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BACKGROUND: The comprehensive expression level and potential molecular role of Cyclin A2 (CCNA2) in uterine corpus endometrial carcinoma (UCEC) remains undiscovered. METHODS: UCEC and normal endometrium tissues from in-house and public databases were collected for investigating protein and messenger RNA expression of CCNA2. The transcription factors of CCNA2 were identified by the Cistrome database. The prognostic significance of CCNA2 in UCEC was evaluated through univariate and multivariate Cox regression as well as Kaplan-Meier curve analysis. Single-cell RNA-sequencing (scRNA-seq) analysis was performed to explore cell types in UCEC, and the AUCell algorithm was used to investigate the activity of CCNA2 in different cell types. RESULTS: A total of 32 in-house UCEC and 30 normal endometrial tissues as well as 720 UCEC and 165 control samples from public databases were eligible and collected. Integrated calculation showed that the CCNA2 expression was up-regulated in the UCEC tissues (SMD = 2.43, 95% confidence interval 2.23∼2.64). E2F1 and FOXM1 were identified as transcription factors due to the presence of binding peaks on transcription site of CCNA2. CCNA2 predicted worse prognosis in UCEC. However, CCNA2 was not an independent prognostic factor in UCEC. The scRNA-seq analysis disclosed five cell types: B cells, T cells, monocytes, natural killer cells, and epithelial cells in UCEC. The expression of CCNA2 was mainly located in B cells and T cells. Moreover, CCNA2 was active in T cells and B cells using the AUCell algorithm. CONCLUSION: CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC.

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BACKGROUND: Transcatheter arterial embolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC) patients while some HCC cases have shown resistance to TACE. AIM: To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC. METHODS: The microarray datasets of TACE-treated HCC tissues, HCC and non-HCC tissues were collected by searching multiple public databases. The respective differentially expressed genes (DEGs) were attained via limma R package. Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response. TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE non-response. The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model. The prognostic value of the key genes was evaluated by Kaplan-Meier curve. Multivariate analysis was utilised to investigate the independent prognostic factor in key genes. Single-cell RNA (scRNA) sequencing analysis was conducted to explore the cell types in HCC. TACE refractoriness-related genes activity was calculated via AUCell packages. The CellChat R package was used for the investigation of the cell-cell communication between the identified cell types. RESULTS: HCC tissues of TACE non-responders (n = 66) and TACE responders (n = 81), HCC (n = 3941) and non-HCC (n = 3443) tissues were obtained. The five key genes, DLG associated protein 5 (DLGAP5), Kinesin family member 20A (KIF20A), Assembly factor for spindle microtubules (ASPM), Kinesin family member 11 (KIF11) and TPX2 microtubule nucleation factor (TPX2) in TACE refractoriness-related genes, were identified. The five key genes were all up-regulated in the TACE non-responders group and the HCC group. High expression of the five key genes predicted poor prognosis in HCC. Among the key genes, TPX2 was an independent prognostic factor. Four cell types, hepatocytes, embryonic stem cells, T cells and B cells, were identified in the HCC tissues. The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells. Hepatocytes, as the providers of ligands, had the strongest interaction with embryonic stem cells that provided receptors. CONCLUSION: Five key genes (DLGAP5, KIF20A, ASPM, KIF11 and TPX2) were identified as promoting refractory TACE. Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

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Based on the service of stranded patients in D Hospital, this study aimed to explore the multiple needs of stranded patients and construct an intervention mode from the ecosystem perspective. Using the method of case study, taking the service of stranded patients in hospital D as an example, 49 case records and verbatim interviews with stakeholders were analyzed. The discharge and resettlement of stranded patients faces multiple obstacles from individuals, families, medical and social systems. This study constructed the social work intervention model from the ecosystem perspective: information collection and needs assessment, empowerment of individual system, reconstruction of family support system, coordination of medical system and linking social support system. The intervention process achieved efficient effects. Social work intervention of stranded patients should pay attention to patients’ psychosocial needs and improve awareness of system difficulties; mobilize the multi-system support network and deliver services in combination with case management method; conduct social advocacy for the breakthrough of law and policy.

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Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.

