OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

Objective : To explore the risk factors of prognosis in patients with severe community-acquired pneumonia(SCAP) in different age groups. Methods : A multi-center and prospective study was conducted at 11 teaching hospitals in China from December 2017 to October 2021. Patients who met the criteria were assigned to the elderly group(≥65 years) and the non-elderly group(18-64 years) to demonstrate the clinical characteristics of SCAP. Patients were divided into survival group and death group according to whether they died in hospital, to determine the risk factors associated with mortality by multivariate logistic regression analysis. Results: A total of 170 patients with SCAP were included in the study. The age of SCAP was 20-93(65.75±15.23) years old, and the proportion of SCAP in the elderly was 58.82%(100/170). In-hospital mortality of non-elderly SCAP was 24.3%(17/70), and the in-hospital mortality of elderly SCAP was 28%(28/100). Compared with non-elderly group, patients in elderly group had higher severity score and more complications on admission, but the symptoms of fever and respiratory rate at admission were less obvious. In multivariable logistic regression analysis, the factors significantly associated with in-hospital mortality of non-elderly SCAP were pneumonia severity index(PSI) score(P=0.016,OR=1.022, 95%CI1.004-1.041) and invasive mechanical ventilation(P=0.037,OR=4.543, 95%CI1.092-18.898) on admission, and the risk factors associated with in-hospital mortality in elderly SCAP were sequential organ failure assessment(SOFA) score(P=0.006,OR=1.240, 95%CI1.063-1.446) and combined with coronary artery disease on admission(P=0.037,OR=2.834, 95%CI1.066-7.534). Conclusion In-hospital mortality for SCAP is high. PSI score and invasive mechanical ventilation are risk factors for in-hospital mortality of non-elderly patients with SCAP, and SOFA score and combined with coronary artery disease on admission are risk factors for in-hospital mortality of elderly patients with SCAP.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Objective To explore the correlation between the pathogenesis of toxins damaging liver collateral and the incidence of type 2 diabetes mellitus(T2DM)based on the theory of five circuits and six qi.Methods A total of 986 patients with T2DM treated in the Department of Endocrinology and Metabolism at the Affiliated Hospital of Changchun University of Chinese Medicine from February 2019 to October 2023 were selected as the study subjects.The influences of circuit and qi indicators in the theory of five circuits and six qi on the constitutional characteristics of T2DM patients and the role of pathogenesis of toxins damaging liver collateral in the incidence of T2DM were investigated.Results(1)The five-circuit and six-qi analysis showed that the yearly circuit and sitian/zaiquan conditions had no significant effect on the constitutional characteristics of patients with T2DM(P＞0.05).However,dominant circuit,guest circuit,dominant qi and guest qi significantly influenced the constitutional characteristics of patients with T2DM(P＜0.05).For the distribution of circuit-qi indicators at birth among the 986 patients,dominant circuit was predominated by the terminal circuit of taiyang cold-water,guest circuit was characterized by deficient wood circuit or excessive water circuit,dominant qi was predominated by yangming dry-metal,and guest qi was characterized by taiyin damp-earth.(2)The correlation between the pathogenesis of toxins damaging liver collateral and the incidence of T2DM through comparative analysis revealed that the conveying and dispersing function of the liver plays a leading role in maintaining the body's yin-yang balance and ensuring free movement of qi,indicating that the critical role of toxins damaging liver collateral is the key to the incidence of diabetes.Conclusion Circuit-qi indicators have a certain influence on the constitutional characteristics of T2DM patients.The circuit-qi features at birth of the individuals prone to T2DM are as follows:dominant circuit predominated by the terminal circuit of taiyang cold-water,guest circuit characterized by deficient wood circuit or excessive water circuit,dominant qi being yangming dry-metal,and guest qi being taiyin damp-earth.Pathogenesis of toxins damaging liver collateral is closely related to the incidence of T2DM.Therefore,in treatment,the regulatory role of the liver should be emphasized,and liver-soothing herbs should be used based on syndrome differentiation,aiming for holistic treatment of the physique and the spirit and enhancing the therapeutic efficacy.The exploration will provide a new perspective and approach for the treatment of T2DM.

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

AIM:To observe the effect of dexme-detomidine(DEX)on cerebral ischemia and reperfu-sion(I/R)injury and investigate the possible mecha-nism of nuclear factor erythroid derived 2-like 2(Nrf2)mediated ferroptosis on hippocampal neu-rons.METHODS:The oxygen glucose deprivation/reoxygenation(OGD/R)model in rat primary cul-tured hippocampal neurons was simulated,DEX(50 μmol/L)and Nrf inhibitor BRU(100 nmol/L)were used to observe the changes of ROS levels by DHE fluorescence probe.The middle cerebral ar-tery occlusion model in male SD rats were estab-lished,the degree of neurological impairment was detected by Longa score,and cerebral infarct size was detected by TTC staining.The Fe2+concentra-tion and levels of oxidative stress related factors were detected,oxidative stress and ferroptosis re-lated protein expressions were detected by West-ern blot.RESULTS:The fluorescence intensity of DHE in OGD/R+Dex Group was lower than that in CON group,and the fluorescence intensity of DHE in OGD/R+DEX+BRU group was higher than that in OGD/R+Dex group.Compared with Sham group,the Longa score and cerebral infarct size in I/R group were significantly increased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were significantly decreased.MDA and Fe2+concentrations were in-creased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were decreased,and TFR1 protein expression was increased.Compared with I/R group,in DEX+I/R group,the Longa score and ce-rebral infarct size were decreased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were increased.MDA and Fe2+concentrations were decreased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were increased,and TFR1 protein expression was decreased.The Nrf2 inhibitor Bru reversed the role of DEX.CONCLUSION:DEX protects against ce-rebral I/R injury through activating Nrf2 signaling pathway and inhibiting ferroptosis in hippocampal neurons.

The treatment of multidrug-resistant gram-negative bacterial infections has become a challenge in today's healthcare field,and time-to-event data analysis has shown significant value in clinical prognostic studies of critically ill patients.This study comprehensively reviewed the results of the application of time-to-event analysis in clinical studies of anti-multidrug-resistant gram-negative bacterial drugs,aiming to provide a scientific basis for the optimization of therapeutic strategies and prognostic assessment of multidrug-resistant gram-negative bacterial infections,and to promote the widespread application of time-to-event analysis methods in similar studies.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

Zika virus(ZIKV),a flavivirus transmitted primarily through the bites of Aedes mosquitoes,led to a major public health crisis in the 2015 Brazilian outbreak.The World Health Organization(WHO)subsequently designated the Brazilian ZIKV epi-demic as a Public Health Emergency of International Concern(PHEIC)in 2016,because of its devastating consequences.Congenital Zika syndrome(CZS),a distinctive constellation of teratogenic effects caused by intrauterine ZIKV infection,is characterized by mi-crocephaly,ocular lesions,cortical calcifications,congenital contractures,and multisystem developmental anomalies.CZS poses sub-stantial risks to neonatal survival and long-term health outcomes.Despite containment efforts,ZIKV remains prevalent across multiple endemic regions,thus underscoring persistent threats to maternal-fetal health.Systematic longitudinal monitoring of CZS cohorts,inte-grated with interdisciplinary approaches bridging clinical assessments and mechanistic studies,is imperative to elucidate the pathogen-esis and advance therapeutic strategies.To inform future investigations and identify novel research directions in CZS pathobiology,this review synthesizes recent advances in three key domains:clinical characterization of CZS manifestations,development of CZS animal models,and breakthroughs in molecular mechanisms underlying ZIKV-induced teratogenesis.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.