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: To understand the unhealthy listening habits and related factors hearing on impairment among primary and middle school students in Jilin Province, so as to provide a scientific basis for the prevention of hearing impairment in children and adolescents. Methods: From September to November 2021, a stratified cluster random sampling method was employed to select 12 847 primary and middle school students in nine cities of Jilin Province who use headphones for more than 0.5 hours daily for a questionnaire survey. Data on unhealthy listening habits, lifestyle habits and hearing impairment were collected. The data were analyzed using the χ 2 test and Logistic regression. Results: Totally 1 702 students(13.25%) experienced hearing impairment within the last month. There were statistical differences between the sexes with the average daily headphone use, the times of using headphones ≥1 h every day for one week use in all environment or noisy environment ( χ 2=47.86, 57.60, 66.31, P <0.01). Logistic regression analysis results showed that factors related to the occurrence of hearing impairment among primary and secondary school students included:average daily headphone use of 1-2 h and more than 2 h ( OR=1.74, 95%CI =1.60-1.90; OR=1.73, 95%CI =1.59-1.90), times of using headphones ≥1 h every day for one week were 1-2 times and >2 times ( OR=1.71, 95%CI =1.59- 1.84 ; OR=1.83, 95%CI =1.71-1.97), the times of using headphones≥1 h every day for one week being 1-2 times and >2 times in noisy environment per week ( OR=1.48, 95%CI =1.40-1.56; OR=1.72, 95%CI =1.61-1.86), economic underdevelopment ( OR=1.85, 95%CI =1.76-1.96), boarding （OR=1.78, 95%CI =1.69-1.89), single parent family ( OR=1.72, 95%CI =1.60- 1.87 ), daily activity duration less than 1 h ( OR=1.71, 95%CI =1.63-1.81), sedentary behavior duration more than 6 h per day ( OR=1.88, 95%CI =1.79-1.98) ( P <0.05). Conclusions The behavior of ear protection among primary and middle school students in Jilin Province needs to be enhanced, focusing on students in economically underdeveloped areas, boarding schools and single parent families. It is necessary to guide primary and middle school students to improve their bad ear habits, increase outdoor activities and reduce the time of sitting.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Objective:To investigate the expression of RAD18 in colon cancer and its correlation with proliferating cell nuclear antigen (PCNA).Methods:The glass slice of colon cancer tissues and adjacent normal tissues from patients (73 cases) who underwent surgical treatment at the Second Hospital of Tianjin Medical University from November 2013 to November 2023 were collected.The expression of RAD18 in colon cancer tissues and adjacent normal tissues was analyzed in the gene expression profiling interactive analysis (GEPIA) database and verified by immunohistochemical staining. The relationship between RAD18 expression and clinicopathological features of colon cancer patients was analyzed. HCT116 and HT29 cells were cultured in vitro, and the control group and transfection group ( transfected with RAD18 shRNA to knock down RAD18 ) were set up. The expression of RAD18 was evaluated by quantitative real-time PCR (qRT-PCR) and Western Blot. The effect of RAD18 on colon cancer cell proliferation was explored using clonogenic assays and cell counting Kit-8 (CCK-8) assays. The correlation between RAD18 and PCNA was investigated by GEPIA and immunohistochemical staining. Results:The GEPIA database analysis showed that the expression of RAD18 in colon cancer tissue ( n = 275) was significantly higher than that in adjacent normal tissues ( n = 349, P < 0.05). RAD18 was expressed at higher levels in colon cancer tissue than that in adjacent normal tissues and was not expressed at high levels in the latter. The expression of RAD18 was closely related to tumor size in the low-expression group and high-expression group of patients ( P = 0.015) but was not related to age ( P = 0.115), gender ( P = 0.665), or tumor differentiation ( P = 0.733). Compared with the control group, the expressions of RAD18 in the transfection group of HCT116 and HT29 cells were both reduced (both P < 0.05). Compared with the control group, the clone cell number and absorbance ( A) value of HCT116 and HT29 cells in the transfection group were decreased (all P < 0.05). GEPIA database analysis showed that RAD18 was correlated with PCNA ( R = 0.27, P < 0.05), and the expression level of PCNA was higher in colon cancer tissues than in adjacent normal tissues. Conclusions:RAD18 is expressed at a higher level in colon cancer tissues and may promote colorectal cancer proliferation by affecting PCNA.