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OBJECTIVE To investigate the effects of matrine （MT） on steatosis Chang Liver cell model induced by oleic acid （OA） and its possible mechanism. METHODS Chang Liver cells were divided into blank group， model group and MT low-dose， medium-dose group and high-dose groups （0.1， 0.5， 1.0 mmol/L）. Except for blank group， the other groups were treated with 1.0 mmol/L OA for 24 h to establish steatosis model， and MT groups were given corresponding concentrations of drugs for 24 h. The activities of steatosis Chang Liver cells were observed； the morphologies of intracellular lipid droplets were observed and lipid content was also determined. The contents of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）]， as well as mRNA and protein expressions of farnesoid X receptor （FXR）， cytochrome P450 7A1 （CYP7A1） and fibroblast growth factor 19 （FGF19） were all detected. RESULTS OA and MT had no significant effect on the activity of Chang Liver cells. After OA treatment， orange lipid droplets formed in cytoplasm； compared with blank group， relative lipid content and the levels of liver function indexes were increased significantly， while the mRNA and protein expressions of FXR， CYP7A1 and FGF19 were down-regulated significantly （P＜0.05）. After treatment of low， medium and high concentrations of MT， above indexes were all reversed significantly （P＜0.05）. CONCLUSIONS MT could significantly improve the lipid content and liver function indexes of steatosis Chang Liver cells induced by OA though regulating FXR/CYP7A1/ FGF19 signaling pathway.

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Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

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Objective:To investigate the current situation of medical social worker supervision in Shanghai, for reference to promote the high-quality development of medical social work.Methods:From June to July 2022, a questionnaire survey was conducted on the in-service medical social workers in all medical institutions with medical social work departments or posts in Shanghai. The questionnaire mainly included demographic information, current status of supervision implementation, and effectiveness of supervision. The data were analyzed descriptively with t test for comparison between groups and the Pearson test was for correlation analysis. Results:A total of 99 medical social workers were included in this study, 65 had received supervision, and medical institutions where 58 people located had established the supervision system. The average scores of actual and expected supervisory support received by medical social workers were 3.71 and 4.20 respectively, and the mean burnout level score was 32.91. The effect of establishing a supervision institutions on burnout was statistically significant ( P<0.05) and actual access to supervision support was negatively associated with burnout ( P<0.05). Conclusions:The overall situation of medical social work supervision in Shanghai was positive, but the demand for supervision was not fully satisfied; Supervision had a positive impact on reducing the burnout level. It is suggested that medical social work should further strengthen the cultivation of supervisory talents, promote the construction of supervisory systems, and improve the quality of supervision.

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Objective To explore the association between triglyceride glucose(TyG)index and TyG-body mass index(TyG-BMI)and the prevalence of metabolic associated fatty liver disease(MAFLD)in the elderly men.Methods Totally 2290 elderly men were selected from January to December in 2021 in the Second Medical Center of Chinese PLA General Hospital,and divided into MAFLD group(n=1322)and non-MAFLD group(n=968).Multivariate logistic regression was used to analyze the association between TyG index,TyG-BMI and MAFLD.The receiver operating characteristic(ROC)curve was drawn to explore the predictive value of TyG index and TyG-BMI with MAFLD in the elderly men.Results Two thousand two hundred and ninety elderly men were(74.3±10.1)years old,and an average BMI of(24.63±2.70)kg/m2.BMI,γ-glutamyl transaminase(γ-GT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(Scr),thyroid stimulating hormone(TSH),free triiodothyronine(FT3),the rate of smoking and drinking,and the prevalence of hypertension,diabetes,hyperuricemia,high triglyceride(TG),low high density lipoprotein cholesterol(HDL-C),hyperuricemia,thyroid nodules and cholelithiasis were all significantly higher in non-MAFLD group than those in MAFLD group(P<0.05),while the age of MAFLD group was lower than that of non-MAFLD group(P=0.003).Multivariate logistic regression analysis showed that the risk of MAFLD in patients of TyG quartile groups Q2,Q3,Q4 was 1.667(95%CI 1.257-2.236,P<0.001),2.004(95%CI 1.482-2.710,P<0.001)and 5.420(95%CI 3.266-8.995,P<0.001)times higher than that of TyG Q1,respectively.The risk of MAFLD in patients of TyG-BMI Q2,Q3,Q4 was 2.215(95%CI 1.549-3.167,P<0.001),2.809(95%CI 1.723-4.580,P<0.001)and 2.513(95%CI 1.253-5.040,P=0.009)times higher than that of TyG-BMI Q1,respectively.The ROC curve showed that areas under the curve(AUC)of MAFLD predicted by TyG index and TyG-BMI were 0.717(95%CI 0.696-0.738)and 0.840(95%CI 0.823-0.856),and the best cut-off values were 8.63 and 205.20,respectively.Moreover,the ROC curve showed that AUC of MAFLD in the elderly men without hyperlipidemia or diabetes predicted by TyG index and TyG-BMI were 0.653(95%CI 0.622-0.684)and 0.840(95%CI 0.818-0.862),and the best cut-off values were 8.42 and 202.66,respectively.In addition,AUC,accuracy,specificity,sensitivity,positive predictive value and negative predictive value predicted by TyG-BMI were higher than those by TyG index.Conclusions TyG index and TyG-BMI are significantly associated with MAFLD in the elderly men.Both TyG index and TyG-BMI have certain predictive value for the prevalence of MAFLD in the elderly men,and TyG-BMI may be better.

