The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

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 investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective To design a lightweight and modular air container-based bio-isolated transfer and treatment device for efficient,safe and reliable treatment and evacuation of massive infectious patients.Methods The device had an ISO 668 40 ft(1 ft=30.48 cm)standard container as its body,which was made of aluminum alloy plate,new low-density heat preservation material and medical fireproof board,and its wall was manufactured using aluminum alloy honeycomb plate,fireproof insulation material and interior panel.The main components of the device included a negative-pressure control and envoiron-mental control system,a life support system,an intelligent control and information interaction system and a comprehensive support system.The negative-pressure control and envoironmental control system was composed of a distributed power supply ventilation system without air ducts and an intelligent control system for gradient pressure difference,the life support system was made up of a treatment module,a support module and a medical technical module,the intelligent control and information interaction system comprised a container information auto monitoring and interaction module,a multi-mode communication module and a telemedicine module,and the comprehensive support system consisted of a power supply module,a water supply and drainage module and an oxygen supply module.Results The device proved to behave better than the containerized biocontainment system of the U.S.army in key indictors,which could be used for long-voyage transmodality and treatment for massive infectious patients.Conclusion The device developed gains advantages in biosafety and life support,which facilitates all-domain transmodality of infectious patients while meeting the demand for rapid air transportation and treatment.[Chinese Medical Equipment Journal,2024,45(12):19-24]

Objective To design a lightweight and modular air container-based bio-isolated transfer and treatment device for efficient,safe and reliable treatment and evacuation of massive infectious patients.Methods The device had an ISO 668 40 ft(1 ft=30.48 cm)standard container as its body,which was made of aluminum alloy plate,new low-density heat preservation material and medical fireproof board,and its wall was manufactured using aluminum alloy honeycomb plate,fireproof insulation material and interior panel.The main components of the device included a negative-pressure control and envoiron-mental control system,a life support system,an intelligent control and information interaction system and a comprehensive support system.The negative-pressure control and envoironmental control system was composed of a distributed power supply ventilation system without air ducts and an intelligent control system for gradient pressure difference,the life support system was made up of a treatment module,a support module and a medical technical module,the intelligent control and information interaction system comprised a container information auto monitoring and interaction module,a multi-mode communication module and a telemedicine module,and the comprehensive support system consisted of a power supply module,a water supply and drainage module and an oxygen supply module.Results The device proved to behave better than the containerized biocontainment system of the U.S.army in key indictors,which could be used for long-voyage transmodality and treatment for massive infectious patients.Conclusion The device developed gains advantages in biosafety and life support,which facilitates all-domain transmodality of infectious patients while meeting the demand for rapid air transportation and treatment.[Chinese Medical Equipment Journal,2024,45(12):19-24]

