ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

Financial incentives， as an intervention in behavioral therapy， have been proven to be beneficial in many health behaviors， such as drug addiction treatment， long-term antiviral therapy， and the prevention and treatment of chronic diseases. At present， typical financial incentive schemes mainly include commitment contracts and lottery-based models. Key factors in the design of such interventions include the adaptability of behavioral economic principles and medication behavior， the effectiveness and cost-effectiveness of design scheme， and the acceptability of intervention population. Although financial incentives have accumulated rich experience in health behavior interventions abroad， research on medication adherence remains limited， with existing intervention scheme design and mechanism constraints， and their effectiveness potentially varying across different cultural and social environments. China should explore practical models of financial incentives to enhance medication adherence, considering patients’ medication patterns and socio-cultural factors.

Medication adherence is an important indicator for assessing whether patients follow medical advice during treatment， and its level directly affects disease control and the quality of life of patients. Therefore， accurate and effective assessment is essential for chronic disease management and intervention. This paper takes chronic obstructive pulmonary disease （COPD） and asthma， two types of chronic respiratory diseases， as representative to review the existing measurement methods and current application status of medication adherence. It is found that the existing assessment methods for medication adherence can be categorized into objective measurement methods and subjective measurement methods. Objective measures include drug concentration monitoring， pill counting， and electronic medication devices， which generally offer high accuracy. Subjective measures include physician assessments， inhalation technique evaluations， and questionnaires. While these methods are straightforward and easy to implement， their accuracy is often influenced by the subjective factors of assessors of patients， which may lead to biased results. Currently， there is still a lack of a universally accepted “gold standard” for evaluating medication adherence. Selecting the appropriate measurement method requires a comprehensive consideration of factors such as research objectives， disease type， patient characteristics， and data availability to ensure the validity and reliability of the assessment results.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

OBJECTIVE To explore the effects of Yueju Pill on depression and gastrointestinal function in depressed co-morbid functional dyspepsia mice.METHODS C57BL/6J mice were randomly divided into control group,model group,Yueju Pill low-dose group,Yueju Pill high-dose group and positive drug group.A co-morbidity model was constructed using chronic unpredictable mild stress(CUMS),and the mice were assessed for depression-like behaviour and neuronal damage by behavioural tests and Nissl staining;gastrointestinal function was assessed by HE staining of gastric and intestinal tissues,gastric emptying rate,and small intestinal propul-sive rate;PACAP,VIP,IL-6,TNF-α,and BDNF expression were detected by ELISA;PAC1-R,Vipr1,and Vipr2 protein expres-sion were detected by protein immunoblotting.RESULTS Mice in the model group showed depression-like behaviour,reduced num-ber of hippocampal nidus,slowed gastrointestinal motility,elevated serum inflammatory factors IL-6 and TNF-α(P＜0.05,P＜0.01),and reduced expression of PACAP,VIP,and BDNF(P＜0.05,P＜0.01),The PAC1-R,VPAC1-R,VPAC2-R expression de-creased in the hippocampus and gastric sinus,duodenal tissue(P＜0.05,P＜0.01).Compared with the model group,the low and high dose groups of Yueju Pill improved the above indexes except for Vipr1 and Vipr2(P＜0.05,P＜0.01).CONCLUSION Yueju Pill can reduce inflammatory factors through PACAP/PAC1-R,increase the level of BDNF,and improve the depression-like behaviour and gastrointestinal dysfunction in CUMS mice.

ObjectiveTo explore the association between triglyceride-glucose （TyG） index and major adverse cardiovascular events （MACEs） risk in coronary heart disease （CHD） patients with blood stasis syndrome after percutaneous coronary intervention （PCI）. MethodsA total of 857 CHD patients with blood stasis syndrome after PCI were enrolled and divided into four groups according to the baseline TyG index quartiles， Q1 （TyG ＜ 8.51）， Q2 （8.51 ≤ TyG ＜ 8.88）， Q3 （8.88 ≤ TyG ＜ 9.22）， and Q4 （TyG ≥ 9.22）. The clinical outcome was defined as a compound endpoint of cardiovascular events including cardiac death， non-fatal myocardial infarction， unplanned revascularization， in-stent restenosis and stroke. The machine learning Boruta algorithm was used for feature selection related to MACEs risk. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to compare the differences in MACEs risk among the four groups. Restricted cubic spline （RCS） and subgroup analysis were performed to determine the relationship between the TyG index and MACEs risk. The area under the receiver operating characteristic （ROC） curve （AUC）， calibration curve and Hosmer-Lemeshow test， and decision curve analysis （DCA） were plotted to evaluate the predictive value of the TyG index for MACEs risk. ResultsThe median follow-up time of the included patients was 2.45 years. During the follow-up period， 313 cases （36.52%） of new MACEs occurred. The incidence of MACEs in Q1， Q2， Q3， Q4 group was 28.17% （60/213）， 29.05% （61/210）， 39.45% （86/218） and 49.07% （106/216）， respectively. Kaplan-Meier survival analysis suggested statistically significant differences in MACEs risk among the four groups （P＜0.001）. Cox proportional hazards regression model analysis found that the risk of MACEs in patients with high TyG index increased by 60.1% （P＜0.01）. Using Q1 as the reference， the MACEs risk in Q2， Q3 and Q4 groups gradually increased， and the trend was statistically significant （P＜0.05）. RCS model suggested that the TyG index was nonlinearly associated with the MACEs risk （P＜0.001）. The TyG index had a good predictive performance for MACEs risk according to ROC analysis （AUC=0.758， 0.724-0.792） and Hosmer-Lemeshow test （χ² = 4.319， P = 0.827）. Additionally， DCA analysis also suggested a good clinical efficacy of the TyG index for predicting MACEs. Subgroup analysis showed that different baseline TyG index was positively correlated with the MACEs risk in the stratification of age， male， BMI， history of diabetes and hypertension， and low-density lipoprotein cholesterol （LDL-C）≥1.8 mmol·L^-1（P＜0.05）. ConclusionThe elevated TyG index is closely corrected with an increased risk of MACEs in CHD patients with blood stasis syndrome after PCI， indicating a guiding significance for early risk stratification and clinical decisions.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.