ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

Objective To evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

OBJECTIVE To study the mechanism of action of Rehmannia glutinosa-medicated serum （RG） in regulating lipopolysaccharide （LPS）-induced polarization of BV2 microglia to interfere with neuroinflammation. METHODS An in vitro neuroinflammation model of BV2 cells induced by LPS was established. Cells were divided into control group， LPS group， 10%RG group， 20%RG group， BAY 11-7082 [nuclear factor kappa B （NF-κB） inhibitor] group， and 20%RG+BAY 11-7082 group. Except for the control group， cells in all other groups were pretreated with corresponding drugs for 12 h and then stimulated with LPS for 24 h. The morphology of cells in each group was observed， and the fluorescence intensity of ionized calcium binding adaptor molecule 1 （Iba-1）， inducible nitric oxide synthase （iNOS）， CD206， the mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， iNOS， IL-4， IL-10， transforming growth factor-β （TGF-β）， arginase-1 （Arg-1）， and the Toll-like receptor 4 （TLR4）/NF-κB/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） signaling pathway-related protein expression were detected. RESULTS Compared with the control group， the LPS group showed significant changes in cell morphology， exhibiting a typical M1 activated morphology. The fluorescence intensity of Iba-1 and iNOS， the relative expression levels of TNF-α， IL-6， IL-1β， iNOS mRNA， the relative expression levels of TLR4， NLRP3， caspase-1 p20， IL-1β p17 protein， and the phosphorylation levels of NF-κB p65 and inhibitor of nuclear factor kappa B α were significantly increased （P＜0.05）. The fluorescence intensity of CD206 and the relative expression levels of IL-4， IL-10， TGF-β， and Arg-1 mRNA were significantly reduced （P＜0.05）. Compared with the LPS group， the changes in the above indicators in the cells of the 10%RG group， 20%RG group， BAY 11-7082 group， and 20%RG+BAY 11-7082 group were significantly reversed （P＜0.05）， and there was no statistically significant difference in the comparison of the last three groups （P＞0.05）. CONCLUSIONS RG can effectively inhibit the overall activation of microglia and correct their M1/M2 polarization imbalance， and its mechanism may be closely related to the inhibition of excessive activation of the TLR4/NF-κB/NLRP3 signaling pathway.

Objective To evaluate the cost-utility of risdiplam in the treatment of pediatric spinal muscular atrophy （SMA） and analyze changes in patients’ out-of-pocket economic burden under the medical insurance scenarios. Methods A Markov model was developed from the healthcare system perspective to compare the long-term costs and quality-adjusted life years （QALYs） of risdiplam treatment versus conventional therapy. The incremental cost-utility ratio （ICUR） was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the model. On this basis, health insurance scenarios were simulated to evaluate patients’ individual economic burden. Results Base-case analysis showed that risdiplam treatment generated additional health benefits but substantially increased medical costs. The resulting ICUR did not demonstrate a clear cost-utility advantage under the current willingness-to-pay threshold. Sensitivity analyses indicated that the model results were relatively robust, with drug costs and key utility parameters being the main drivers of economic outcomes. Health insurance scenario analysis demonstrated that increasing reimbursement levels and reducing patient copayment rates could significantly alleviate patients’ financial burden. Conclusion Risdiplam for pediatric SMA faces economic challenges under the current health insurance payment framework in China. However, optimizing health insurance reimbursement policies and developing multi-tiered healthcare security mechanisms may improve its affordability and accessibility.

Based on the theory of collateral disease， the treatment of late-stage sequela of cerebrovascular disease is considered to be primarily associated with deficiency and obstruction of cerebral collaterals and dysfunction of the spirit mechanism. Therefore， the fundamental therapeutic principle is to unblock and supplement the brain collaterals. Clinically， the late-stage sequelae of cerebrovascular disease are classified into four patterns， which are malnourishment， deficiency-heat， stasis obstruction， and phlegm clouding of brain collaterals. These are treated respectively with Tiansui Tongqiao Decoction （填髓通窍汤） to supplement essence and nourish the brain through moistening， unblocking and supplementing， Qingnao Touluo Decoction （清脑透络汤） to enrich yin， regulate spirit， and unblock collaterals through clearing and penetrating， Yiqi Tongluo Decoction （益气通络汤） to tonify qi and resolve stasis while softening tendons and unblocking collaterals， and Xinrun Touqiao Beverage （辛润透窍饮） to unblock and tonify yin and yang while unblocking the collaterals through acrid-moistening medicinals. Flexible modification of prescriptions according to individual symptoms was applied， resulting in favorable therapeutic outcomes.

