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.

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 provide a reference for optimizing and promoting the quality standards of Shechuan naolitong granules. METHODS Fifteen batches of Shechuan naolitong granules were used as samples to establish HPLC fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Similarity evaluation and common peak identification were performed， and orthogonal partial least squares discriminant analysis （OPLS-DA） was used to assess quality differences among different batches and to screen quality differential components. Using salvianolic acid B（SAB） as the internal reference， quantitative analysis of multi-components by single-marker （QAMS） was developed to simultaneously determine geniposidic acid （GA）， chlorogenic acid （CA）， vaccarin （VA）， ferulic acid （FA） and senkyunolide I （SI）. The results were compared with those obtained by the external standard method. RESULTS A total of 13 common peaks were identified in the HPLC fingerprints of 15 batches of samples， and the similarities of the spectra were all above 0.96. Seven chromatographic peaks were identified as GA （peak 3）， CA （peak 6）， VA （peak 8）， FA （peak 9）， SI （peak 11）， SAB（peak 12） and TA（peak 13）. OPLS-DA indicated that the differential quality markers among 15 batches were peaks 5， 11 （SI）， and 12 （SAB）.Using SAB as the internal reference， the relative correction factors for GA， CA， VA， FA and SI were calculated as 1.058 4， 0.594 3， 0.643 3， 0.342 7 and 0.262 8， respectively. The mean content of GA， CA， VA， FA， SI and SAB across the 15 batches of samples were 0.155 0， 0.085 4， 0.140 3， 0.071 8， 0.072 7， 1.276 3 mg/g， respectively， showing no significant difference compared with the ESM （P＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS are simple， efficient and economical， providing a reference for the quality control and further development of Shechuan naolitong granules.

Objective In order to understand the current status and influencing factors of perioperative pulmonary rehabilitation knowledge,attitude,and practice among Chinese thoracic surgery nurses,and to provide references for managers to take targeted measures to improve their pulmonary rehabilitation knowledge,attitude,and practice level.Methods From August to October 2023,a convenience sampling method and cross-sectional descriptive survey were used to anonymously survey 1 167 thoracic surgery nurses from tertiary-level A cancer specialty hospitals and tertiary-level A general hospitals in 24 provinces through the Wenjuanxing platform.A general information questionnaire and a knowledge,attitude and practice questionnaire for lung cancer perioperative pulmonary rehabilitation nurses were used,including knowledge dimension(14 items),belief dimension(6 items),and behavior dimension(14 items),totaling 34 items.Univariate analysis and linear regression multivariate analysis were used to determine the influencing factors of the knowledge,attitude and practice level of thoracic surgery nurses in perioperative pulmonary rehabilitation.Results 1 089 nurses completed the investigation.The total standard score and the dimension scores on knowledge,attitude,and behavior of the perioperative pulmonary rehabilitation questionnaire for thoracic surgery nurses were(80.45±11.84)(73.72±14.68)(89.61±11.38)and(83.46±14.48),respectively.The nature of the hospital,whether there is an administrative position,whether the department carries out ERAS,and whether they have received pulmonary rehabilitation training are the influencing factors of the perioperative pulmonary rehabilitation knowledge,attitude,and practice level of thoracic surgery nurses(P＜0.05).Conclusion The knowledge,attitude,and practice of perioperative lung rehabilitation among thoracic surgery nurses are generally at a moderate level.However,their knowledge of perioperative lung rehabilitation is relatively insufficient,and there are many influencing factors.Managers should strengthen pulmonary rehabilitation training for thoracic surgery nurses,improve their knowledge reserves and evidence conversion capabilities,and coordinate cross-integration among multidisciplinary teams to improve their knowledge,attitude and practice in perioperative pulmonary rehabilitation.

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.

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 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.

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions(ADR)of gemcitabine for injection in national centralized volume-based procurement(hereinafter referred to as"centralized procurement"),and provide reference for clinical safe drug use.METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023;basic information of patients,drug use status,patient outcomes,rational drug use and other information were collected,and the occurrence characteristics of ADRs with leukopenia,myelosuppression,neutropenia,thrombocytopenia and liver dysfunction were analyzed.Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender,age,combination of antitumor drugs,original malignant tumor and drug dose with ADR.RESULTS A total of 315 cases reports(315 patients)of gemcitabine-induced ADR were included in this study,with a male-to-female ratio of 1.42∶1 and age of(61.17±9.13)years.The primary malignant tumor was pancreatic cancer(73 cases,23.17%).Leukopenia,myelosuppression and nausea were the most common ADR,followed by neutropenia,thrombocytopenia,liver dysfunction and so on.The severity grade of ADR was mainly 1-2,and the outcome of most ADR was good.Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia(RR=2.154,95%CI:1.218-3.807,P=0.008;RR=3.099,95%CI:1.240-7.744,P=0.016);gender(female)was a risk factor for leukopenia and liver dysfunction(RR=0.508,95%CI:0.302-0.853,P=0.010;RR=0.301,95%CI:0.102-0.887,P=0.029).In terms of drug use rationality,there were 143 cases(45.40%)of drug use in accordance with the indications of the label,and 172 cases(54.60%)of off-label drug use.Among them,the primary malignant tumors were bladder cancer,bile duct cancer and ovarian cancer,which ranked the top three off-label drug use.CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems.The severity of ADRs is mainly classified as 1-2 levels,and most ADRs have good outcomes.Gender(female)and combination medication are risk factors for gemcitabine-induced ADR.Appropriate chemotherapy regimen should be selected according to the patient's condition and physical condition,and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

Objective: Sentinel lymph node biopsy (SLNB) has improved detection of low-volume node metastasis (LVNM) in endometrial cancer (EC), but its prognostic significance and the need for adjuvant therapy (AT) remain unclear. Methods: A comprehensive search was performed until August 31, 2024 in multiple databases and sources. From 21 studies, 65,228 apparent early-stage EC patients were identified: 370 with macrometastases (MAC), 526 with micrometastases (MM), 2,138 with isolated tumor cells (ITCs), and 62,194 with negative nodes. Results: Findings indicated: 1) The MM group had a lower risk of recurrence or progression (R/P) than the MAC group (risk ratio [RR]=0.49; 95% confidence interval [CI]=0.31–0.78;p=0.002), higher risk than the negative nodes group (RR=2.07; 95% CI=1.59–2.68; p<0.001), and similar risk to the ITC group (RR=0.67; 95% CI=0.44–1.02; p=0.060). 2) The MM group had higher 3-year progression-free survival (PFS) (RR=1.36; 95% CI=1.21–1.52; p<0.001) and overall survival (OS) (RR=1.22; 95% CI=1.09–1.37; p<0.001) than the MAC group, similar to the ITC and negative nodes groups. 3) The ITC group had a lower R/P risk and higher 3-year PFS/OS than the MAC group, similar to the negative nodes group. 4) AT reduced the R/P risk in the MM group (RR=0.41; 95% CI=0.22–0.76; p=0.005) and increased 3-year OS in the ITC group (RR=1.06; 95% CI=1.04–1.08; p<0.001). Conclusion Early-stage EC with LVNM had better prognostic outcomes than MAC, and AT may improve outcomes of LVNM patients. More evidence from prospective randomized controlled trials is needed to confirm these findings due to the inherent biases of retrospective studies.

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.