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 To investigate the relationship between serum orexin-A(OXA)and aspartate amin-otransferase(AST)levels and the disease severity and prognosis in patients with acute ischemic stroke(AIS).Methods A total of 167 AIS patients(AIS group)treated at Hebei Provincial People's Hospital from January 2021 to January 2024 and 84 healthy individuals undergoing physical examinations(control group)were selected as the research objects.AIS patients were categorized by severity into mild AIS group[National Institutes of Health Stroke Scale(NIHSS)score＜5,42 cases],moderate AIS group(NIHSS score 5—＜16,56 cases),moderate-to-severe AIS group(NIHSS score 16—＜21,36 cases),and severe AIS group(NIHSS score ≥21,33 cases).Based on 3-month prognosis(modified Rankin scale),patients were divided into poor prognosis group(＞2 grade,54 cases)and good prognosis group(≤2 grade,113 cases).Spearman correlation analysis was used to assess the relationship between NIHSS scores and serum OXA and AST levels in AIS pa-tients.Multivariate unconditional Logistic regression was used to determine the relationship between serum OXA and AST levels and the prognosis of AIS patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of serum OXA and AST levels for prognosis.Results Compared with the control group,serum OXA level in the AIS group was lower,while AST level was higher(P＜0.05).Ser-um OXA level progressively decreased,and AST level progressively increased across the mild,moderate,mod-erately severe,and severe AIS groups(P＜0.05).NIHSS score was negatively correlated with serum OXA level and positively correlated with AST level in AIS patients(P＜0.05).High OXA level was an independent protective factor for poor prognosis in AIS patients,while high AST level was an independent risk factor(P＜0.05).The area under the curve(AUC)of the combined assessment of serum OXA and AST levels in predic-ting poor prognosis in AIS patients was 0.873,which was greater than the AUC of OXA(0.793)and AST(0.770)alone(P＜0.05).Conclusion In AIS patients,lower serum OXA level and higher AST level are as-sociated with disease severity and poor prognosis.The combined evaluation of serum OXA and AST levels has higher predictive value for AIS prognosis.

Objective To observe the clinical efficacy of mind-regulating and meridians-dredging acupuncture combined with rehabilitation training in treating limb dysfunction in recovery period of cerebral infarction(CI).Methods A total of 110 cases of patients with limb dysfunction in recovery period of CI were randomly divided into observation group and control group,55 cases in each group,the control group was given routine rehabilitation training,and the observation group was treated with mind-regulating and meridians-dredging acupuncture on the basis of intervention of the control group,the course of treatment covered two consecutive weeks.After two weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of scores of traditional Chinese medicine(TCM)syndrome,Fugl-Meyer Assessment(FMA),Berg Balance Scale(BBS)and Modified Barthel Index(MBI)before and after treatment of patients in the two groups were observed.The changes of electromyographic signal before and after treatment were compared between the two groups.And the safety and the occurrence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate was 98.18%(54/55)in the observation group and 87.27%(48/55)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(3)After treatment,the FMA scores of patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the BBS scores and MBI scores of the patients in the two groups improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the root mean square value(RMS)of biceps brachii muscle elbow flexion and triceps brachii muscle elbow extention of the two groups of patients improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(6)During the treatment,there were no obvious adverse reactions occurred in both groups.Conclusion Mind-regulating and meridians-dredging acupuncture combined with rehabilitation training in treating limb dysfunction in recovery period of CI can significantly improve the motor ability of patients,and adjust the electromyographic signals of the affected limbs,with high safety.

Objective To investigate the correlations of serum levels of platelet activation com-plex-1(PAC-1)and soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)with neu-rological deficit and clinical prognosis in patients with acute cerebral infarction(ACI).Methods A total of 170 ACI patients(ACI group)and 85 healthy volunteers(control group)were enrolled in this study.Based on severity of neurological deficit assessed by the National Institutes of Health Stroke Scale(NIHSS)score,ACI patients were divided into of mild neurological deficit group(43 cases),moderate neurological deficit group(57 cases),moderate-to-severe neurological deficit group(37 cases),and severe neurological deficit group(33 cases).Additionally,based on the 6-month fol-low-up prognosis,ACI patients were divided into 51 cases of poor prognosis group and 119 cases of good prognosis group.Enzyme-linked immunosorbent assay was used to measure serum levels of PAC-1 and sTWEAK.Spearman correlation analysis was performed to evaluate their correlations with NIHSS scores in ACI patients.Multivariate unconditional Logistic regression analysis was conducted to determine their relationships with clinical prognosis.Receiver operating characteristic curves were used to explore their evaluation efficacy for poor clinical prognosis.Results Serum levels of PAC-1 and sTWEAK were significantly higher in the ACI group than in the control group(P＜0.05).Ser-um levels of PAC-1 and sTWEAK increased sequentially in the mild,moderate,moderate-to-severe,and severe neurological deficit groups(P＜0.05).Spearman correlation analysis showed that serum levels of PAC-1 and sTWEAK were positively correlated with NIHSS scores in ACI patients(rs=0.715 and 0.706,respectively;P＜0.001).Multivariate unconditional Logistic regression analysis revealed that older age,higher NIHSS score,larger infarct volume,higher PAC-1 level,and higher sTWEAK level were independent risk factors for poor prognosis in ACI patients(P＜0.05).The ar-ea under the curve for the combined assessment of serum PAC-1 and sTWEAK levels for poor clini-cal prognosis in ACI patients was 0.895,which was greater than the areas under the curve for the individual assessments(0.792 and 0.786,respectively;P＜0.05).Conclusion Elevated serum levels of PAC-1 and sTWEAK are closely related to increased neurological deficit and poor clinical prognosis in ACI patients.The combined detection of these two markers has high evaluation efficacy for clinical prognosis in ACI patients.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Refractory chronic cough belongs to the category of "refractory cough" in traditional Chinese medicine， and it is believed that the root cause of intractable chronic cough is wind lodging in the spleen collaterals， with poor spleen yang and deficient kidney essence as the pathologic basis of the disease， which is present throughout the disease. The method advocated is to search the spleen collaterals and eliminate latent wind， warm the spleen yang and smooth the middle jiao， cultivate the kidney essence and consolidate the root， prescribed with modified Fuzi Lizhong Decoction （附子理中汤） plus Erxian Decoction （二仙汤） as the basis. The Fuzi Lizhong Decoction can warm yang and fortify the middle， and smooth the middle jiao， and the Erxian Decoction can cultivate the kidney essence and consolidate the innate. The two prescriptions could combine with Suye （Perilla frutescens）， Jingjie （Dysphania ambrosioides）， Fangfeng （Carum carvi） and other medicinals of cleaning characteristic， or combine with Gouteng （Uncaria rhynchophylla）， Chuanshanlong （Dioscorea nipponica）， Dilong （Kummerowia striata） and other medicinals of worm or cane category， to find the wind and expel pathogen， smooth spleen collaterals.