Objective: To assess the current status of knowledge, attitude, and practice (KAP) regarding health protection against air pollution among primary school students in China, and to analyze the impacts of fine particulate matter (PM 2.5 ) exposure, family, and individual factors on KAP levels, so as to provide empirical basis for implementing targeted interventions. Methods: Using stratified cluster random sampling method, a questionnaire survey was conducted among 19 297 primary school students from third to fifth grade across 30 provinces (autonomous regions and municipalities directly under the central government) in China in 2024. The questionnaire was developed based on the Technical Guidelines for the Assessment of Civic Environmental and Health Literacy (Trial), and encompasses three dimensions:knowledge, attitude, and practice. Spearman correlation analysis, Chi-square test, multivariate Logistic regression, and Bootstrap mediation effect test was applied for data analysis. Results: The overall mean KAP score for health protection against air pollution among primary school students was (79.73±13.53), with an adequacy rate of 80.47% ( n =15 528). The dimension scores for knowledge, attitude, and practice were (41.34±8.01, 16.43± 2.61 ), and (21.97±5.71), respectively. Knowledge was positively correlated with attitude and practice, and attitude was positively correlated with practice ( r =0.51, 0.35, 0.32, all P <0.01). Multivariate Logistic regression showed that the northeast region ( OR =2.36, 95% CI =2.02-2.75), having parents with a bachelor s degree or higher ( OR =4.76, 95% CI =2.71-8.37), living with both parents ( OR =1.33, 95% CI =1.15-1.55), being in the fifth grade ( OR =1.22, 95% CI =1.11-1.33), outdoor PM 2.5 level exceeding standard limits at the survey site ( OR =1.25, 95% CI =1.16-1.34), history of allergy ( OR =1.47, 95% CI =1.31-1.64), and wearing masks during heavily polluted weather ( OR =1.19, 95% CI =1.07-1.31) were promoting factors for KAP adequacy rate (all P <0.05). Conversely, obesity was a detrimental factor ( OR =0.78, 95% CI =0.69-0.88, all P <0.05). Conclusions Primary school students in China exhibit a favorable KAP level regarding health protection against air pollution, though regional, familial, and individual disparities persist. Exposure to PM 2.5 levels exceeding standard limits exerts a direct positive effect on enhancing health protection literacy. Future efforts should focus on the western region, families with lower educational attainment children to implement tailored, stratified interventions.

ObjectiveTo investigate the effect of growth hormone （GH） pretreatment on the clinical outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer （IVF/ICSI-ET） in patients with diminished ovarian reserve （DOR）. MethodsA retrospective analysis was conducted on the clinical data of 359 DOR patients undergoing IVF/ICSI-ET. Based on the use of GH pretreatment before ovarian stimulation and/or its addition during the stimulation cycle， patients were divided into three groups： the Control group （n=119）， receiving no GH pretreatment or addition； the Non-GH pretreatment group （n=115）， receiving GH （4 IU/d） only during ovarian stimulation without pretreatment； and the GH pretreatment group （n=125）， pretreated with GH （2 IU/d） for 4-6 weeks before stimulation and also receiving GH （4 IU/d） during stimulation. The basic characteristics， ovarian stimulation parameters， embryological data， and cumulative live birth rate （CLBR） were compared among the groups. Results① No significant differences were found among the three groups regarding female age， male age， duration of infertility， body mass index （BMI）， basal hormone levels， distribution of ovarian stimulation protocols， endometrial thickness， serum estradiol （E2） and luteinizing hormone （LH） levels on the day of HCG trigger， or the number of blastocysts transferred per cycle. ② The GH pretreatment group required significantly lower total gonadotropin （Gn） dosage and fewer days of stimulation than the Control and Non-GH pretreatment group（P<0.05）. Compared to the Control group， the GH pretreatment group showed significantly higher numbers of retrieved oocytes， the number of mature oocytes， 2-pronuclei （2PN） zygotes， 2PN cleaved embryos， transferable embryos， high-quality embryos， as well as higher cumulative clinical pregnancy rates and CLBR （P<0.05）. Compared to the Non-GH pretreatment group， the GH pretreatment group had significantly more transferable embryos， high-quality embryos， and a higher CLBR （P<0.05）. ③ Compared to the Control group， the Non-GH pretreatment group only had a significantly higher number of retrieved oocytes （P<0.05）， with no significant differences in the number of mature oocytes， 2PN fertilized oocytes， 2PN cleaved embryos， transferable blastocysts， high-quality blastocysts， cumulative clinical pregnancy rate， and CLBR. ConclusionFor DOR patients， GH pretreatment for 4-6 weeks prior to ovarian stimulation can improve oocyte yield， embryo quality， cumulative clinical pregnancy rate， and CLBR， thereby enhancing the clinical outcomes of IVF/ICSI-ET.

