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.

Based on the data from the 5^th National Physical Fitness Surveillance in China, this study aimed to explore the relationship between abnormal body weight and physical fitness levels in older adults.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To explore the differences in clinical efficacy between Co-Cr-Mo guided multidirectional sliding growing rod technology (CMSG) and traditional growing rod in the treatment of neurofibromatosis type 1 dysplastic early-onset scoliosis.Methods:A retrospective analysis was conducted on the data of 20 patients with neurofibromatosis type 1 dysplastic early-onset scoliosis who underwent surgical treatment in the Scoliosis Department of Zhengzhou Orthopaedic Hospital Affiliated to Henan University from January 2010 to July 2022. There were 10 patients in the traditional rod group (treated with traditional growing rod surgery) and 10 patients in the CMSG group (treated with CMSG technology). All patients were ≤10 years old and had a Cobb angle ≥45°. The number of surgeries and the occurrence of complications were recorded. The Cobb angle of the main scoliotic curve, the Cobb angle of kyphosis from T 5 to T 12, and the height from T 1 to S 1 were measured from the imaging data to evaluate the correction of deformity and spinal growth. Results:There were no significant differences in age, gender, follow - up time, preoperative Cobb angle, and preoperative Cobb angle of kyphosis from T 5-T 12 between the CMSG group and the TGR group ( P>0.05). The number of surgeries 1.3±0.67 and the total medical cost 91, 100±34, 700 yuan in the CMSG group were lower than those in the TGR group (5.3±1.77 times and 155, 800±45, 900 yuan], and the differences were statistically significant ( t=6.687, P<0.001; t=3.558, P=0.002). The Cobb angles of the main curve before surgery, after the first surgery, and at the last follow - up in the CMSG group were 69.7°±17.8°, 19.8°±9.7°, and 24.4°±9.0° respectively, while those in the TGR group were 62.0°±11.1°, 32.1°±11.4°, and 33.3°±11.6° respectively. The differences in Cobb angles after the first surgery and at the last follow-up between the two groups were statistically significant ( t=2.633, P=0.017; t=2.313, P=0.033). The Cobb angles of kyphosis from T 5 to T 12 before surgery, after the first surgery, and at the last follow - up in the CMSG group were 40.0°±24.2°, 21.0°±6.0°, and 33.6°±9.3° respectively, while those in the TGR group were 31.3°±14.5°, 26.3°±10.5°, and 32.3°±17.2° respectively. There were no significant differences in the Cobb angles of kyphosis from T 5 to T 12 after the first surgery and at the last follow-up between the two groups ( t=1.383, P=0.184; t=0.243, P=0.811). The heights from T 1 to S 1 before surgery, after the first surgery, and at the last follow-up in the CMSG group were 30.5±3.4 cm, 33.7±3.3 cm, and 37.9±4.8 cm respectively, with an annual increase of 1.18±0.39 cm. The heights from T 1 to S 1 in the TGR group were 29.1±3.0 cm, 31.4±2.9 cm, and 36.3±3.5 cm respectively, with an annual increase of 1.25±0.23 cm. There was no significant difference in the annual growth height of T 1-S 1 between the two groups ( t=1.367, P=0.189). During the follow-up period, 3 patients in the CMSG group had 3 complications: 1 case of coronal plane trunk decompensation, 1 case of rod fracture, and 1 case of distal junctional kyphosis. In the TGR group, 7 patients had 8 complications: 2 cases of wound rupture, 3 cases of screw loosening, 1 case of distal addition phenomenon, 1 case of proximal addition phenomenon, and 1 case of rod fracture. Conclusion:The Co-Cr-Mo guided multidirectional sliding growing rod technique is safe and effective in treating type 1 neurofibromatosis with malnutrition type early-onset scoliosis. It can effectively control the progression of spinal deformities,preserve the growth ability of the spine, and have a low overall incidence of complications.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To explore the differences in clinical efficacy between Co-Cr-Mo guided multidirectional sliding growing rod technology (CMSG) and traditional growing rod in the treatment of neurofibromatosis type 1 dysplastic early-onset scoliosis.Methods:A retrospective analysis was conducted on the data of 20 patients with neurofibromatosis type 1 dysplastic early-onset scoliosis who underwent surgical treatment in the Scoliosis Department of Zhengzhou Orthopaedic Hospital Affiliated to Henan University from January 2010 to July 2022. There were 10 patients in the traditional rod group (treated with traditional growing rod surgery) and 10 patients in the CMSG group (treated with CMSG technology). All patients were ≤10 years old and had a Cobb angle ≥45°. The number of surgeries and the occurrence of complications were recorded. The Cobb angle of the main scoliotic curve, the Cobb angle of kyphosis from T 5 to T 12, and the height from T 1 to S 1 were measured from the imaging data to evaluate the correction of deformity and spinal growth. Results:There were no significant differences in age, gender, follow - up time, preoperative Cobb angle, and preoperative Cobb angle of kyphosis from T 5-T 12 between the CMSG group and the TGR group ( P>0.05). The number of surgeries 1.3±0.67 and the total medical cost 91, 100±34, 700 yuan in the CMSG group were lower than those in the TGR group (5.3±1.77 times and 155, 800±45, 900 yuan], and the differences were statistically significant ( t=6.687, P<0.001; t=3.558, P=0.002). The Cobb angles of the main curve before surgery, after the first surgery, and at the last follow - up in the CMSG group were 69.7°±17.8°, 19.8°±9.7°, and 24.4°±9.0° respectively, while those in the TGR group were 62.0°±11.1°, 32.1°±11.4°, and 33.3°±11.6° respectively. The differences in Cobb angles after the first surgery and at the last follow-up between the two groups were statistically significant ( t=2.633, P=0.017; t=2.313, P=0.033). The Cobb angles of kyphosis from T 5 to T 12 before surgery, after the first surgery, and at the last follow - up in the CMSG group were 40.0°±24.2°, 21.0°±6.0°, and 33.6°±9.3° respectively, while those in the TGR group were 31.3°±14.5°, 26.3°±10.5°, and 32.3°±17.2° respectively. There were no significant differences in the Cobb angles of kyphosis from T 5 to T 12 after the first surgery and at the last follow-up between the two groups ( t=1.383, P=0.184; t=0.243, P=0.811). The heights from T 1 to S 1 before surgery, after the first surgery, and at the last follow-up in the CMSG group were 30.5±3.4 cm, 33.7±3.3 cm, and 37.9±4.8 cm respectively, with an annual increase of 1.18±0.39 cm. The heights from T 1 to S 1 in the TGR group were 29.1±3.0 cm, 31.4±2.9 cm, and 36.3±3.5 cm respectively, with an annual increase of 1.25±0.23 cm. There was no significant difference in the annual growth height of T 1-S 1 between the two groups ( t=1.367, P=0.189). During the follow-up period, 3 patients in the CMSG group had 3 complications: 1 case of coronal plane trunk decompensation, 1 case of rod fracture, and 1 case of distal junctional kyphosis. In the TGR group, 7 patients had 8 complications: 2 cases of wound rupture, 3 cases of screw loosening, 1 case of distal addition phenomenon, 1 case of proximal addition phenomenon, and 1 case of rod fracture. Conclusion:The Co-Cr-Mo guided multidirectional sliding growing rod technique is safe and effective in treating type 1 neurofibromatosis with malnutrition type early-onset scoliosis. It can effectively control the progression of spinal deformities,preserve the growth ability of the spine, and have a low overall incidence of complications.