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.

AIM: To explore the control effects of wearing orthokeratology lens for 1 a on adolescent myopia patients with different diopters.METHODS: Prospective non-randomized controlled study. A total of 120 adolescent myopic patients(224 eyes), with an average age of 11.00±2.08 years old, who were fitted with orthokeratology lenses in the optometry department of our hospital from November 2022 to May 2023 were collected. There were 3 groups according to the spherical equivalent, including 86 eyes in the group of -0.50--2.00 D, 99 eyes in the group -2.25--4.00 D, and 39 eyes in group -4.25--6.00 D. Patients were followed up for 1 a to observe the changes of uncorrected visual acuity, axial length, corneal curvature, corneal central thickness and corneal endothelial cells density in the three groups after wearing lens for 1 a.RESULTS:A total of 113 cases(212 eyes)were followed up for 1 a, including 82 eyes in the group of -0.50--2.00 D, 95 eyes in the group of -2.25--4.00 D, and 35 eyes in the group of -4.25--6.00 D. There was no statistical difference in corneal central thickness and corneal endothelial cell density among the three groups of patients after wearing lens for 1 a(all P>0.05). Uncorrected visual acuity was significantly improved, and flat kerotometry(FK)and steep kerotometry(SK)were significantly flatter(both P<0.01). Furthermore, the growth of axial length in the three groups of patients after wearing lens for 1 a was 0.21±0.26, 0.13±0.21 and 0.09±0.10 mm, respectively(P<0.05). There were differences between the -0.50--2.00 D group and the -2.25--4.00 D group and -4.25--6.00 D group(P=0.028, 0.010), and there were no differences between the -2.25--4.00 D group and the -4.25--6.00 D group(P=0.344).CONCLUSION:It is safe and effective for young myopia patients to wear orthokeratology lenses, which can prevent the non-benign growth of the axial length and effectively delay the development of myopia, and the myopia control effect is better especially for myopia patients of above -2.0 D.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Objective:To investigate the clinical characteristics in older adult patients with sepsis and heart failure, and to analyze the influential factors of prognosis.Methods:Eighty-eight older adult patients with sepsis and heart failure who received treatment at Lishui Central Hospital from January 2020 to December 2022 were retrospectively included in the heart failure group. Eighty-eight older adult patients with sepsis, who did not have heart failure, were selected in a 1:1 ratio to form a non-heart failure group. Based on their survival status during hospitalization, the patients in the heart failure group were divided into two subgroups: the survival group and the death group. Logistic regression analysis was performed to identify the risk factors associated with the development of heart failure and adverse disease outcomes in older adult patients with sepsis.Results:There were no statistically significant differences in sex, smoking history, alcohol consumption history, history of hypertension, and history of diabetes between the heart failure group and the non-heart failure group (all P > 0.05). However, the proportion of patients aged 75 years or older in the heart failure group was 52.27% (46/88), which was significantly higher than the proportion in the non-heart failure group [34.09% (30/88), χ2 = 5.93, P < 0.05]. The proportion of patients with respiratory system infections in the heart failure group was 53.41% (47/88), which was significantly higher than the proportion in the non-heart failure group [29.55% (26/88), χ2 = 10.37, P < 0.05]. Logistic regression analysis showed that advanced age and respiratory system infections are independent risk factors for the development of heart failure in patients with sepsis. Among patients with sepsis and heart failure, 45 survived and 43 died, resulting in a mortality rate of 48.86%. The average age of patients in the death group was (76.27 ± 4.14) years, which was significantly higher than that in the survival group [(72.29 ± 4.06) years, t = 4.55, P < 0.05]. The brain natriuretic peptide level and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the death group were (636.70 ± 70.29) pg/mL and (31.93 ± 3.08) points, respectively, both of which were significantly higher than those in the survival group [(552.80 ± 54.66) pg/mL, (27.06 ± 3.80) points, t = 6.27, 6.59, both P < 0.05]. The lactate clearance rate and serum albumin level in the death group were (13.63 ± 4.84)% and (26.09 ± 4.77) g/L, respectively, both of which were significantly lower than those in the survival group [(19.94 ± 5.07)%, (30.55 ± 5.17) g/L, t = 5.97, 4.20, both P < 0.05]. Logistic regression analysis showed that in patients with sepsis and heart failure, advanced age, elevated serum brain natriuretic peptide levels, and high APACHE II scores are risk factors for poor prognosis and death. A high lactate clearance rate at 24 hours and elevated serum albumin levels are protective factors for survival. Conclusion:Advanced age and respiratory system infections increase the risk of heart failure in patients with sepsis. Advanced age, elevated brain natriuretic peptide levels, and high APACHE II scores are associated with an increased risk of death in these patients. High lactate clearance rates and elevated serum albumin levels are indicative of a reduced risk of death in patients with sepsis.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective This study aimed to investigate the levels of non-enzymatic antioxidants among patients with depression at different age stages.Methods One hundred thirty five patients with depression(including 63 elderly patients aged 60 years and older,and 72 young and middle-aged patients under 60 years old)and 98 healthy controls(including 46 elderly controls aged 60 years and older,and 52 young and middle-aged controls aged under 60 years old)were enrolled.Serum levels of non-enzymatic antioxidants(uric acid,total bilirubin,albumin)were assessed.Results Multiple analysis of variance showed the main effects of depression factors on uric acid and total bilirubin were significant(P<0.05).Uric acid[(314.30±85.18)μmol/L vs.(339.68±85.27)μmol/L],total bilirubin[(12.81±6.16)μmol/L vs.(15.09±5.97)μmol/L]levels were lower in patients with depression than in controls(P<0.05).There was an interactive effect between age and depression factors on the levels of albumin(P<0.001),and the levels of albumin[(41.05±3.97)g/L vs.(46.01±4.49)g/L]were lower in group of the elderly patients with depression than those in group of the young and middle-aged patients with depression(P<0.01).Conclusion Patients with depression have abnormalities in levels of non-enzymatic antioxidants which are more severe in elderly patients.

