OBJECTIVE To comprehensively evaluate the 16 commonly used kinds of enteral nutrition preparations in Hebei province， aiming to provide a reference for the selection of drugs in medical institutions and clinical drug decision-making. METHODS Based on the Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions （the Second Edition）， evaluation evidence was collected， and the included drugs were scored and evaluated from four dimensions of pharmaceutical characteristics， clinical characteristics， economy and other attributes. RESULTS & CONCLUSIONS The scores for Enteral nutritional emulsion （TPF-T）， Enteral nutritional emulsion （TPF-D）， Enteral nutritional emulsion （TPF）， Enteral nutritional emulsion （TPF-HE）， Enteral nutritional emulsion （TP）， Enteral nutritional emulsion （SP）， Enteral nutritional suspension （TPF） （1.5 kcal/mL， 1 kcal＝4.184 kJ）， Enteral nutritional suspension （TPF） （1.0 kcal/mL）， Intact protein enteral nutrition （powder）， Enteral nutritional suspension （TPF-DM）， Enteral nutritional suspension （TPF-MCT）， Enteral nutritional suspension （SP）， Short- peptide enteral nutrition， Enteral nutritional powder （TP）， Enteral nutritional suspension （TPF-D） and Enteral nutritional suspension （TPF-FOS） were 82.9， 84.1， 84.1， 86.1， 78.4， 79.1， 82.6， 82.3， 82.4， 80.2， 83.0， 82.4， 82.1， 85.7， 76.0， 82.4 points， respectively. All medications scored above 70 points. In practice， appropriate drugs can be selected according to clinical requirements and patient needs.

OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

OBJECTIVE To study the role of phosphatidylinositol-3-kinase （PI3K） on sunitinib-induced myocardial systolic dysfunction. METHODS Using human-induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMS） as objects， the contractile force of cardiomyocytes was measured by CardioExcyte 96 system， and IC50 of sunitinib was calculated after hiPSC- CMS were treated with sunitinib at different concentrations [0 （control）， 0.5， 1， 3， 5， 10 μmol/L] for 24 hours. The effects of sunitinib （3.14 μmol/L） on the contractile frequency of cardiomyocytes， calcium transient amplitude and calcium transient recovery time course， mRNA expression of myocardial injury markers atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP） and β-myosin heavy chain （β-MHC） were detected. PI3K activator 3，4，5-triphosphate phos-phatidylinositol （PIP3， 1 μmol/L） and sunitinib were used to intervene in hiPSC-CMs jointly， so as to investigate the role of PI3K in the myocardial systolic dysfunction induced by sunitinib. RESULTS Sunitinib inhibited the contractile force of hiPSC-CMs in a concentration-dependent manner. IC50 of sunitinib was 3.14 μmol/L. After intervention with 3.14 μmol/L sunitinib， the contractile frequency of hiPSC-CMs and calcium transient amplitude were decreased significantly （P＜0.05 or P＜0.01）； the duration of calcium transient recovery was prolonged significantly （P＜0.05）， and mRNA expressions of ANP， BNP and β-MHC were significantly increased （P＜0.01）. After PI3K was activated with PIP3， the contractile force of hiPSC-CMs was increased significantly （P＜0.01）. CONCLUSIONS Activating PI3K activity is a potential molecular mechanism to improve myocardial toxicity induced by sunitinib.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

Objective To introduce the construction of clinical research information system of a tertiary grade A comprehensive hospital in Shanghai.Methods Based on the database construction,the structured inpatient medical records,surgical records and ancillary diagnostic report are designed and the application terminal is developed.Results A full-link normalized clinical research information system for research-based cases covering all aspects of clinical research is developed,which can provide customized and structured data.Conclusions The clinical research information system provides convenience for clinical medical research,and its practice has certain reference significance.

This paper introduced the design and application of the performance appraisal scheme for the interventional operation platform.The comparison of interventional operations before and after the means of performance management in place, presented the effective role of performance management in interventional operation platform, and analyzed the motivation effect of performance management on the enthusiasm of interventional operators.The authors recommend performance appraisal and incentive compensation mechanism to motivate the clinical use of the platform, and greater application of such a common platform, for perfection of surgery performance management.

Objective To analyze the effects of quality supervision and continuous improvement system on optimizing in-hospital diagnosis and treatment process in patients with acute ischemic stroke (AIS).Methods From September 2013 to May 2016,424 consecutive patients with AIS treated with intravenous thrombolysis and/or endovascular therapy in Changhai Hospital,the Second Military Medical University were enrolled retrospectively.They were analyzed according to the annual running process (the first year[from September 2013 to August 2014],the second year[from September 2014 to August 2015],and the third year[from September 2015 to May 2016]).The spend time and delay (DTN>60 min,DTP>90 min) rate of each treatment process in the first,second,and third year (time from door-to-imaging[DTI],door-to-needle[DTN],imaging-to-needle (ITN),door-to-groin puncture (DTP) and imaging-to-groin puncture (ITP) were compared.Taking the time periods (>median) of having significant differences of the spend time of the treatment processes as the dependent variables in the first,second,and third year,the influence of the years and treatment modalities on delay was observed.The difference of constituent ratio of the reasons for delay in intravenous thrombolysis and endovascular therapy (objective reasons/other reasons) in different years were analyzed.Results (1) DTIs were 23.0 (11.0,42.0) min,22.0 (10.1,39.0) min,and 13.0 (6.0,27.0) min,respectively,and DTNs were 50.0 (30.0,77.1) min,45.0 (30.0,70.2) min,and 36.0 (24.0,57.0) min,respectively in the first,second,and third year.The spending time was shortened year by year.There were significant differences among the different years (all P<0.01).The spending time of DTP had a tendency to be shortened,but there were significant differences among different years (P=0.06).There were no significant differences between the spending time of ITN and ITP (all P>0.05).(2) The DTN delay rates were 33.3% (40/120),20.7% (29/140),and 8.1% (9/111),respectively in the first,second,and third year.There were significant differences among the 3 years (x2=22.111,P<0.01).There were no significant differences among the DTP delay rates (P=0.08).(3) Multivariate Logistic regression analysis showed that taking the first years as a reference,the risk of DTI delay was reduced in the third year (OR,0.174,95%CI 0.101-0.298,P<0.01),the risks of DTN delay were reduced in the second and third year (OR,0.564,95%CI 0.338-0.941;OR,0.180,95%CI 0.101-0.320,all P<0.05).For simple intravenous thrombolysis,bridging therapy was a protective factor for the improvement of treatment efficiency in the DTI process (OR,0.530,95%CI 0.297-0.943,P=0.031).Compared with the bridging therapy,the direct endovascular therapy was a protective factor for DTP treatment (OR,0.427,95%CI 0.202-0.901,P=0.025).The remaining independent variables were not associated with the occurrence of DTN and DTP delay (all P>0.05).(4) During the three years,the delay of intravenous thrombolysis was mainly due to objective reasons.The constituent ratio of other reasons caused delay of intravenous thrombolysis was decreased year by year.There was no other reasons for delay in the third year).There was no significant difference in the constituent ratio of the delay reasons in endovascular treatment (x2=3.622,P=0.164).Conclusion Under the existing process and resource allocation,setting the DTN target time and implementing continuous quality improvement are conducive to the effective implementation of brain CT scan and continuous optimization of intravenous thrombolysis in the processes in AIS patients with the first diagnosis.

BACKGROUND: A large number of experiments in vivo and in vitro have shown that mesenchymal stem cells may obviously inhibit the lymphocytes and other immunocytes.OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cell transplantation on the immune function and prognosis of patients suffering decompensated liver cirrhosisn due to hepatitis B.METHODS: 118 patients with decompensated cirrhosis due to hepatitis B were randomly divided into control group (n=59) and observation group (n=59). The two groups all received normal medical treatment, and in addition, the observation group also received human umbilical cord mesenchymal stem cell transplantation. (4.0-4.5)×108 stem cells were transplanted twice by intervention via proper hepatic artery (10 mL) and intravenous infusion (10 mL) within 1 week after admission. The levels of serum interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β and the percentage of lymphocyte subsets in the peripheral blood were determined in the two groups before and 1, 4 weeks after treatment. The model for end-stage liver disease (MELD) score and Child-Pugh score of 118 patients after treatment for 12 weeks were observed and recorded, and liver failure, complications and survival during follow-up period in the two groups were observed. RESULTS AND CONCLUSION: After treatment for 1 and 4 weeks, the levels of serum interleukin-6 and tumor necrosis factor-α in the observation group were significantly lower than those in the control group (P < 0.05 or P <0.001), but the levels of serum interleukin-10 and transforming growth factor-β in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001). After treatment for 1 week, the percentagesof CD3+CD4+T cell and CD4+CD25+Treg cells in the observation group were significantly higher than those in the control group (P < 0.001), but the percentages of CD3+CD8+ T cells and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 4 weeks, the percentages of CD3+ T cell ,CD3+CD4+ T cells and CD4+CD25+ Treg cells in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001), but the percentages of CD3+CD8+ T cell and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 12 weeks, the MELD and Child-Pugh scores in the observation group were significantly lower than those in the control group (P < 0.05).During the follow-up period, none of the cases in the observation group developed liver failure, but five cases in the control group did. In addition, the incidence of complications and cumulative mortality in the observation group were significantly lower than those in the control group (P < 0.05). These results show that the human umbilical cord mesenchymal stem cell transplantation may alleviate liver inflammation and improve liver function, and then may reduce the incidence of hepatic failure and mortality for patients with decompensated cirrhosis due to hepatitis B.