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Metabolism-associated fatty liver disease(MAFLD),formerly known as non-alcoholic fatty liver disease(NAFLD),is one of the most popular chronic liver diseases in the world,and has become one of the main causes of liver cirrhosis,end-stage liver disease,and primary liver cancer.In recent years,the prevalence of MAFLD has gradually increased in China,the Asia Pacific region,and even globally,increasing the medical and socio-economic burden.The exploration of the epidemiology and risk factors of this disease at home and abroad has also gradually increased.Meanwhile,due to the scarcity of MAFLD treatment drugs,their drug treatment has become a hot issue that needs to be urgently addressed in clinical practice.In recent years,there has been an increase in the number of drugs entering the clinical trial stage.Based on this,the current epidemiological status,risk factors,diagnostic criteria,and treatment research progress of MAFLD have been reviewed in order to provide new ideas and directions for the clinical diagnosis,treatment,and scientific research of MAFLD.

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ObjectiveTo systematically review the effect of high-intensity interval training (HIIT) on executive function for healthy children and adolescents, and delineate the factors related to the intervention outcome. MethodsLiterature about the effect of HIIT on executive functions for healthy children and adolescent was retrieved from Web of Science, PubMed, Cochrane, Embase, Google Scholar, and CNKI, up to July 31st, 2023. The methodological quality was evaluated using the Physiotherapy Evidence Database (PEDro) scale, and relevant data were systematically reviewed. ResultsFifteen researches were included, from nine countries, comprising 13 randomized controlled trials with the scores of PEDro scale from five to eight, involving 17 021 participants aged six to 18 years. They were published mainly from 2016 to 2023. The primary factors related to the intervention outcome were the age of participants, HIIT intervention programs, and work-to-rest ratio. HIIT significantly improved working memory and inhibitory control in healthy children, while it was limited for adolescents. ConclusionHIIT can significantly improve inhibitory control and working memory in healthy children. Key factors related to the intervention outcomes include the age of participants and the specifics of the HIIT program, etc.

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The retention of emergency patients is a common problem faced by hospitals worldwide. In addition to medical problems, social, family, economic and other problems will also cause patients to stay in the emergency department. It not only brings challenges to patients’ own disease treatment and hospital operation and management, but also brings ethical dilemmas. Taking the service cases of medical social workers who involved in stranded patients in Shanghai E Hospital as an example, this paper analyzed 20 service records and interviews with social workers receiving cases, and combed the ethical dilemmas faced by medical social workers in the process of involving in emergency stranded patients. It was found that medical social workers faced many ethical dilemmas in the process of involving in emergency stranded patients, such as interpersonal relations and relevant legal regulations, the right to life and health and the right to informed consent, the self-determination of case owners and the allocation of medical resources. In this regard, it is suggested to solve the problem of patient retention by advocating the improvement of relevant systems and policies, building cooperative teams to smooth referral channels, strengthening education, and promoting family shared decision-making.

