corresponding targets of Xiaoban Tongmai Formula to construct the"compound-target-disease"network.The potential targets and pathways were predicted by protein-protein interaction(PPI)network,and the intersection targets were subjected to Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The human aortic vascular smooth muscle cells(HA-VSMCs)were cultured and identified in vitro,and the abnormal proliferation of HA-VSMCs were induced by oxidized low-density lipoprotein(ox-LDL)and identified;MTT method was used to detect the proliferation activities of the HA-VSMCs in various groups after treated with different concentrations of Xiaoban Tongmai Formula;the safety of Xiaoban Tongmai Fang was confirmed.The HA-VSMCs were divided into blank group,model group(the abnormal proliferation of HA-VSMCs was induced),rosuvastatin group(treated with 4 μmol·L-1 rosuvastatin after inducing the abnormal proliferation of HA-VSMCs),and low,medium,and high doses of Xiaoban Tongmai Formula groups(treated with 0.025,0.050,and 0.100 mng·L-1 Xiaoban Tongmai Formula after inducing the abnormal proliferation of HA-VSMCs);enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of monocyte chemotactic protein-1(MCP-1),interleukin-6(IL-6),and interleukin-8(IL-8)in supernatant of the HA-VSMCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of nuclear factor kappa-B(NF-κB)p65 mRNA and fibroblast growth factors 2(FGF2)mRNA in the HA-VSMCs in various groups;Western blotting method was used to detect the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in various groups.Results:Xiaoban Tongmai Formula contained 103 active ingredients that exert anti-AS effect by acting on 189 target genes.The potential targets included IL-6,IL-8,vascular endothelial growth factor A(VEGFA),nuclear factor kappa B1(NF-κB1),and RELA(NF-κB p65).The GO functional analysis and KEGG pathway enrichment analysis results showed that Xiaoban Tongmai Formula exerted anti-AS effects by regulating lipid metabolism,hypoxia-inducible factor-1(HIF-1),epidermal growth factor(EGF),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),and NF-κB signaling pathways.The cell morphology and immunofluorescence staining results confirmed that the cells were HA-VSMCs.The oil red O staining results showed numerous red lipid droplets,indicating successful modeling.The MTT assay results showed that Xiaoban Tongmai Formula had no significant effect on the proliferation rate of HA-VSMCs within a certain dose range,indicating good safety.The ELISA results showed that compared with model group,the levels of MCP-1 and IL-6 in supernatant of the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the levels of MCP-1 in supernatant of the HA-VSMCs in different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01).Compared with model group,the expression levels of NF-κB p65 mRNA in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression levels of FGF2 mRNA in the HA-VSMCs in rosuvastatin group and 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 and FGF2 mRNA in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.05 or P＜0.01).Compared with model group,the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased(P＜0.01);compared with rosuvastatin group,the expression levels of NF-κB p65 protein in the HA-VSMCs in 0.050 and 0.100 mg·L-1 Xiaoban Tongmai Formula groups were decreased(P＜0.01),and the expression level of FGF2 protein in the HA-VSMCs in 0.100 mg·L-1 Xiaoban Tongmai Formula group was decreased(P＜0.01).Conclusion:Xiaoban Tongmai Formula has anti-inflammatory effect,inhibitory effect on the proliferation of HA-VSMCs,and anti-AS effect,and its mechanism may be related to the inactivation of NF-κB/FGF2 pathway.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

Objective To explore the effects and influencing factors of traditional occupational health training on occupational health literacy (OHL) of employees in micro-, small- and medium-sized enterprises. Methods A total of 540 employees from 154 micro-, small- and medium-sized enterprises, who participated (347 employees) and not-participated (193 employees) in traditional occupational health training, and 171 community residents/students (not-participated in occupational health training) were selected as the research subjects using the convenient sampling method. The OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations. Results The overall OHL level of employees was 43.3% (234/540). Among them, the overall OHL level of untrained and trained employees was 38.9% and 45.8%, respectively, and the overall OHL level of community residents/students was 43.3%. The results of multivariate logistic regression analysis showed that the higher the educational level, the higher the OHL level (all P<0.01). The OHL level of untrained and trained employees was higher than that of untrained community residents/students (all P<0.05). The interaction of education level and training status had no statistical difference on the OHL level of the research subjects (P>0.05). The results of factorial design analysis of variance showed that the overall OHL score rate of untrained employees and trained employees was higher than that of untrained community residents/students (all P<0.05). However, there was no significant difference in overall OHL score rate between untrained and trained employees (P>0.05). Conclusion The role of traditional occupational health training in improving the OHL level of employees in micro-, small- and medium-sized enterprises needs to be improved. The responsibility of enterprise occupational health training should be implemented, and multiple measures should be taken to enrich the ways and approaches of occupational health education for enterprise employees, to effectively improve the OHL of workers.

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Topical anesthesia are being widely used in clinical diagnostic or therapeutic fields such as ophthalmology, ENT, dermatology, urology. It is defined as superficial loss of sensation in mucous membranes or skin, produced by direct application of penetrating local anesthetics. Topical anesthesia has the advantages of simple performance, high safety, quick recovery, which can effectively improve patient's satisfaction. In recent years, more and more attention has been paid to the concept of comfortable diagnosis and treatment. The new drugs and application methods of topical anesthesia are emerging constantly, special attention must be paid to their pharmacological characteristics and possible adverse reactions when using them. This article reviews the research progress of topical anesthesia in clinical application in order to provide reference for clinical practice.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.
Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome ; Humans ; Medicine, Chinese Traditional ; Precancerous Conditions/pathology* ; Stomach Neoplasms/pathology*

Vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. Traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Vascular Endothelial Growth Factor A