OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.

The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapa-mycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.

OBJECTIVE To explore the characteristics of adverse drug reaction （ADR） induced by semaglutide and provide a reference for clinically safe medication. METHODS Using search terms such as “semaglutide” and “adverse reactions” in both Chinese and English， the case reports about ADRs caused by semaglutide were searched and analyzed from PubMed， Web of Science， SpringerLink， CNKI， Chinese Medical Journal Full-text Database， Wanfang Medical Network and VMIS. RESULTS Overall 14 literature were included， involving 17 patients. Among 17 patients， 9 were female and 8 were male， with the age ranging from 25 to 80 years. Eight patients were given two or more drugs， and eight patients took 0.25 mg as the initial dose； the ADR occurred most frequently within 6 months （94.12%）. Sixteen patients’ symptoms improved or recovered after drug withdrawal and symptomatic treatment. Eleven patients did not mention whether to continue to use semaglutide in the future. Nine patients underwent ADR correlation evaluation， and 1， 3， 1 and 4 cases were determined to be “definite”，“ probable”，“ possible”， and “doubtful” respectively. Semaglutide-induced ADRs involved multiple organs or systems， most of which were the digestive system （35.29%）， followed by skin tissue （29.41%）. Among them， acute gastric dilation， severe liver injury， calculous cholecystitis， bullous pemphigoid， eosinophilic fasciitis， acute kidney injury， acute interstitial nephritis， depression and acute hemolytic anemia were not mentioned in the instruction. CONCLUSIONS ADRs caused by semaglutide can occur in all ages， mainly within 6 months after medication， and mainly involve the digestive system， skin tissue， etc. Great attention should be paid to pharmaceutical care for those patients with liver and kidney dysfunction， neuropsychiatric diseases， glucose-6-phosphate dehydrogenase deficiency， etc. When ADR occurs， drug withdrawal and symptomatic treatment should be performed promptly to ensure patients’ medication safety.

Objective:To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children.Methods:Clinical characteristics of 4 AFM cases from Department of Neurology, Children′s Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively.Results:The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children.Conclusions:AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.

Objective To analyze the status of occupational hazards in key positions of the small and micro book and newspaper printing enterprises in Beijing City. Methods A total of 16 small and micro printing enterprises in Beijing City were selected as the research subjects using the judgment sampling method. The status of occupational hazard was assessed using on-site occupational health investigations. The volatile chemical components in organic solvents such as inks and cleaning agents used in the workplace, the level of chemical hazardous agents in the air, and noise intensity were detected and analyzed. Results A total of 1 105 workers from 16 small and micro printing enterprises were included. The occupational hazard exposure rate was 22.2% (245/1 105), with chemical hazardous agents and noise exposure rates of 13.5% and 22.2%, respectively. The rate of compliance with occupational health training among the head of the enterprise and the occupational health management personnel, the regular detection rate of occupational hazards in last year, and the rate for the occupational health examination in last year were both 100.0%. The rate for annual update of occupational hazard project reporting was 93.8% (15/16). The usage rates of gas mask and noise-proof earplug were 68.8% (11/16) and 50.0% (8/16), respectively. The effectiveness rates of anti-toxic and noise-reduction facilities were 87.5% (14/16) and 62.5% (10/16). The sign setting rates of chemical hazardous agents and noise warning were 93.8% (15/16). Acetone and isopropanol were found in ink and cleaning agents in 15 printing enterprises, while toluene, xylene, and ethylbenzene were found in three, two, and one enterprise, respectively. Benzene, 1,2-dichloroethane, n-hexane, and trichloroethylene were not found in all 16 enterprises. Both the exposure concentration of short term and exposure concentration of time weighted average of the above chemical hazards were lower than the lower limit of quantitation of the detection method in the workplace and work site air among the 16 printing enterprises, and none of concentration was exceeded the national standard. A total of 240 noise work sites were detected, and the national noise-exceeding rate was 11.2%(27/240). Conclusion Noise hazards are prominent in the small and micro printing enterprises in Beijing City, and attention should be paid to the prevention and protection of noise-exposure. The usage rate of personal protective equipment is not high, and the training and on-site supervision management of protective equipment wearing in workers should be strengthened.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.

Objective:To investigate the effects of matrine on proliferation, apoptosis and radiotherapy sensitivity of uveal melanoma cells.Methods:An animal experiment study. In vitro experiment: MuM2B cells of human choroidal melanoma were randomly divided into control group and matrine 0.25, 0.50, 1.00, 2.00 g/L groups. The cell morphology was observed by transmission electron microscope. Cell proliferation was detected by thiazole blue colorimetry. The mRNA and relative expression levels of CyclinD D (CyclinD), B lymphoblastoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) were detected by real-time polymerase chain reaction and Western blot. In vivo experiment: BALB/C mice were injected with MuM2B cell suspension subcutaneously on the back of forelimb to prepare transplanted tumor model. After successful modeling, they were randomly divided into blank group and matrine treatment group with different concentrations. Mice in blank group were injected with phosphate buffer subcutaneously. Mice in different matrine treatment groups were injected with 15, 25, 50, 100 mg/kg matrine subcutaneously, respectively, for 7 consecutive days. The tumor was weighed and its volume was measured after the last administration. Single factor analysis of variance was used to compare different groups. The t test was used for pairwise comparison between groups. Results:In the control group, the cell structure was normal, the distribution was uniform, and no or rare nuclear pyknosis was seen. With the increase of matrine dosage, the nuclear pyretosis increased gradually and cell morphology changed obviously. Compared with the control group, the cell survival rate in 0.50, 1.00 and 2.00 g/L groups gradually decreased with matrine concentration increasing and treatment time prolongating, the relative expression levels of CyclinD and Bcl-2 mRNA and protein gradually decreased, and the relative expression levels of Bax mRNA and protein gradually increased. Under the same radiation dose X-ray irradiation, the cell survival rate of 0.50, 1.00 and 2.00 g/L groups gradually decreased, and the differences were statistically significant ( P<0.05). Compared with blank group, the tumor weight and volume of mice in different doses of matrine group were significantly decreased, and the differences were statistically significant ( P<0.05). Conclusion:Matrine can down-regulate the expression of CyclinD and Bcl-2, up-regulate the expression of Bax, promote the apoptosis of MuM2B human melanoma cells, inhibit cell proliferation, and enhance cell radiosensitivity.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.