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.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

Coronary heart disease （CHD） has a distinct circadian rhythmicity in its onset， which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind"， this paper explores the pathogenic evolution rules of qi-blood disharmony， channel obstruction， interacting as cause and effect with circadian rhythm disorders in CHD. Clinically， CHD can be observed to attack in the early morning， at night， in the afternoon， and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation， yin deficiency with yang floating， qi and yin deficiency， and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time， regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages， and select the appropriate timing for administration to harness natural timing. At the Mao （卯） hour， yang ascends while yin descends， and taking medication at this time conforms to the ascending of yang qi. At the Wu （午） hour， the heart meridian is active， and taking medication at this time warms the channel passages and assists heart yang， which can be treated with modified Buzhong Yiqi Decoction （补中益气汤） or Shengyang Yiwei Decoction （升阳益胃汤）. At night， blood should be harmonized， when the channel passages are unblocked through nourishing， restraining， and searching， with Lianmei Decoction （连梅汤） combined with Dahuang Zhechong Pill （大黄䗪虫丸）. Following the temporal rhythm， the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises， resonating and corresponding with the natural rhythm.

OBJECTIVE To provide guidance for the individualized use of antiepileptic drugs （AEDs） in patients with epilepsy or bipolar affective disorder.METHODS Clinical data of patients with epilepsy or bipolar affective disorder who received AEDs treatment and underwent therapeutic drug monitoring （TDM） at Xi’an International Medical Center Hospital from January 2023 to December 2025 were retrospectively collected. The baseline information， characteristics of AEDs utilization， implementation status of TDM and laboratory parameters were summarized. Spearman correlation analysis， univariate analysis and multivariate linear regression analysis were performed to identify the independent influencing factors for blood concentrations of AEDs.RESULTS A total of 1 572 patients were enrolled， including 660 males and 912 females. The majority were aged ≥60 years （30.15%）； 71.76% of patients were on monotherapy with AEDs， with valproic acid being the most commonly prescribed （51.97%）； combination therapy was predominantly a two-drug regimen （26.21%）， while three-drug regimens were rare （2.04%）. A total of 2 901 blood samples for TDM were collected， with the highest number of samples for valproic acid and levetiracetam （1 987 and 684 samples， respectively）. TDM for all five drugs was primarily conducted once； among which， the blood concentrations attainment rates exceeded 50% for patients taking valproic acid and levetiracetam， while the median blood concentrations for patients taking lamotrigine， oxcarbazepine， and carbamazepine were all below the lower limit of the therapeutic reference range. Based on the results of Spearman correlation analysis， univariate analysis， and multivariate linear regression analysis， patient gender， platelet count （PLT）， alanine transaminase （ALT）， aspartate transaminase （AST）， and total bilirubin （TBil） were found to be independent factors influencing blood concentration of valproic acid （unstandardized coefficients were －6.770 7， －0.078 6， －0.099 4， 0.083 2， －0.578 9， P ＜0.05）， while age and creatinine （CRE） were found to be independent factors influencing blood concentration of levetiracetam （unstandardized coefficients were 0.108 7， 0.047 8， P ＜0.05）.CONCLUSIONS Female gender and elevated AST levels are risk factors for increased blood concentration of valproic acid， while elevated PLT， ALT and TBil levels are associated with decreased blood concentration of valproic acid. Patients of advanced age and those with renal insufficiency bear a relatively high risk of in vivo levetiracetam accumulation.

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: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged