OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury. After injury, Schwann cells produce an inflammatory response and secrete various chemokines, inflammatory factors, and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages, enhancing their phagocytotic ability, and thus play an important role in promoting nerve regeneration. Macrophages have also been found to promote vascular regeneration after injury, promote the migration and proliferation of Schwann cells along blood vessels, and facilitate myelination and axon regeneration. Therefore, there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration, but this has not been systematically summarized. In this review, the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other, to provide directions for research on accelerating nerve injury repair.
Schwann Cells/metabolism* ; Peripheral Nerve Injuries/physiopathology* ; Animals ; Macrophages/immunology* ; Nerve Regeneration/physiology* ; Humans ; Cell Movement/physiology*

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective:Analyzing the epidemic trends and spatio-temporal distribution characteristics of condyloma acuminatum in China from 2018 to 2023.Methods:Data of condyloma acuminatum cases and incidence rate including 31 provinces (autonomous regions and municipalities) from 2018 to 2023 were collected through the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Incidence trend analysis was conducted using Joinpoint 4.9.1 software, and spatial autocorrelation analysis using ArcGIS 10.5 software. Spatio-temporal scanning analysis was carried out with SaTScan 10.1.2 software.Results:The incidence rate of condyloma acuminatum declined from 7.26 per 100 000 in 2018 to 7.19 per 100 000 in 2023. The average annual percent change was -0.26%, which was no statistically significant downward trend ( t=-0.26, P=0.806). A significant positive global spatial autocorrelation was observed in the county-level incidence rate across the country, with the global Moran's I ranging from 0.55 to 0.60 (all P<0.001); the Getis-Ord General test statistic Z( G) was all >1.96, indicating a high-value clustering pattern in the reported incidence rate of condyloma acuminatum. The local spatial autocorrelation analysis detected 256, 244, 246, 284, 308, and 315 hotspots each year, which were mainly located in the provinces of Zhejiang, Fujian, Guangdong, Guizhou, Yunnan and Chongqing. Spatio-temporal scanning analyses identified 76 statistically significant spatiotemporal clusters covering 25 provinces (autonomous regions and municipalities). Conclusions:From 2018 to 2023, the reported incidence rate of condyloma acuminata in China exhibited a mild decline. The distribution of hotspot areas and spatiotemporal clusters was largely consistent, primarily in the southeastern coastal and southwestern regions.

OBJECTIVE To explore the pharmacodynamic related substances and mechanism of Weining San(WNS) against gastric ulcer(GU) according to fingerprint and network pharmacology. METHODS Twelve batches of WNS fingerprints were established by HPLC, and methodological investigation was carried out. Combined with reference substances, characteristic peaks were identified, pharmacodynamic related substances were screened, and network pharmacological analysis was carried out. Using TCMIP and Swiss Target Prediction database to retrieve component targets; Using OMIM, GeneCards and Drugbank databases to retrieve GU disease targets, taking the intersection targets of components and diseases, using String database to construct protein-protein interaction network diagram, and analyzing topological parameters; Using Cytoscape 3.8.2 software to construct "component-disease-target" network diagram; GO and KEGG enrichment analysis of intersection targets were carried out by Metascape website. Then the alcoholic GU mouse model was established by intragastric administration of absolute ethanol to verify the results of network pharmacology prediction. RESUITS　The precision, stability and repeatability of HPLC fingerprint method were good. By comparison and comprehensive analysis of control substances, notoginsenoside R1, ginsenoside Rg1, militarine, ginsenoside Rb1, schisandrin, schisandrol B, deoxyschizandrin and schisantherin A were identified as pharmacodynamic related substances in WNS, which may play their role by regulating core targets such as AKT1, IL-6, STAT3, TNF, IL1B and key signal pathways such as PI3K-Akt and JAK-STAT. The gastric ulcer index, ulcer inhibition rate and HE staining showed that WNS could improve gastric mucosal injury in GU mice. The results of ELISA, WST-1 and TBA showed that WNS could decrease the levels of TNF-α, IL-6, IL-1β and MDA, and increase the levels of SOD and PGE2, suggesting that the anti-GU effect of WNS was related to the inhibition of inflammatory reaction and oxidative stress mechanism, which further verified the prediction of network pharmacology. CONCLUSION This study combines fingerprint analysis, network pharmacology, and animal experimental validation to explore the pharmacodynamic related substances and mechanisms of WNS anti-GU efficacy, providing reference for quality control and clinical research of WNS.