Objective Observe the effect of Liuwei Anshen Capsule on sleep improvement of aged sleep deprivation zebrafish model.Methods Sixty 18-month-old female zebrafish were randomly divided into blank group,model group,Liuwei Anshen group,and melatonin group.The zebrafish in the blank group were raised under normal lighting conditions,and the other three groups were constructed with continuous lighting for 3 days.Zebrafish in Liuwei Anshen group were treated with Liuwei Anshen capsule water solution 0.000 50 mg·mL-1 for 3 days on the basis of model group,and zebrafish in melatonin group were treated with melatonin aqueous solution 0.2 mg·mL-1 on the basis of model group for 3 days.After 3 days,the zebrafish behavior system was used to detect the resting time of zebrafish in each group.qRT-PCR method was used to detect cyclin 1a(per1a),cyclin2(per2),circadian motor output cycle 1a(clock1a),cryptochrome 1b(cry1b),and 5-hydroxyindoleacetic acid(5-htiaa)in each group of zebrafish and follicle-stimulating hormone beta(fshβ)gene expression levels.Western blot was used to detect the expression levels of estrogen receptorα(Esrα),Fshβand luteinizing hormone(Lh)in zebrafish in each group.HE staining was used to observe the ovary of zebrafish in each group.Results Compared with the zebrafish in the blank group,the resting time of the zebrafish in the model group decreased significantly(P<0.01)during the 24 hours of observation.After the intervention of Liuwei Anshen Capsule and melatonin,the resting time of the zebrafish was significantly increased.(P<0.01).Compared with the zebrafish in the blank group,the mRNA expressions of zebrafish circadian clock genes per1a,per2,clock1a,cry1b,5-htiaa,and fshβ all showed a downward trend after sleep deprivation(P<0.05,P<0.01).After the intervention of Liuwei Anshen Capsules,the mRNA expressions of per1,clock1a,cry1b,5-htiaa and fshβ were all up-regulated(P<0.05,P<0.01).Compared with the zebrafish in the blank group,the protein expressions of Esrα and Lh in the zebrafish of the model group were up-regulated(P<0.05),the expression of Fshβ protein was down-regulated(P<0.05),after the intervention of Liuwei Anshen Capsules,the above proteins did not change significantly.The ovarian tissue cells of the zebrafish in the blank group had normal morphology and a large number of primary oocytes,while the ovarian tissue cells of the zebrafish in the model group were damaged in morphology and the number of primary oocytes decreased,after the intervention of Liuwei Anshen Capsule and melatonin,the cell morphology of zebrafish ovarian tissue was still damaged to varying degrees,but the whole was relatively intact,and the number of primary oocytes increased.Conclusion The insomnia of aged zebrafish may be caused by multiple factors.Liuwei Anshen capsule has significant effects on estrogen level of rhythm gene and ovarian function of sleep-deprived aged zebrafish.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Objective To investigate the clinical efficacy of low-dose plasma exchange (PE) combined with artificial liver in the treatment of acute-on-chronic liver failure (ACLF) and its effect on mortality rate after stratification. Methods A total of 272 ACLF patients who were admitted to Department of Infection and Hepatology, The First Affiliated Hospital of Kunming Medical University, from January 2018 to December 2020 were enrolled and divided into low-dose PE+double plasma molecular absorption system (DPMAS)/hemoperfusion (HP) group ( n =190) and medical treatment group( n =82). Laboratory markers were collected before and after treatment, and clinical outcome was compared between the two groups; stratified analysis (early stage, early-middle stage, late stage or types A, B, C) was performed for the two groups according to Diagnostic and treatment guidelines for liver failure (2018 edition), and all patients were followed up to observe general status and death at 12 weeks (short-term) and 48 weeks (long-term) after discharge. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the paired samples t -test was used for comparison before and after treatment; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Wilcoxon test was used for comparison before and after treatment; the chi-square test was used for comparison of categorical data between groups. Results Both low-dose PE combined with DPMAS/HP and medical treatment alone could reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase, total bilirubin (TBil), and blood ammonia and increase the level of albumin (Alb), and both groups had significant changes in these indices after treatment (all P < 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP better reduced ALT, TBil, and blood ammonia and improved Alb, with significant changes in these indices after treatment (all P < 0.05). Low-dose PE combined with DPMAS/HP could significantly reduce bile acid, international normalized ratio, neutrophil-lymphocyte ratio, and MELD score and increase platelet-to-white blood cell ratio (all P < 0.05), while medical treatment alone could not improve the above indices (all P > 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP could reduce the short-term mortality rate of ACLF patients, especially the short-term mortality rate of ACLF patients with early-stage, early-middle-stage or type A ACLF, and there were significant differences between the two groups (all P < 0.05). In the low-dose PE+DPMAS/HP group, the patients with early-stage ACLF had significantly lower short- and long-term mortality rates than those with late-stage ACLF, and the patients with type A ACLF had significantly lower short- and long-term mortality rates than those with type C ACLF (all P < 0.05). Conclusion Low-dose PE combined with DPMAS/HP has good clinical efficacy and can effectively reduce the short-term mortality rate of ACLF, especially the short-term mortality rate of patients with early-stage, early-middle-stage, or type A ACLF.