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Atherosclerosis is the main cause of cardiovascular diseases， while Carotid intima-media thickness is a biomarker of subclinical atherosclerosis. Numerous studies have confirmed that exercise can slow down or even reverse the formation and progression of carotid Intima-Media thickness. This paper provides a review of the effects of different exercise modalities， intensities， and populations on the vascular structure to provide a reference for the prevention of atherosclerosis with exercise.

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Background: The current study is the foremost study exploring the relationships between moderate-to-vigorous physical activity and health-related physical fitness indicators among 12-16-year-old adolescents of the South Punjab region of Pakistan. Methods: The researcher adopted the cross-sectional research design for the study. A total of 2970 participants (1477 boys and 1493 girls) aged adolescents from South Punjab, Pakistan, completed health-related physical fitness indicators measuring strength, endurance, and aerobic capacity through a hand-grip strength test, modified pull-up test, plank test, and 20-m shuttle run test, and physical activity were subjectively assessed by International Physical Activity Questionnaire Short Form (IPAQ-SF). Linear regression models were used to explore the between moderate-to-vigorous physical activity (MVPA) with health-related physical fitness indicators. Results: Positive associations were observed between hand-grip strength (p < 0.001), modified pull-up (p < 0.001), plank exercise (p < 0.001), and 20-m shuttle run test (p < 0.001), with MVPA. The gender-specific comparison also indicated a significant (p < 0.001) and positive relationship. The results revealed that as MVPA increases, body composition, muscular strength, core muscular endurance, and aerobic capacity could improve in both genders. Conclusions: MVPA appears to be an effective and reliable predictor of health-related physical fitness among school adolescents.

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BACKGROUND: Little is known about the relationship between integrin subunit alpha V (ITGAV) and cancers, including small cell lung cancer (SCLC). METHODS: Using large sample size from multiple sources, the clinical roles of ITGAV expression in SCLC were explored using differential expression analysis, receiver operating characteristic curves, Kaplan-Meier curves, etc. RESULTS: Decreased mRNA (SMD = - 1.05) and increased protein levels of ITGAV were detected in SCLC (n = 865). Transcription factors-ZEB2, IK2F1, and EGR2-may regulate ITGAV expression in SCLC, as they had ChIP-Seq (chromatin immunoprecipitation followed by sequencing) peaks upstream of the transcription start site of ITGAV. ITGAV expression made it feasible to distinguish SCLC from non-SCLC (AUC = 0.88, sensitivity = 0.78, specificity = 0.84), and represented a risk role in the prognosis of SCLC (p < 0.05). ITGAV may play a role in cancers by influencing several immunity-related signaling pathways and immune cells. Further, the extensive pan-cancer analysis verified the differential expression of ITGAV and its clinical significance in multiple cancers. CONCLUSION: ITGAV served as a potential marker for prognosis and identification of cancers including SCLC.

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Based on the service of stranded patients in D Hospital, this study aimed to explore the multiple needs of stranded patients and construct an intervention mode from the ecosystem perspective. Using the method of case study, taking the service of stranded patients in hospital D as an example, 49 case records and verbatim interviews with stakeholders were analyzed. The discharge and resettlement of stranded patients faces multiple obstacles from individuals, families, medical and social systems. This study constructed the social work intervention model from the ecosystem perspective: information collection and needs assessment, empowerment of individual system, reconstruction of family support system, coordination of medical system and linking social support system. The intervention process achieved efficient effects. Social work intervention of stranded patients should pay attention to patients’ psychosocial needs and improve awareness of system difficulties; mobilize the multi-system support network and deliver services in combination with case management method; conduct social advocacy for the breakthrough of law and policy.

