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 effect of curcumin on the growth of malignant glioma and the possible mecha-nism.Methods Human glioblastoma cell U87 was taken as the study object.They were randomly separa-ted into the blank control group(without any interven-tion)and low,medium and high curcumin group(10,20 and 40 μmol·L-1),temozolomide group(40μmol·L-1),curcumin 40 μmol·L-1+LY210976110 μmol·L-1,curcumin 40 μmol·L-1+SRI-011381 10 μmol·L-1,then they were intervened for 48 h.The activity,migration and invasion ability of U87 cells in each group were measured by CCK-8 method and Transwell method.The cell cycle changes of U87 cells were measured by flow cytometry.The ex-pression levels of TGF-β1/Smad signaling pathway in U87 cells were measured by Western blotting.Results After 48 h intervention,the percentage of U87 cell activity,cell migration and invasion number in curcu-min group and temozolomide group were lower than those in the blank control group(P＜0.05),and all decreased with the increase of curcumin dose(P＜0.05).Compared with the blank control group,the number of cells increased in Sub-G0 stage in the curcu-min group and temozolomide group(P＜0.05),and decreased in G2/M stage(P＜0.05).The protein rel-ative expression levels of TGF-β1,p-Smad 3,N-cad-herin,matrix metalloproteinase(MMP)-2 and MMP-9 in U87 cells in high curcumin group and temozolomide group were lower than those in the blank control group(P＜0.05),and the protein relative expression levels of Smad 7 and E-cadherin were higher than those in the blank control group(P＜0.05).There was no statisti-cally significant difference between the high curcumin group and temozolomide group(P＞0.05).Compared with the high curcumin group,inhibition of TGF-β1/Smad pathway could further inhibit the activity,migra-tion and invasion of U87 cells,reduce the relative ex-pression levels of TGF-β1,P-Smad 3,MMP-2 and MMP-9 proteins(P＜0.05),and increase the relative expression levels of Smad 7 and E-cadherin protein(P＜0.05),while the TGF-β1/Smad pathway activator was vice versa(P＜0.05).Conclusions Curcumin can inhibit the growth of malignant glioma U87 cells,and the mechanism may be related to the regulation of TGF-β1/Smad signaling pathway.

This study was aimed at analyzing the molecular epidemiological characteristics of all 14 cases of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018,to provide a scientific basis for prevention,control,and treatment.The genomic sequence was obtained through high-throughput gene sequencing after nucleic acid extraction.Homolo-gy analysis,evolution analysis,mutation locus analysis,and homology modeling were performed in bioinformatics analysis software.The nucleotide homology and amino acid homology of the HA gene in 14 human infected H7N9 viruses were(97.39％-100％)and(98.38％-100％),respectively.The nucleotide homology of the NA gene and the amino acid homology ranged from 97.73％to 100％.All viruses were low pathogenic avian influenza viruses belonging to the Yangtze River Delta lin-eage and were divided into two subclades,which were most similar to the A/Hunan/02650/2016 vaccine strain.All HA pro-teins G186V and T160A were mutated;13 strains of Q226L were mutated;and none of the four key neuraminidase inhibitor resistance sites of NA protein were mutated.All sites of M2 protein S31N and V27A were mutated,all sites of PB1 protein T368V were mutated,and all sites of PA protein K356R were mutated.Xinjiang H7N9 virus exhibited double receptor bind-ing,and was resistant to amantadine drugs and sensitive to neuraminidase inhibitors,which may be used in early disease sta-ges.Strengthened monitoring and timely detection of avian in-fluenza virus genome changes will be critical for prevention and control,and formulation of countermeasures.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective:To investigate the value of 18F-FDG PET/CT combined with conventional imaging modalities in the evaluation of the depth of tumor invasion, regional lymph node metastasis, distant organ and lymph node metastasis (TNM staging), and the adjacent structure invasion of rectal cancer. Methods:Fifty-four patients (28 males, 26 females, age (65.8±11.0) years) with pathologically confirmed rectal cancer admitted to the Affiliated Qingdao Central Hospital of Qingdao University between September 2019 and June 2021 were retrospectively analyzed. 18F-FDG PET/CT examination, conventional imaging modalities including high-resolution MRI (HR-MRI), chest CT plain scan, upper abdominal MRI or CT plain scan+ enhanced examination were performed within 2 weeks before or after the rectal cancer being confirmed. The TNM staging and adjacent structural invasions including circumferential resection margin (CRM), extramural vascular invasion (EMVI), anal sphincter complex involvement were evaluated by 18F-FDG PET/CT and conventional imaging modalities separately or in combination, and those results based on imaging were compared with the pathological results or clinical follow-up results. χ2 test was used to compare the differences of diagnostic sensitivity, specificity and accuracy between the 18F-FDG PET/CT or conventional imaging modalities and combined examination. Results:The accuracy for T staging and the sensitivity and accuracy for N staging of the combined examination were 96.30%(52/54), 98.65%(73/74) and 93.91%(185/197), respectively, which were significantly higher than those of 18F-FDG PET/CT (85.19%(46/54), 66.22%(49/74), 81.73%(161/197); χ2 values: 3.97, 26.88, 13.66, all P<0.05). The specificity (91.06%, 112/123) and accuracy of the combined examination for N staging were higher than those of the conventional imaging modalities (77.24%(95/123), 83.76%(165/197); χ2 values: 8.81, 10.23, both P<0.05). The sensitivity and accuracy of the combined examination for M staging were higher than those of the conventional imaging modalities (97.01%(65/67) vs 73.13%(49/67), 95.95%(71/74) vs 68.92%(51/74); χ2 values: 15.05, 18.66, both P<0.001). The sensitivities of the combined examination in evaluating CRM and EMVI were 100%(22/22) and 95.00%(19/20), and the accuracies were 98.15%(53/54) and 96.30%(52/54), all of which were higher than those of 18F-FDG PET/CT (CRM: 54.55%(12/22), 74.07%(40/54); EVMI: 30.00%(6/20), 74.07%(40/54); χ2 values: 12.94, 13.08, 18.03, 10.56, all P<0.01). The accuracy of the combined examination in evaluating EMVI was higher than that of the conventional imaging modalities (85.19%(46/54); χ2=3.97, P=0.046). Conclusion:18F-FDG PET/CT combined with conventional imaging modalities can improve the diagnostic efficacy for TNM staging and assessment of adjacent structural invasion in rectal cancer.