Objective To explore the effect of cardiac shock wave therapy(CSWT)on ST deviation of electrocardiogram and myocardial perfusion imaging in coronary artery disease(CAD)patients.Methods CAD patients who received CSWT in Cardiology Department of Beijing Hospital from December 2016 to August 2022 were enrolled.Three months of CSWT were conducted with a total of 9 times shock wave treatment.Clinical data,myocardial perfusion imaging data and stress electrocardiogram data were collected.Myocardial perfusion score,electrocardiographic data were compared before and after CSWT.Results A total of 55 patients were finally enrolled.There were 43 male and 12 female patients with an average age of(67.45±8.96)years old.ST deviation on 12 leads of electrocardiogram did not show significant difference before and after CSWT.Myocardial perfusion imaging showed global stress perfusion score(P=0.031)and reverse perfusion score(P=0.024).Global rest ischemia score reduced after CSWT(P=0.034).Target stress perfusion score(P=0.002),target reverse perfusion score(P=0.002),target reverse ischemic area(P=0.001)were improved after CSWT.Conclusions CSWT may not influence ST deviation of electrocardiogram,but may improve myocardial ischemia in CAD patients,

This study investigated the prevalence of Borrelia burgdorferi,Anaplasma phagocy tophilum,Rickettsia typhi,Orientia tsutsugamushi,Leptospira interrogans,Francisella tularensis,and Babesia spp.in small mammals in the Qinghai plateau region,to provide a scientific basis for the prevention and control of local zoonotic diseases.Small mammals were cap-tured with snap traps at six sampling sites in the Qinghai plateau region.Liver,spleen,and kidney tissues were collected for detection of six bacterial pathogens with real-time PCR.Conventional PCR(cPCR)was used for Babesia detection,and the positive PCR products were sequenced and analyzed.The differences in pathogen detection rates among species and habitats were analyzed with x2 test or Fisher's exact test.In to-tal,235 small mammals from 15 species were captured.B.burgdorferi,L.interrogans,and Babesia were detected in 11 spe-cies of small mammals,whereas A.phagocytophilum,R.typhi,O.tsutsugamushi,and F.tularensis were not detected.B.burgdorferi was detected in 41 small mammals from nine species(Cricetulus longicaudatus,Apodemus peninsulae,Ochotona curzoniae,Mus m usc ulus,Meriones meridians,Microtus arvalis,Cricetidae,Ochotona cansus,and Allactaga sibirica),with an infection rate of 17.45％(41/235).L.interrogans was detected in eight small mammals from four species(C.longicaudatus,M.musculus,M.arvalis,and Microtus oeconomus),with an infection rate of 3.40％(8/235).Babesia was detected in only one Mustela altaica,with an infection rate of 0.85％(1/235).Statistically significant differences were ob-served in the detection rates of pathogens among small mammal species(x2=200.54,P＜0.05).Among habitats,the detection rate of B.burgdorferi was highest in the forest(Fisher's exact test,P＜0.05).B.burgdorferi and L.interrogans co-infection was observed in three M.arvalis and two C.longicaudatus.In addition,one Babesia sequence was obtained,which clustered with Babesia vulpes in the phylogenetic tree.B.burgdorferi,L.interrogans,and Babesia were the main pathogens prevalent in small mammals in the Qinghai plateau region and have potential to cause human diseases.Local authori-ties should strengthen the surveillance of corresponding zoonotic diseases,and formulate corresponding prevention and control measures.

Objective:In order to construct a multisectoral cooperation evaluation index system for chronic disease prevention and control in the Healthy China strategy,so as to provide a reference for the evaluation and improvement of multisectoral cooperation work.Methods:The initial indicator system was constructed based on D'Amour's cooperative structure model.Fifteen public health experts were selected to refine the evaluation indicators through two rounds of expert consultation using the Delphi method.Then weights of indicators were assigned according to AHP.Results:Experts'positive coefficient,level of authority and coordination of opinions were confirmed.The finalized evaluation index system for multisectoral cooperation in chronic disease prevention and control contains 5 first-level indicators,12 second-level indicators and 34 third-level indicators.According to the weight,the indicators in first level were Shared Goals and Vision(0.222 8),Internalization(0.158 7),Formalization(0.252 3),Governance(0.154 5)and Cooperation effects(0.211 8).Conclusions:The evaluation index system applicable to multisectoral cooperation in the prevention and control of chronic diseases in counties(cities/districts)is preliminarily established,which is highly scientific and operable,and lays the foundation for the next step of application and promotion.