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AIM: To study the effect and mechanism of Delicaflavone on migration and invasion of gefitinib-resistant lung cancer cell line PC-9/GR. METHODS: MTT assay was used to detect cell viability. Transwell and scratch assays were used to detect cell invasion and migration abilities. Western blotting was used to detect the expressions of MMP-9, MMP-2, E-cadherin, N-cadherin, Vimentin and PI3K/Akt/mTOR pathway-related proteins in PC-9/GR cells. RESULTS: Compared with control group, 20 mg/L Delicaflavone could significantly inhibit the viability of PC-9/GR cells for 24 h (P<0.05), while Delicaflavone below 10 mg/L had no significant effect on cell proliferation. The number of invasive cells and migrated cells were decreased significantly by Delicaflavone in a concentration-dependent way (P<0.05 and P<0.01). Delicaflavone could concentration-dependently reduce the expression of MMP-9, MMP-2, N-cadherin, vimentin (P<0.01), meanwhile up-regulate the expression of E-cadherin (P<0.01). In addition, Delicaflavone also decreased the expression of p-PI3K, p-Akt and p-mTOR in a concentration-dependent manner (P<0.01). CONCLUSION: Delicaflavone can inhibit the migration and invasion of PC-9/GR cells by regulating epithelial-mesenchymal transition via PI3K/Akt/mTOR pathway.

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Natural deep eutectic solvent (NDES) is a kind of deep eutectic solvents (DESs) which is composed of natural substances with good biocompatibility. Those substances can function as hydrogen bond donor and acceptor, such as choline, amino acids, sugars, etc. NDES have been widely used in many fields due to their advantages of low cost, easy preparation and environmental friendliness. It is especially suitable for the pharmaceutical industry because of its good biocompatibility and safety for use. In this paper, we firstly review the molecular simulation methods for current design of DESs from the formation principle. And then, the materials and preparation of NDES are reviewed and the physicochemical properties are further described. Finally, we review the current application of NDES in pharmaceutics including increasing drug solubility, promoting drug permeability and enhancing oral drug absorption, and meanwhile their future applications in pharmaceutics were also prospected.

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AIM: To construct and identify the mammary gland cell-specific conditional knockout of SENP7 by the Cre-loxP system. METHODS: The homozygous SENP7

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AIM: To investigate the mechanism of the involvement of SUMO-ylated Androgen receptor (AR) in tamoxifen resistance and the role of SUMO inhibitor ginkgolic acid in resistance. METHODS: Real-Time PCR was used to detect AR mRNA levels in parental cells MCF-7W and drug-resistant cells MCF-7R, AR protein levels and SUMO levels in MCF-7W and MCF-7R cells was performed by western blot, and CB/IP was applied to detect AR interacts with SUMOE3 ligase PIAS1 and HSP27 in MCF-7R cell chromatin, the transcriptional activity of SUMO AR was also evaluated by the fluorescent reporter gene experiment, the CCK-8 method and the trypan blue exclusion method were used to detect cell viability and cell viability respectively. RESULTS: The mRNA and protein expression levels of AR in MCF-7R cells were significantly higher than those in MCF-7W cells (P<0.05), and there was highly SUMOylated AR in MCF-7R cells. Further research found that there had an obvious interaction between AR and SUMO E3 ligase PIAS1 and HSP27, that was, the SUMOylated AR was modified by E3 ligase. Moreover, androgen R1881 could enhance the transcriptional activity of the SUMOylated AR in a concentration-dependent manner. Compared with ginkgo acid alone, 10 μmol/L of ginkgolic acid combined with 10 μmol/L of enzalutamide treated MCF-7R cells for 3 days, the cell number was significantly reduced, and the number of cell death increased significantly (P<0.05). CONCLUSION: The resistance mechanism of tamoxifen may be due to the enhanced AR transcription and activity increased by the hyperactive SUMOylated AR, SUMO inhibitor ginkgolic acid combined with AR antagonist enzalutamide can be a new strategy for the treatment of tamoxifen resistance.

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As a drug carrier, polymer microspheres have been widely used in oral drug delivery systems, which can achieve the purposes of protecting drug stability, slowing drug release, enhancing immunity, and improving drug absorption. The polymer materials used in the preparation of microspheres can be derived from natural substances, such as cellulose, polysaccharides, and proteins. These materials can also be derived from synthetic polymer substances, such as polycaprolactone and polylactic acid. In this paper, the role of microspheres in oral drug delivery and the types of oral microspheres were reviewed to provide references for in-depth research and development of oral microspheres.