A protection paradox exists in the contemporary legislation of medical assistance in dying （MAID）. That is， whether the legislative option leans toward legalization or absolute prohibition， the original intention of protecting vulnerable groups may contradict itself amid complex social realities. On the one hand， when the law expands autonomous selection through formal empowerment， the socioeconomic status， ability to access resources， and potential discrimination may turn this right into de facto coercion imposed on vulnerable groups. On the other hand， when implementing a ban on MAID to safeguard the right to life， abstract moral imperatives may undermine the authenticity of individual suffering and trigger conflicts between abstract principles and substantive justice. The protection paradox of MAID touches upon the profound challenge of how the law balances universal principles with individual narratives， as well as formal rights with substantive conditions. The key to breaking this dilemma lies in the fact that the legal framework must transcend the simplistic judgment on whether life can be terminated， and turn to construct an institutional design that is sensitive to individual narratives and resilient to structural injustice. This requires the law， while cautiously recognizing MAID under specific circumstances， to strive to strengthen the social support system， ensure equitable access to resources， establish a safeguard mechanism with multi-level assessment and procedural justice， and thereby enable end-of-life decisions to truly become a genuine expression of individual autonomy and life dignity.

AIM:To explore the feasibility of predicting orthokeratology lens ordering parameters(flat K, spherical power, lens diameter, and lens toricity)using the extreme gradient boosting(XGBoost)algorithm based on corneal topographic parameters and basic clinical examination indicators, and to provide references for intelligent clinical fitting.METHODS:Clinical data were retrospectively collected from myopic patients who underwent initial orthokeratology lens fitting and achieved successful fitting at Puyang Second People's Hospital between January 2019 and March 2024. Data from right and left eyes were treated as independent samples, and the dataset was partitioned at the patient level into training and test sets in a 7∶3 ratio. Input features included uncorrected visual acuity(UCVA), axial length(AL), horizontal visible iris diameter(HVID), flat K, steep K, horizontal eccentricity, and vertical eccentricity. The lens toricity prediction model additionally incorporated keratometric astigmatism(ΔK)and surface asymmetry index(SAI). The output labels were the final ordering parameters(flat K, spherical power, lens diameter, and lens toricity). Separate XGBoost regression models were constructed for each output parameter, with hyperparameters optimized independently through grid search combined with 5-fold cross-validation. Model performance was evaluated on the test set using the coefficient of determination(R2), mean absolute error(MAE), and root mean square error(RMSE). Feature importance analysis was also performed.RESULTS:Totally 400 patients(800 eyes)were included in the final analysis. The 400 patients comprised 208 male(52.0%)and 192 female(48.0%)patients, with a mean age of 10.1±2.3 y. After partitioning at the patient level, the training set comprised 280 patients(560 eyes; 146 males and 134 females; mean age 10.1±2.3 y), and the test set comprised 120 patients(240 eyes; 62 males and 58 females; mean age 10.0±2.2 y). No statistically significant differences in sex composition or age were found between the two sets(P>0.05). Toric lenses were used by 140 of the 280 patients(50.0%)in the training set and by 50 of the 120 patients(41.7%)in the test set(χ2=2.017, P=0.156). The flat K prediction model achieved an MAE of 0.34 D and an R2 of 0.84. The spherical power model attained an MAE of 0.43 D and an R2 of 0.70. The lens diameter model yielded an MAE of 0.12 mm and an R2 of 0.42. The lens toricity model(Tweedie regression, power=1.5)achieved an MAE of 0.44 D and an R2 of 0.38. The MAE for each parameter fell within the clinically acceptable tolerance limits(flat K≤0.50 D, spherical power ≤0.75 D, lens diameter ≤0.25 mm, lens toricity ≤0.75 D). Scatter plots and Bland-Altman analysis demonstrated strong agreement between predicted values and actual observations. Feature importance analysis revealed that flat K(0.70)and steep K(0.11)were the most influential predictors in the flat K prediction model.CONCLUSION: The XGBoost model based on routine clinical parameters provides predictions of flat K, spherical power, and lens diameter with MAEs within clinically acceptable ranges, and offers useful reference for cylindrical power prediction. This approach may serve as a useful adjunct to clinical lens fitting. Nevertheless, future prospective studies are warranted to validate its clinical utility in improving actual fitting success rates.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.