Objective:To explore the value of circ_0054633 in early diagnosis and prognosis prediction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children with severe pneumonia.Methods:A retrospective case-control study was conducted on children with diagnosed severe pneumonia admitted to Tianjin Children's Hospital from July 1, 2022, to February 29, 2024. The clinical data was collected by electronic medical record system and clinical follow-up, including gender, age, lung injury prediction score (LIPS), pediatric critical illness score (PCIS), serum circ_0054633, interleukin-6 (IL-6), the indicators of the arterial blood-gas analysis, oxygenation index (PaO 2/FiO 2) within 24 hours of admission and the survival status of 28 days. According to whether ALI/ARDS occurred, they were divided into the ALI/ARDS group and the non-ALI/ARDS group. The differences of clinical data between the two groups were compared, and multivariate Logistic regression was used to analyze the risk factors for ALI/ARDS in children with severe pneumonia. The receiver operator characteristic curve (ROC curve) will be used to explore the early diagnostic value of ALI/ARDS in children with severe pneumonia. The patients of ALI/ARDS were divided into mild group, moderate group and severe group according to the level of PaO 2/FiO 2. The levels of serum circ_0054633 and IL-6 in various severity ALI/ARDS were compared. The differences of serum circ_0054633, IL-6 levels, PCIS score and LIPS score were compared between the two groups of ALI/ARDS patients according to different prognoses in 28 days, as well as the correlation between various risk factors and circ_0054633. Results:A total 74 children with severe pneumonia were included, with 34 cases in the ALI/ARDS group and 40 cases in the non-ALI/ARDS group. In ALI/ARDS group, there were 9 cases in the mild group, 15 cases in the moderate group and 10 cases in the severe group; while 12 cases died and 22 cases survived after 28 days. The serum circ_0054633, IL-6 level and LIPS score were higher in the ALI/ARDS group than the non-ALI/ARDS group, while the PCIS score was lower, and the two groups had significant difference. Multivariate Logistic regression analysis showed that circ_0054633 was independent predictors of ALI/ARDS in children with severe pneumonia [odds ratio ( OR) = 3.853, 95% confidence interval (95% CI) was 1.912-7.805, P = 0.017]. ROC curve analysis showed that the cut-off values for circ_0054633 in the diagnosis of ALI/ARDS were 3.955, sensitivity was 79.4%, specificity was 92.5%, area under the ROC curve (AUC) was 0.892. The serum circ_0054633 and IL-6 levels were higher in the children who died in 28 days than the children who were survived, while the PCIS score was lower, and the two groups had significant difference. Spearman correlation analysis showed that the level of circ_0054633 in children with ALI/ARDS was positively correlated with 28-day mortality and IL-6 ( r value was 0.675, 0.763, respectively, all P < 0.001), but negatively correlated with PCIS score ( r = -0.626, P < 0.001), while no significant correlation with LIPS score ( r = 0.389, P = 0.023). Conclusion:The level of serum circ_0054633 has a better value in early diagnosis and prognosis prediction of ALI/ARDS caused in children with severe pneumonia.

Objective:To analyze the clinical phenotype and genetic characteristics of probands in 3 pedigrees of complex hereditary spastic paraplegia type 5 (HSP5) who developed symptoms during childhood, and the genetic diagnostic methods of HSP5 to improve the diagnosis and differential diagnosis of this disease.Methods:The clinical data of 3 HSP5 families admitted to Henan Provincial People′s Hospital from June 2020 to January 2023 were collected. Whole exome sequencing (WES) was performed on the patients to analyze phenotype-related single nucleotide variation (SNV) and small fragment insertion/deletion (INDEL) variation. At the same time, the sequencing data were used to analyze the dynamic mutation regions of specific genes.Results:The probands in the 3 families had complex HSP: the proband in family 1 showed weakness of both lower limbs, urgency of urination and ataxia; the proband in family 2 showed slightly lower intelligence, weakness of both lower limbs, dysarthria, and brain magnetic resonance imaging showed white matter lesions; the proband in family 3 showed muscle weakness, spasm, frequent urination and ataxia of both lower limbs. The sequencing results showed that the CYP7B1 gene c.1171G>T (paternal) and c.1249C>T (maternal) compound heterozygous mutations were found in proband 1 and his younger brother. The CYP7B1 gene c.334C>T (paternal) and c.259+2T>C (maternal) compound heterozygous mutations were found in proband 2 and her younger sister. The CYP7B1 gene c.334C>T (paternal) and c.1082G>A (maternal) compound heterozygous mutations were found in proband 3. And c.1171G>T was a new variant that had not been reported before. Dynamic mutation analysis showed that the numbers of CAG repeats of ATXN1/2/3/6/7/8/12, DRPLA, TBP genes were within the normal range. According to the clinical manifestations and genetic examination results of the children in the 3 pedigrees, the diagnosis of HSP5 was clear. Conclusions:The 3 families in the study all had complex HSP5 caused by compound heterozygous mutations of the CYP7B1 gene. WES can analyze SNV, INDEL and dynamic mutations simultaneously to make the maximum clear diagnosis and can be used as an effective detection method for HSP5.

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.