OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

[摘 要] 目的：探究着丝粒蛋白M（CENPM）在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制，为脑胶质瘤的精准治疗提供潜在靶点。方法：基于中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞（LN-18、LN-229、U-138MG、U-251MG）和正常胶质细胞（HEB）中的表达；构建CENPM敲低细胞后，通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果：CENPM在WHO高级别胶质瘤中呈高表达（P < 0.05），与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组（P < 0.01），Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素（P < 0.05）。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达，并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞（LN-18：P < 0.01，LN-299：P < 0.05）；敲低CENPM显著抑制迁移（P < 0.05），但增强集落形成，提示其在肿瘤进展中的双重调控作用。结论：CENPM作为胶质瘤独立预后危险因子，通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展，其差异化调控机制（抑制迁移、促进增殖）具有潜在的临床转化价值，可作为分子分型和靶向治疗候选标志物。

The core pathogenesis of attention deficit hyperactivity disorder （ADHD） lies in deficiency， stasis and stagnation. Deficiency arises from kidney essence depletion and spleen dysfunction in transportation and transformation， leading to inadequate nourishment of the marrow sea. Stasis caused by qi deficiency leads to obstruction in channels and collaterals， resulting in obstructed marrow transport. Stagnation is associated with the excess of the five minds transforming into fire， which scorches the brain orifices and leads to loss of control over marrow utilisation. Based on this， a "supplementation-unblocking-regulation" therapeutic approach is proposed. For deficiency， the focus is on supplementing kidney and fortifying spleen， and replenishing the marrow sea. For stasis， the priority is to unblock and open the orifices， and clear the marrow channels. For stagnation， the core is to clear fire and contain the mind， regulate and restore vital activity. In clinical practice， it is necessary to identify the primary and secondary pathogenic mechanisms and apply dynamic， combined treatment， integrating Chinese herbal medicine， acupuncture， and guiding exercises throughout the process， aiming to provide a reference for the diagnosis and treatment of ADHD with traditional Chinese medical.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Heart failure (HF) is a common end-stage clinical manifestation of cardiovascular diseases, imposing substantial health-related burdens worldwide. With its high mortality rates and poor long-term prognosis, there is a pressing need for novel therapies. SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has anti-cardiovascular aging properties and other cardioprotective effects, attracting much research attention in recent years. In addition, SIRT1 plays an important role in HF pathophysiology. This review summarized the roles of SIRT1 and its activators in HF, the changes of SIRT1 gene expression in cardiac tissues from animal models and HF patients, and the current status of clinical trials investigating SIRT1 activators as potential therapies for HF. This will provide new ideas for further exploration of pathological mechanisms and the development of clinical prevention strategies for HF.
Heart Failure/metabolism* ; Sirtuin 1/genetics* ; Humans ; Animals

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*