The research progress in key technologies for dynamic perception of battlefield casualties was reviewed,including unmanned equipment dynamic mapping,dynamic environment semantic segmentation and casualty detection and identification.The discussion also covered the current state of research on casualty dynamic perception equipment in aerial and ground domains.The development trends of key technologies and equipment for dynamic perception of battlefield casualties were pointed out,and references were provided for enhancing the efficacy of battlefield casualty care and improving medical service support capabilities.[Chinese Medical Equipment Journal,2024,45(9):95-108]

Objective:To investigate the chemotherapy pass rate and interleukin(IL)-17/IL-23 axis of Kanglaite injection combined with anlotinib and DC chemotherapy in the treatment of non small cell lung cancer (NSCLC).Methods:The clinical data of 103 NSCLC patients admitted to Suzhou Hospital Affiliated to Anhui Medical University (Suzhou Municipal Hospital) from January 2021 to December 2022 were selected retrospectively, and they were divided into observation group (52 cases) and control group (51 cases) based on the treatment plan. The patients in the two groups were given DC chemotherapy, and on this basis, the control group was given arotinib, while the observation group was given arotinib combined with Kanglaite injection. Three weeks′treatment was one cycle, and the two groups were treated for 3 consecutive cycles. The total clinical response rate, chemotherapy delay rate and chemotherapy pass rate after treatment were compared between the two groups, and the levels of neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), IL-17 and IL-23 were compared between the two groups before chemotherapy and at the end of each chemotherapy cycle. The incidence of adverse reactions after treatment was compared between the two groups, and the improvement rate of Karnofsky Performance Status Score (KPS score) after chemotherapy was compared.Results:The total clinical response rate in the observation group was higher than that in the control group: 61.54%(32/52) vs. 41.18%(21/51), there was statistical difference ( χ2 = 4.27, P<0.05). At the third cycle of chemotherapy, the delay rate of chemotherapy in the observation group was lower than that in the control group : 1.92% (1/52) vs. 15.69% (8/51), and the chemotherapy pass rate was higher than that in the control group: 92.31% (48/52) vs. 76.47% (39/51), there were statistical differences ( χ2 = 4.51, 4.92, P<0.05). The serum levels of NSE, CYFRA21-1, CEA, IL-17 and IL-23 in the observation group were lower than those in the control group at the first, second and third cycles of chemotherapy ( P<0.05). The incidence of myelosuppression and gastrointestinal adverse reactions in the observation group were lower than those in the control group: 19.23% (10/52) vs. 45.10% (23/51), 59.62% (31/52) vs. 86.27% (44/51), there were statistical differences ( χ2 = 7.91, 9.24, P<0.05). The improvement rate of KPS score in the observation group was higher than that in the control group after chemotherapy: 51.92% (27/52) vs. 29.41% (15/51), there was statistical difference ( χ2 = 5.40, P<0.05). Conclusions:Anlotinib and DC chemotherapy combined with Kanglaite injection can effectively regulate tumor related cytokine levels, reduce adverse reactions, improve chemotherapy pass rate and treatment effect. It may be related to downregulating the IL-17/IL-23 axis.

Objective To analyze the current state of medication literacy among elderly patients with chronic diseases in urban areas of Beijing,identify its key influencing factors,and propose targeted improvement measures.Methods From February 1 to June 30,2023,a questionnaire survey was conducted among elderly chronic disease patients in 193 communities across 15 districts of Beijing using a convenience sampling method.Data was collected through face-to-face interviews,with a total of 787 questionnaires distributed and 755 valid responses received.The logistic regression analysis model was employed to systematically identify and evaluate the factors affecting patients'medication literacy.Results Among the 755 valid questionnaires collected,53.25%(402 cases)of patients met the medication literacy criteria.Regression analysis results showed that multiple factors significantly influenced medication literacy among elderly patients with chronic diseases,including using rural cooperative medical care or self-payment methods(OR=1.669,P=0.039),retaining medication instructions(OR=0.519,P=0.038),checking medication instructions before use(OR=1.993,P<0.01),and possessing the ability to understand medication instructions(partial understanding OR=2.805,P=0.038;fully understanding OR=3.084,P=0.022)as positive influencing factors;whereas having 2 to 3 chronic diseases(OR=0.574,P=0.039),taking 3 to 5 medications(OR=1.845,P=0.015),and experiencing drug-related problems(OR=1.993,P<0.01)were identified as negative influencing factors.Conclusion Multiple factors influence medication literacy among elderly patients with chronic diseases.To ensure the safety and efficacy of their medication use,It is recommended to implement targeted measures.These include revising patient medication guidance leaflets tailored to age,enhancing patients'understanding of drug instructions,and strengthening medication guidance and social support systems.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.