Macrophages are an important class of immune cells that are mainly derived from myeloid pro-genitor cells in the bone marrow.They function in phagocytosis and antigen presentation,and participate in innate immune and inflammatory responses.Lysophosphatidic acid (LPA) is an active phospholipid signaling molecule that induces macrophage differentiation and polarization,regulates macrophage migra-tion and infiltration,and modulates the inflammatory response in which macrophages participate.In this paper,we review the molecular mechanisms underlying the role of LPA in macrophages in recent years by taking the role of LPA in macrophages as an entry point:LPA plays an important role in macrophage dif-ferentiation and polarization by inducing related regulatory factors and cytokines;LPA receptors mediaterelated signaling pathways to regulate macrophage migration and infiltration;and the ATX/LPA signaling axis and related cytokines are involved in macrophage inflammatory regulation.In addition,the regulatory role and potential clinical value of LPA in tumor-associated macrophages and macrophage inflammatory response diseases are reviewed.At present,the molecular mechanism of action of LPA in macrophages has not been fully elucidated.And an in-depth study of the receptor expression,biological roles,and regulatory mechanisms of LPA in macrophages will provide new strategies for the treatment of macro-phage-associated diseases and cancers.

TGF-β1 is considered a key mediator in the formation of hepatic fibrosis and mainly acts by activating the downstream Smad signaling pathway.Smad2 and Smad3 are two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,while Smad7 is a negative-feedback regulator of the TGF-β1/Smad pathway and inhibits TGF-β1-mediated hepatic fibrosis.A growing number of studies are showing that natural products can delay the progression of hepatic fibrosis by regulating the TGF-β1/Smad pathway,inhibiting HSC activation,and reducing ECM deposition.This article reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in hepatic fibrosis,and summarizes the natural products that target the regulation of this pathway,providing a reference for research into the treatment of hepatic fibrosis.

In order to isolate Mycoplasma hyopneumoniae(Mhp)and select virulent strains with high growth titer from the isolates to acclimate at high temperature to obtain attenuated strains.Forty lung and trachea tissues were aseptically collected from pigs suspected of Mhp in several farms in Nanyang City.A total of 6 strains of Mhp were isolated through pathogen isolation,colony observation,PCR identification and sequencing.For each isolate,round colonies with neat edges,dewdrop like particles and ridges in the center were observed on solid medium.PCR could amplify the target gene bands of each isolated P36.After sequencing,the amplified products were compared with the gene sequences of ATCC 25934 reference strain(J strain)P36 registered in NCBI,and the homology was more than 99％.The growth titer of TH-1 strain measured by CCU experiment could reach 1011 CCU/mL,which showed a high growth titer.TH-1 strain was selected for continu-ous passage at high temperature(40 ℃)in vitro to obtain different passages(P50,P1 00,P1 50).TH-1 P150 still had a higher growth titer(1010 CCU/mL)at 40 ℃ growth temperature.TH-1 P1,P50,P100 and P150 were injected into the trachea to infect 25-day-old weaned piglets,and the re-sults of virulence evaluation showed that 4 pigs(4/5)in the P1 infection group had typical"meat or shrimp meat"lesions,and serious monocyte and lymphocyte infiltration were found in the lung HE pathological sections,and the cilia were clutter-tangled,shortened and exfoliated.P150 infec-tion group did not show typical Mhp characteristic lesions,lung HE and tracheal scan sections did not show microscopic pathological changes,indicating that TH-1 was a virulent strain,but its viru-lence was continuously decreased after continuous in vitro passage,and TH-1 P150 was a low-viru-lence strain.TH-1 P150 strain,as a attenuated vaccine strain,has good immunogenicity,and the av-erage reduction rate of pneumonia disease after immune challenge was 83.3％.In conclusion,a low-virulence strain with high growth titer(TH-1 P150)was obtained by continuous passage at high temperature in vitro for the first time,and its immunogenicity was good,which laid the foundation for further research and development of Mhp attenuated vaccine.