This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To establish a population pharmacokinetic(PPK)model of duloxetine in Chinese subjects.Methods Based on the data of intensive sampling of duloxetine hydrochloride enteric coated tablets in 36 healthy subjects after single/multiple administrations,a PPK model of duloxetine was established using NONMEM software.The effects of gender,age,body weight,albumin,serum creatinine,glutamic pyruvic transaminase and dose on pharmacokinetic parameters were investigated by stepwise forward and backward methods.Model validation includes goodness of fit,visual prediction check and bootstrap.Results The PPK model of duloxetine was a one compartment model with first-order elimination and the absorption characteristics were described by the transit model,and the dose was a covariate of clearance.The inter-individual variability of clearance,volume of distribution,mean transit time and number of transit compartments were 54.71％,56.86％,27.30％and 87.71％,respectively.Conclusion The transit model more reasonably describes the absorption characteristics of duloxetine in Chinese subjects.

ObjectiveTo analyze the surveillance status of acute respiratory tract infection pathogens in Fengxian District of Shanghai, and to determine the pathogen spectrum and epidemiological characteristics of acute respiratory tract infection in the district. MethodsCase surveillance data from Fengxian Central Hospital were collected through the Shanghai Integrated Surveillance System for Acute Respiratory Infections, and respiratory specimens were collected from the 50^th week of 2022 to the 49^th week of 2023 for nucleic acid detection of 25 pathogens and bacterial culture testing. Case surveillance data from Fengxian Central Hospital were collected through the National Influenza Sentinel Surveillance System, and respiratory specimens were collected for nucleic acid detection of 5 pathogens. ResultsThe percentage seeking for medical visits of influenza-like illness (ILI) and severe acute respiratory infection (SARI) were 4.74% and 0.81%, respectively, with epidemic peaks in winter and spring. A total of 1 610 samples were detected, among which 354 were SARI cases, whose age of P₂₅ and P₇₅ quartiles were 44 years and 71 years, respectively, with a positive detection rate of 48.31%. Among the 1 256 ILI cases, the age of P₂₅ and P₇₅ quartiles were 21 years and 39 years, respectively. The positive detection rate of pathogens was 65.04% in 123 ILI cases under comprehensive surveillance of respiratory tract infection and 66.11% in 1 133 ILI cases under influenza surveillance. The positive rates of influenza andSARS-CoV-2 in SARI samples were 12.99% and 29.66%, respectively. The positive rates of influenza and SARS-CoV-2 in ILI case samples were 33.20% and 31.53%, respectively. Influenza virus concentrated in the winter and spring. The ILI and SARI cases had the highest positivity rates in the 6‒14 years old group and 15‒24 years old group, respectively. ConclusionThe main pathogens of respiratory tract infection in Fengxian District of Shanghai were SARS-CoV-2 and influenza virus. Special efforts should be made to monitor respiratory disease pathogens in the population under 24 years old, and surveillance of SARI cases aged ≥60 years should be strengthened. The influenza virus and SARS-CoV-2 are alternating, which is different from the past and requires a change in the previous prevention and control strategies.

Objective:To investigate the diagnostic value of non-high-density lipoprotein cholesterol (non-HDL-C),ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and triglyceride glucose index (TyG) on metabolic syndrome (MS) in adult women.Methods:This was a cross-sectional study. A total of 24 410 adult women who received health examination in health management center of the Affiliated Hospital of Southwest Medical University were selected from January 2019 to December 2021 as subjects. The subjects′ basic information, physical examination results, and laboratory examination data were collected retrospectively. The relationship between non-HDL-C, TG/HDL-C, TyG, and MS in adult women were examined using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) were calculated to evaluate the diagnostic value of each indicator for MS in adult women.Results:Among 24 410 adult females, 800 (3.3%) were found to have MS. After adjusting for age, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, blood uric acid, history of hypertension, history of diabetes, fatty liver, non HDL-C ( OR=1.608), TG/HDL-C ( OR=1.311), TyG ( OR=13.288) were all risk factors for MS in adult women. non-HDL-C, TG/HDL-C, and TyG, as well as their combined AUC of ROC, were 0.795 (95% CI: 0.742-0.776), 0.909 (95% CI: 0.902-0.917), 0.942 (95% CI: 0.937-0.948), and 0.944 (95% CI: 0.937-0.950), respectively. TyG had the highest diagnostic value for MS in adult women among the three indicators, the optimal cutoff value for TyG was 8.237, with a sensitivity of 93.5% and a specificity of 85.5%. Conclusion:non-HDL-C, TG/HDL-C, TyG, as well as their combination, all demonstrate good diagnostic value for MS in adult women.

Chronic kidney disease(CKD)commonly used dietary assessments including 24-hour dietary recall(24 h DR)/3-day dietary recall(3DDR),food frequency questionnaire(FFQ),dietary records,and estimation of dietary protein intake based on nitrogen balance.Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method,it is crucial to develop an FFQ suitable for Chinese CKD patients.This review summarizes the advantages and disadvantages of dietary assessment methods for CKD,the current research status,and the content and steps involved in establishing an FFQ,with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

Primary liver cancer(PLC)is a common malignant tumor in China.It ranks second in the cause of tumor mortality and it is a serious threat to the lives and health of people.Transcatheter arterial chemoembolization(TACE)is the preferred treatment for patients with HCC who cannot be surgically cured,which is of great significance for prolonging the patient's life.However,the incidence of nausea and vomiting after TACE is very high,which is an important reason for the decline of patient treatment compliance,which seriously affects the quality of life and the effect of interventional therapy.This paper reviews the domestic and abroad literature concerning the nausea and vomiting in patients after TACE,focusing on the clinical features of nausea and vomiting,the risk factors and the assessment tools,so as to provide a scientific basis for clinical early identification and effective intervention of nausea and vomiting after TACE.(J Intervent Radiol,2024,33:565-570)

Objective To elucidate the mechanisms of interface disruption between the actin filament and membrane of the cell pseudopodium that occurs during the breakage of the pseudopodium.Methods Time-lapse images of the behavior of actin filaments and membranes during the rupture process of cell pseudopodia were captured using the confocal microscopy.A theoretical model of the fracture of a cylindrical interface was developed to analyze the interface damage between the actin filament and the membrane during the breakage of the cell pseudopodium.Molecular dynamics simulations were employed to simulate the breaking process of the cell pseudopodium for comparison with the theoretical results.A finite element model considering the coupling of the tensile and torsional deformation of actin filaments was developed to simulate the torsional deformation of actin filaments under tension,both in the presence and absence of a membrane.Results The theoretical results indicated an exponential relationship between the critical load for the broken interface and crack length.The critical load increased with the interfacial strength.The effect of the fiber diameter on the critical load depended on the crack length,exhibiting different effects for small and large crack lengths.Finite element analysis suggested that the membrane substantially constrained torsional movement when the actin filament was extended.Conclusions This study revealed the breaking process of cell pseudopodia and the mechanical aspects underlying the disruption of the interface between the actin filament and the membrane.These results provide theoretical support for exploring cellular behaviors associated with pseudopodium breakage,such as the release of extracellular vesicles.