Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective To explore the syndrome characteristics of Henoch-Schonlein purpura nephritis in Shaanxi area;To provide reference for TCM clinical syndrome differentiation and treatment.Methods Clinical data on patients diagnosed with Henoch-Schonlein purpura nephritis who received outpatient or inpatient treatment at five hospitals in Shanxi area including Hospital of Shaanxi University of Chinese Medicine and Yulin Traditional Chinese Medicine Hospital etc from August 2020 to August 2022 were under retrospective collection.TCM syndrome distribution law in patients with Henoch-Schonlein purpura nephritis in Shaanxi area was concluded through frequency statistics,clustering analysis,principal component analysis,and complex network analysis.Results Totally 143 patients were included,involving 64 symptoms.3 groups of syndromes were obtained after clustering analysis,and principal component analysis was performed for each group of syndromes.Using complex network analysis and combining the results of clustering analysis and principal component analysis,classification groups for each group of main symptoms and comorbidities were formed,and their main syndrome classification was determined:qi-yin deficiency syndrome,accounting for 47.55％;spleen deficiency and dampness,accounting for 34.97％;wind-heat attacking the exterior,accounting for 17.48％.Conclusion The syndromes of Henoch-Schonlein purpura nephritis in Shaanxi area are mainly divided into three types:qi-yin deficiency,spleen deficiency and dampness and wind-heat attacking the exterior.Among them,qi-yin deficiency is the most common.

Objective To investigate mortality risk factors and characterize pathogen distribution and antimicrobial resistance patterns in intensive care unit(ICU)patients with suspected infection following surgery.Methods A total of 65 hospitals in 16 provinces in China from July 1,2021,to December 31,2022.Clinical data were collected for surgical patients transferred to the ICU with suspected infection.Data included demographics[sex,age,underlying conditions(hypertension,diabetes,cardiovascular/cerebrovascular disease,hematologic disease)],surgical site,infection site,microbiological results with susceptibility testing,drug resistance and acute physiology and chronic health evaluationⅡ(APACHEⅡ)scores and the length of hospital stays.Patients were stratified by prognosis into death group and survial group,by drug resistance status into resistant and non-resistant groups.Univariate and multivariate Logistic regression identified risk factors for mortality and antimicrobial resistance.Draw the receiver operator characteristic curve(ROC curve)to evaluate the predictive value of each risk factor for patient prognosis and drug resistance occurrence.Results A total of 677 patients with suspected postoperative infection in the ICU were enrolled.There were 96 deaths and 591 survivors.① Analysis of risk factors affecting prognosis:univariate analysis showed that compared with the survival group,the patients in the had a higher APACHEⅡscore,the proportion of patients with previous cerebrovascular disease,surgery sites in the abdomen,chest,brain,pelvis,limbs,other areas,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,Gram-positive bacterial infection(Candida),fungal infection,multi-drug resistant bacterial infection was higher,and the length of hospital stay was shorter(all P<0.05).Multivariate Logistic regression analysis identified higher APACHEⅡscore[odds ratio(OR)=1.15,95%confidence interval(95%CI)was 1.11-1.20],pulmonary infection(OR=4.07,95%CI was 2.05-8.11),bloodstream infection(OR=2.61,95%CI was 1.52-4.51),and urinary tract infection(OR=2.20,95%CI was 1.01-4.42)were independent risk factors for prognosis(all P<0.05).The ROC curve analysis showed that the death risk prediction model established based on the above independent risk factors had certain predictive value for the prognosis of ICU postoperative patients with suspected infection,area under the curve(AUC)=0.820,95%CI was 0.770-0.860,P<0.05.②Regarding antimicrobial resistance:250 patients developed resistance and 427 did not.Univariate analysis showed compared with the non-resistant group,the APACHEⅡscore,the proportion of patients with cerebrovascular diseases,hematological diseases,surgeries at chest,brain,limbs,other sites,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,intracranial infection,Gram-negative bacillus infection,and Gram-positive cocci infection(Staphylococcus epidermidis,Staphylococcus aureus,Enterococcus faecalis),and the mortality rate in the resistant group were significantly higher,the proportion of patients with surgeries at abdominal cavity,pelvic cavity and abdominal cavity infection were significantly lower,and the length of hospital stay was significantly longer(all P<0.05).Multivariate Logistic regression analysis bloodstream infection(OR=4.00,95%CI was 2.22-7.19),urinary tract infection(OR=3.25,95%CI was 1.47-7.17),Klebsiella pneumoniae infection(OR=2.23,95%CI was 11.22-44.02),Acinetobacter baumannii infection(OR=48.12,95%CI was 20.10-115.17),Pseudomonas aeruginosa infection(OR=34.06,95%CI was 13.00-89.25),Escherichia coli infection(OR=24.97,95%CI was 10.55-59.13),Stenotrophomonas maltophilia infection(OR=19.04,95%CI was 3.30-109.96),and Staphylococcus aureus infection(OR=13.48,95%CI was 4.57-39.78)were independent risk factors for resistance(all P<0.01).The ROC curve analysis showed that the predictive model for drug resistance established based on the above independent risk factors had certain predictive value for drug resistance in adult patients with suspected infections after surgery in the ICU.The AUC=0.920,95%CI was 0.890-0.940,P<0.05.Conclusion Higher APACHEⅡscores and the presence of pulmonary,bloodstream,or urinary tract infections were associated with increased mortality in ICU patients with suspected postoperative infection.Patients with bloodstream or urinary tract infections,or infections caused by Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Escherichia coli,Stenotrophomonas maltophilia,or Staphylococcus aureus,had significantly higher odds of developing antimicrobial resistance.

