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.

Purpose To investigate the expression of fuma-rate hydratase(FH)and 2-succinocysteine(2SC)in leiomyoma with singular nuclear features,and to analyze the diagnostic val-ue of these two proteins in fumarase hydratase-deficient(FH-d)uterine leiomyomas.Methods Sixty-seven cases of leiomyoma with singular nuclear features were collected.The expression was detected by immunohistochemical EnVision method,and the relationship between the expression of FH,2SC and the morpho-logical characteristics of FH-d uterine leiomyomas was analyzed,and the relevant literature was reviewed.Results There were 67 patients of leiomyoma with singular nuclear features,among which 27 had FH-d leiomyoma.The positive rate of FH was(2/27,7.41％),significantly lower than that of leiomyomas without FH-d(31/40,77.50％).The positive rate of 2SC(26/27,96.30％)was significantly higher than that of leiomyo-mas without FH-d(11/40,27.50％).The statistical results showed that there was a correlation between the expression of FH and 2SC(P＜0.05);positive expression of FH and 2SC was associated with significant eosinophilic nucleoli,perinucleolar vacuoles,eosinophilic inclusions and antler vessels(P＜0.05).The sensitivity and specificity of FH immunohistochemi-cal identification of FH defective leiomyoma were 92.59％and 77.50％,respectively.The sensitivity and specificity of 2SC immunohistochemical were 96.30％and 72.50％for FH defec-tive leiomyomas,respectively.Conclusion In most leiomyomas with FH-d morphology,FH expression is negative and 2SC ex-pression is positive.The combined detection of FH and 2SC can significantly improve the diagnosis of FH defective leiomyoma.

Objective:To clarify the spatio-temporal characteristics and changing trends of provincial health resources and medical pressure,and to provide suggestions for the high-quality development of medical and health services in China.Methods:Based on the panel data of 31 provincial administrative units from 2010 to 2020,a comprehensive evaluation system of provincial health resources and medical pressure was constructed.The global entropy method and exploratory spatial analysis were used to reveal the spatio-temporal differentiation and correlation pattern,and the Tapio decoupling index was illustrated to explain the evolution characteristics and trends.Results:During the observation period,health resources and medical pressure in the vast majority of provinces in China rose steadily,with positive spatial correlation and agglomeration,and a close relationship with economic development and population demand;the mainstream decoupling state of the country shifted from a negative decoupling to a positive decoupling,with an obvious progressive decoupling trend,and the development of regional health continued to improve.Conclusions and suggestions:Provinces need to take into account the status quo of health development in their own provinces,focus on the spatio-temporal coupling of elements and structures,and optimize the structure of health resource allocation and enhance the resilience of the health system as a means of bringing into play the comparative advantages of the regional health system.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Lactic acid produced by muscles during exercise training is transported to the liver for metabolism through the bloodstream.In this process,the lactate acid level increases with the increase of exercise intensity,and the concentration of lactate acid in interstitial matrix of muscle tissues increases subsequently,leading to muscle fatigue.Transcutaneous electrical nerve stimulation(TENS)is a widely used medical method for muscle relaxation and improving peripheral blood circulation.To monitor the potential of TENS to alleviate muscle fatigue,this study adopted electrical impedance tomography(EIT)method to visualize the alleviating effect of TENS on muscle fatigue by detecting the tissue electrical characteristics response caused by the changes in blood lactate concentration,a biomarker of muscle fatigue.An experimental platform was thus constructed to mimic the changes of blood lactate concentration(Cbl)in the muscle tissue model,and to measure the trend of the spatial-mean conductivity((σ))in the mimic model during the Cbl change.The blood flow velocity was closely related to the metabolic rate of the lactate in the blood.TENS could speed up blood flow and effectively reduced the lactate accumulation in muscle tissue.However,too fast blood flow velocity was prone to cause secondary ventricular fibrillation disease,which threatened the safety of human life.To avoid this threat,a real-time blood flow velocity mimic platform was developed in this study to monitor the(σ)changes caused by the changes in blood flow velocity(vph)in the vicinity of mimic blood vessels.The correlations between Cbl vs(σ),and vph vs(σ)in the mimic muscle tissue were verified by Pearson test.Pearson correlation analysis results showed a positive correlation between Cbl and(σ)(r=0.9113,p<0.05),and betweenvph and(σ)(r=0.9782,p<0.001).The approach presented here quantitatively assessed the potential of TENS stimulation-induced changes in lactate concentration and blood flow velocity for alleviating muscle fatigue through(σ).

Functional gastrointestinal disorders(FGIDs)are common digestive system diseases in children,which can severely affect the growth and development of infants and toddlers.Probiotics therapy,as a relatively safe treatment method,have attracted the attention of researchers.However,their effectiveness in treating FGIDs in infants and toddlers is still unclear.This article reviews the mechanisms of probiotics in treating FGIDs in infants and toddlers,explores the reasons for the inconsistency in various research results,and aims to provide assistance for the clinical treatment of FGIDs in infants and toddlers and future research.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Functional near infrared spectroscopy(fNIRS)is an emerging neuroimaging tool that reflects the activity and function of brain neurons by monitoring changes in brain oxygen metabolism based on the neurovascular coupling mechanism.It is non-invasive and convenient,especially suitable for monitoring neonatal brain function.This article provides a comprehensive review of research related to the developmental patterns of brain networks concerning language,music,and emotions in neonates using fNIRS.It also covers brain network imaging in neonatal care,resting-state brain network connectivity patterns,and characteristics of brain functional imaging in disease states of neonates using fNIRS.