ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Objective:To explore the impact of the hospital health literacy environment on patients′ postoperative pain self-management behaviors, aiming to provide insights for hospitals to implement the Comprehensive Pain Management Pilot Work Program in hospitals and to promote self-health management among patients with other diseases or symptoms. Methods:From November to December 2023, a convenience sampling method was used to select postoperative patients from three grade A tertiary general hospitals in Zhejiang Province for an on-site questionnaire survey. The Chinese version of brief health literacy screen (BHLS), short-form health literacy environment scale (SF-HLES) and postoperative pain self-management behavior questionnaire (PPSMB) were used as survey tools to investigate the health literacy level of patients, the health literacy environment of the hospital, and the postoperative pain management behaviors of patients. Two-way ANOVA was used to compare the impact of different dimensions of the hospital health literacy environment on postoperative pain management behaviors among patients with different levels of health literacy. Multiple linear regression analysis was used to explore the relationship between the hospital health literacy environment, individual health literacy, and patients′ postoperative pain self-management behaviors, and to discuss the impact of individual health literacy on patients′ postoperative pain self-management behaviors under different hospital health literacy environments.Results:341 valid questionnaires were collected. The average score of the hospitals′ SF-HLES was (73.62±19.54) points. The average score of the patients′ BHLS was (9.65±2.88) points. The average score of the patients′ PPSMB was (25.99±6.35) points. Two-way ANOVA results showed that the interaction between individual health literacy and the clinical dimension ( F=5.463, P=0.020) and structural dimension ( F=6.470, P=0.011) of the hospital health literacy environment had a statistically significant impact on patients′ postoperative pain self-management behaviors, while the interaction with the interpersonal dimension ( F=0, P=0.984) had no statistically significant impact on pain self-management behaviors. Simple effect analysis indicated that only in the high health literacy environment of the clinical and structural dimensions did the difference in pain self-management behaviors between patients with good health literacy and those with limited health literacy had statistical significance ( P<0.001). Multiple linear regression analysis results showed that for each 1-point increase in the patients′ BHLS score, their PPSMB score increased by 3.74 points ( β1=0.832, P<0.001); for each 1-point increase in the hospital′s SF-HLES score, the patients′ PPSMB score could increase by 0.198 points ( β2=0.610, P<0.001). In a low health literacy environment, individual health literacy did not affect pain self-management behaviors ( P>0.05); however, in a high health literacy environment, for each 1-point increase in the patients′ BHLS score, their PPSMB score correspondingly increased by 4.037 points ( β4=0.317, P<0.001). Conclusions:The positive impact of individual health literacy on pain self-management is contingent upon a high-quality hospital health literacy environment. This suggests that optimizing the hospital health literacy environment is a necessary precondition for implementing the relevant content of the Comprehensive Pain Management Pilot Work Program and can provide a reference for promote self-health management among patients with pain and other diseases or symptoms.

Objective·To prepare a serine protease inhibitor(Serpin)derived from Tannerella which is associated with periodontosis,and analyze its specificity in inhibiting target proteases and its structural characteristics.Methods·Through amino acid sequence analysis,a Serpin from the human oral microbiome database(eHOMD)was selected and expressed in Escherichia coli.The recombinant protein was purified using methods such as nickel ion affinity chromatography.Its specificity in inhibiting serine proteases was analyzed,followed by an analysis of its three-dimensional spatial structure using structural biology methods.Results·A novel Serpin,named Tannerpin-M,with methionine as the active center P1 residue,was identified,and a high-purity recombinant protein was successfully prepared from Escherichia coli BL21(DE3).Further activity testing demonstrated that recombinant Tannerpin-M could effectively form SDS-stable covalent complexes with proteases derived from granulocytes(human neutrophil elastase,cathepsin G,and proteinase 3),as well as with other proteases including kallikrein 1(KLK1),KLK7,and elastase.Tannerpin-M inhibited KLK7 with a second-order association rate constant of 4.12×104 L/(mol·s).The crystal structure of Tannerpin-M in its relaxed state conformation was resolved at a resolution of 2.4 ?(1 ?=0.1 nm).It revealed that Tannerpin-M possessed a significantly elongated reactive center loop and could undergo the classical conformational transition from a stressed to a relaxed state.Conclusion·Tannerpin-M,derived from oral pathogenic bacteria,is a typical inhibitory Serpin,and can effectively inhibit the serine protease released by granulocytes,by which it may protect the oral pathogenic bacteria from attacks of the human immune system.

Objective·To prepare a serine protease inhibitor(Serpin)derived from Tannerella which is associated with periodontosis,and analyze its specificity in inhibiting target proteases and its structural characteristics.Methods·Through amino acid sequence analysis,a Serpin from the human oral microbiome database(eHOMD)was selected and expressed in Escherichia coli.The recombinant protein was purified using methods such as nickel ion affinity chromatography.Its specificity in inhibiting serine proteases was analyzed,followed by an analysis of its three-dimensional spatial structure using structural biology methods.Results·A novel Serpin,named Tannerpin-M,with methionine as the active center P1 residue,was identified,and a high-purity recombinant protein was successfully prepared from Escherichia coli BL21(DE3).Further activity testing demonstrated that recombinant Tannerpin-M could effectively form SDS-stable covalent complexes with proteases derived from granulocytes(human neutrophil elastase,cathepsin G,and proteinase 3),as well as with other proteases including kallikrein 1(KLK1),KLK7,and elastase.Tannerpin-M inhibited KLK7 with a second-order association rate constant of 4.12×104 L/(mol·s).The crystal structure of Tannerpin-M in its relaxed state conformation was resolved at a resolution of 2.4 ?(1 ?=0.1 nm).It revealed that Tannerpin-M possessed a significantly elongated reactive center loop and could undergo the classical conformational transition from a stressed to a relaxed state.Conclusion·Tannerpin-M,derived from oral pathogenic bacteria,is a typical inhibitory Serpin,and can effectively inhibit the serine protease released by granulocytes,by which it may protect the oral pathogenic bacteria from attacks of the human immune system.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.