Objective:To evaluate the left atrial structure and function in patients with non-obstructive hypertrophic cardiomyopathy（NOHCM）and atrial fibrillation（AF）using four-dimensional automatic left atrial quantification（4D Auto LAQ）technology，and to explore the correlation between left atrial remodeling and AF.Methods:Ninety patients with NOHCM treated in the First Affiliated Hospital of Zhengzhou University from May 2023 to September 2024 were prospectively selected and divided into AF group（ n=27）and non-AF group（ n=63）according to whether they had AF. Clinical data of all enrolled patients were collected，and two-dimensional，color Doppler，and tissue Doppler ultrasound parameters were measured. 4D Auto LAQ technology was used to obtain left atrial volume and strain parameters. Inter-group comparison，univariate and multivariate Logistic regression analysis，and repeatability test were used to analyze the data. Results:Compared with non-AF group，left atrial maximum volume index（LAVImax），left atrial minimum volume index（LAVImin）and left atrial pre-systolic volume index（LAVIpreA）were increased in the AF group，but left atrial total ejection fraction（LAEF），left atrial passive ejection fraction（LApEF），left atrial active ejection fraction（LAaEF）and the absolute values of left atrial reservoir longitudinal and circumferential strains（LASr，LASr-c），left atrial conduit longitudinal and circumferential strains（LAScd，LAScd-c）and left atrial contraction longitudinal and circumferential strains（LASct，LASct-c）were decreased（all P<0.05）. Multivariate Logistic regression analysis showed that LAVImin was independently associated with AF（ OR=0.837， P<0.001）. Conclusions:4D Auto LAQ can quantitatively evaluate the left atrial structure and function in patients with NOHCM and AF，and LAVImin is independently associated with the presence of AF.

Objective To design a new type of elastic gloves for burn scar rehabilitation to solve the problems of conventional elastic gloves in pressure distribution,elasticity maintenance and absorption of sweat stains.Methods The new elastic gloves was made of non-woven fabric by spandex material,which was composed of external and internal parts.The main body of the external part was used as the primary structure of the gloves,which was provided with a sealing strip,a storage bag,a drawstring,etc.The internal part consisted of a bonding sheet,an elastic band,a fiber sheet,an absorbent sponge,some breathable holes,etc.Results The new elastic gloves designed could be used for the pressure therapy for the scars on the opisthenar,palm side,finger web and purlicue with scar proliferation inhibitted effectively,and the breathable hole and absorbent sponge contributed to the absorption of the sweat of the patient.Conclusion The new type of elastic gloves gains advantages in elasticity,wearing comfort and effectiveness of the pressure therapy for purlicue and finger web,and can be used for the pressure therapy to inhibit proliferative scarring after burns.[Chinese Medical Equipment Journal,2025,46(8):118-120]

Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.

Objective To explore the mechanism of Gandou Fumu Decoction(GDFMD)for improving Wilson's disease(WD)in tx-J mice.Methods With 6 syngeneic wild-type mice as the control group,30 tx-J mice were randomized into WD model group,low-,medium-and high-dose GDFMD treatment groups,and Fer-1 treatment group.Saline(in control and model groups)and GDFMD(3.48,6.96 or 13.92 g/kg)were administered by gavage,and Fer-1 was injected intraperitoneally once daily for 14 days.Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue;ALT,AST,albumin,AKP levels were determined to assess liver function of the mice.Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4,ACSL4,ALOX15,FTH1,FLT,TFR1,FAS,SCD1,and ACOX1,and Fe2+,MDA,ROS,SOD,GSH and 4-HNE levels were analyzed to assess oxidative stress.Results The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT,AST and AKP,decreased albumin level,increased Fe2+,MDA,ROS,4-HNE levels,decreased SOD and GSH levels(P<0.05),lowered protein expressions of ACOX1,GPX4,FTH1,FLT,FAS,and SCD1,and increased protein contents of TFR1,ACSL4 and ALOX15 in the liver.Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models,decreased the levels of Fe2+,MDA and ROS,increased SOD and GSH levels,and reversed the changes in hepatic protein expressions.Conclusion GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.