Objective We systematically analyze the changes in the count and function of platelet at the early sepsis based on clinical study and single cell sequencing.Methods Clinical data of sepsis patients at the early stage were collected and had been compared between different prognostic groups in the prospective case-control study.The independent risk factors of death were analyzed by logistic regression,and the predictive efficacy of clini-cal indicators was evaluated by receiver operating characteristic(ROC)curve.The healthy volunteers and sepsis patients were recruited.Clinical researchers collected peripheral venous blood samples for sorting cell samples to carry out single-cell RNA sequencing(sc-RNA seq).Through bioinformatics techniques,we analyzed the changes in platelet count,the significantly differential-expressed genes and its enriched functional signaling pathways in the early stages of sepsis.Results(1)A total of 224 patients were enrolled,with a 90 day survival rate of 70.5%.Compared with the survival group,the count of platelet and MAP in the death group at the early stage of sepsis were significantly lower,but the plasma lactate content and SOFA score were significantly higher.(2)Based on single cell sequencing technology,cells are annotated as six groups.The proportion of innate immune cells(neutrophils,monocytes,and dendritic cells)was significantly increased in the early stage of sepsis compared to the healthy volun-teers(2.15∶1),while platelets significantly decreased(0.31∶1).(3)Through bioinformatics technology,CD41/CD42a/CD61 was identified as platelet specific molecules,with significantly increased expression levels in sepsis.Three molecules can distinguish platelets together.(4)771 genes were significantly upregulated and 1101 genes were significantly downregulated in platelets of patients with sepsis,including core molecules involved in physiological functions such as cell adhesion,chemotaxis,and immune response.Functional analysis suggests that differentially expressed genes are enriched in coagulation,immune functions and cell death,participating in oxidative phosphory-lation,leukocyte chemotaxis,iron death,and NOD like receptor signaling pathways.Conclusion Reduced platelet count is associated with poor prognosis in the early stage of sepsis.The specific high expression molecules CD41/CD42a/CD61 that are significantly upregulated in platelets can serve as biomarkers for platelets.Platelets not only mediate cell adhesion and coagulation cascade,but also participate in functional changes such as immune cell chemotaxis,inflammatory response,and the pathological death of inflammatory cells.

There are mutual neural projections between the ventral tegmental area(VTA)and the me-dial prefrontal cortex(mPFC),which form a circuit.Recent studies have shown that this circuit is vital in regu-lating arousal from sleep and general anesthesia.This paper introduces the anatomical structures of VTA and mPFC and the roles of various neurons and projection pathways in the regulation of arousal,aiming to provide new ideas for further research on the mechanism of arousal from sleep and general anesthesia.

Objective:To explore rehabilitation effect of hyperbaric oxygen chamber treatment on patients with sequelae of brain injury.Methods:From January 2023 to January 2024,a total of 80 patients with sequelae of brain injury were selected from The First Affiliated Hospital of Xinjiang Medical University,and they were randomly divided into control group and observation group,with 40 patients in each group.The control group received conventional treatment and intervention,while the observation group was treated with hyperbaric oxygen chamber on the basis of the conventional treatment and intervention of control group.The levels of serum oxidative stress indicators,neurotrophic factor indicator,as well as neurological function,cognitive function,motor function and quality of life of the two groups were evaluated.Results:After treatment,the levels of serum oxidative stress indicators such as neutrophil gelatinase-related lipocalin(NGAL),matrix metalloproteinase-9(MMP-9),reactive oxygen species(ROS)of observation group were significantly higher than those of control group(t=5.578,11.065,3.706,P<0.05),respectively,and the ubiquitin carboxy-terminal hydrolase L1(UCH-L1)of neurotrophic factor,neuron-specific enolase(NSE)and serum calcium-binding protein(S100-β)of observation group were significantly lower than those of control group,while cerebral extraction rate of oxygen(CERO2)of serum oxidative stress indicators of observation group was significant higher than that of control group,and the differences of them were significantly(t=5.170,4.277,4.130,2.260,P<0.05),respectively.After treatment,the score of National Institutes of Health Stroke Scale(NIHSS)of observation group was lower than that of control group,and the score of Mini-Mental State Examination(MMSE)of observation group was significantly higher than that of control group,and the differences of them were statistical significance(t=15.874,7.820,P<0.05),respectively.In additions,the scores of Loewenstein Occupational Therapy Cognitive Assessment(LOTCA),Simplified Fugl-Meyer Assessment(FMA)upper and lower limbs of observation group were significantly higher than those of control group,and the differences of them between two groups were significant(t=14.051,4.766,8.622,P<0.05),respectively.The scores of physiological,psychological,social and environment factor of World Health Oganization Quality of Life Scale(WHOQOL-BREF)in observation group were higher than those in control group,and the differences of them between two groups were statistically significant(t=19.968,21.979,18.077,19.695,P<0.05).Conclusion:The application of hyperbaric oxygen chamber in patients with sequelae of brain injury is beneficial to adjust the levels of serum oxidative stress indicator and neurotrophic factor indicator,which can improve the deficit of neurological function,and promote the recovery of cognitive and motor functions,and improve the quality of life.