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.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Objective Through molecular genetics analysis of a calculi family lineage,this study aims to explore its pathogenesis and the association between genotypes and phenotypes.Methods A retrospective analysis was conducted on a calculi family lineage admitted to Tongji Hospital,affiliated with Tongji Medical College,Huazhong University of Science and Technology.Clinical data and peripheral blood samples of the affected children and some family members were collected.Whole exome sequencing was performed,followed by Sanger sequencing to validate the candidate variants.Results Among the 38 family members across four generations,10 members were diagnosed with calculi disease.The second generation,member 2(Ⅱ-2),third generation,member 2(Ⅲ-2),and third generation,member 4(Ⅲ-4)suffered from recurrent multiple kidney stones and gallstones.The second generation,member 6(Ⅱ-6),second generation,member 13(Ⅱ-13),and third generation,member 5(Ⅲ-5)had recurrent multiple kidney stones alone,while first generation,member 2(Ⅰ-2),second generation,member 4(Ⅱ-4),second generation,member 8(Ⅱ-8),and second generation,member 11(Ⅱ-11)only had gallstones.No other family members exhibited any signs of kidney or gallbladder involvement.Ⅱ-2 was diagnosed in 2018 with end-stage renal disease stage 5,grade 3 hypertension and gallstones,urinary amino acid high-performance liquid chromatography analysis indicated elevated urinary cystine.This member had a history of recurrent multiple kidney stones and recurrent urinary tract infections for over 30 years,with multiple histories of ureteroscopic stone removal.Genetic analysis revealed that Ⅱ-2,Ⅲ-2,Ⅲ-4,Ⅲ-5 and Ⅳ-1 all carry a heterozygous mutation in exon 10 of the solute carrier family 3 member 1(SLC3A1)gene,c.1889G＞A(p.Gly630Asp).The third generation,member 1(Ⅲ-1),and fourth generation,member 2(Ⅳ-2),are wild type.This mutation shows a phenomenon of family co-segregation.Conclusions The heterozygous mutation of SLC3A1 gene,c.1889G＞A,may be the genetic cause of calculi disease in multiple members of this family lineage.Recurrent multiple kidney stones and/or gallstones require high attention to genetic etiology.It is recommended to perform genetic analysis on calculi family lineages and patients with early-onset calculi disease.

Objective To observe the efficacy,safety,and compliance of lamotrigine combined with magnesium valproate in treating children with depressive episodes of bipolar disorder,and to explore the effects on thyroid hormone levels,brain-derived neurotrophic factor(BDNF),C-reactive protein(CRP),interleukin-1(IL-1),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and plasma concentration of valproate.Methods The children with bipolar disorder diagnosed from January 2023 to February 2025 were selected,and divided into the observation group and control group.The control group was treated with magnesium valproate tablets,and the observation group was added lamotrigine in addition to the treatment given to the control group.Both groups were treated continuously for 8 weeks.The clinical efficacy,the Hamilton Depression Scale-24(HAMD-24)score,Clinical Global Impression(CGI)assessment,thyroid hormone levels,BDNF,CRP,IL-1,IL-10 and TNF-α,daily average dose of magnesium valproate(D),blood concentration of valproate(C),C/D ratio,mean dosing interval(h),incidence of adverse reactions,and medication adherence and satisfaction scores in both groups was observed.Results A total of 100 children were included,50 in each group.After treatment,the total effective rate of the observation group was 98.00％which was significantly higher than that of the control group(84.00％)(P＜0.05).The serum free triiodothyronine(FT3),free thyroxine(FT4),BDNF and IL-10 in both groups increased compared to the previous(P＜0.05),while HAMD-24 score,CGI score,thyroid-stimulating hormone(TSH),CRP,IL-1 and TNF-α decreased(P＜0.05),and all indicators in the observation group were better than those in the control group(P＜0.05).Both groups had no serious or new adverse drug reactions,and the incidence of total adverse reactions,the difference in the incidence of total adverse reactions was not statistically significant(P＞0.05).There was no statistically significant difference in valproic acid blood concentrations between the two groups of children(P＞0.05).The medication compliance score and satisfaction score of the observation group were significantly higher than those of the control group(P＜0.05).Conclusion Combination of lamotrigine with magnesium valproate in children with depressive episodes of bipolar disorder improves treatment effective and clinical symptoms,promotes a rise in thyroid hormone and BDNF as well as improves inflammatory factors and increases medication adherence and satisfaction in children with a better safety profile.

Objective To observe the efficacy,safety,and compliance of lamotrigine combined with magnesium valproate in treating children with depressive episodes of bipolar disorder,and to explore the effects on thyroid hormone levels,brain-derived neurotrophic factor(BDNF),C-reactive protein(CRP),interleukin-1(IL-1),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and plasma concentration of valproate.Methods The children with bipolar disorder diagnosed from January 2023 to February 2025 were selected,and divided into the observation group and control group.The control group was treated with magnesium valproate tablets,and the observation group was added lamotrigine in addition to the treatment given to the control group.Both groups were treated continuously for 8 weeks.The clinical efficacy,the Hamilton Depression Scale-24(HAMD-24)score,Clinical Global Impression(CGI)assessment,thyroid hormone levels,BDNF,CRP,IL-1,IL-10 and TNF-α,daily average dose of magnesium valproate(D),blood concentration of valproate(C),C/D ratio,mean dosing interval(h),incidence of adverse reactions,and medication adherence and satisfaction scores in both groups was observed.Results A total of 100 children were included,50 in each group.After treatment,the total effective rate of the observation group was 98.00％which was significantly higher than that of the control group(84.00％)(P＜0.05).The serum free triiodothyronine(FT3),free thyroxine(FT4),BDNF and IL-10 in both groups increased compared to the previous(P＜0.05),while HAMD-24 score,CGI score,thyroid-stimulating hormone(TSH),CRP,IL-1 and TNF-α decreased(P＜0.05),and all indicators in the observation group were better than those in the control group(P＜0.05).Both groups had no serious or new adverse drug reactions,and the incidence of total adverse reactions,the difference in the incidence of total adverse reactions was not statistically significant(P＞0.05).There was no statistically significant difference in valproic acid blood concentrations between the two groups of children(P＞0.05).The medication compliance score and satisfaction score of the observation group were significantly higher than those of the control group(P＜0.05).Conclusion Combination of lamotrigine with magnesium valproate in children with depressive episodes of bipolar disorder improves treatment effective and clinical symptoms,promotes a rise in thyroid hormone and BDNF as well as improves inflammatory factors and increases medication adherence and satisfaction in children with a better safety profile.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

Objective Through molecular genetics analysis of a calculi family lineage,this study aims to explore its pathogenesis and the association between genotypes and phenotypes.Methods A retrospective analysis was conducted on a calculi family lineage admitted to Tongji Hospital,affiliated with Tongji Medical College,Huazhong University of Science and Technology.Clinical data and peripheral blood samples of the affected children and some family members were collected.Whole exome sequencing was performed,followed by Sanger sequencing to validate the candidate variants.Results Among the 38 family members across four generations,10 members were diagnosed with calculi disease.The second generation,member 2(Ⅱ-2),third generation,member 2(Ⅲ-2),and third generation,member 4(Ⅲ-4)suffered from recurrent multiple kidney stones and gallstones.The second generation,member 6(Ⅱ-6),second generation,member 13(Ⅱ-13),and third generation,member 5(Ⅲ-5)had recurrent multiple kidney stones alone,while first generation,member 2(Ⅰ-2),second generation,member 4(Ⅱ-4),second generation,member 8(Ⅱ-8),and second generation,member 11(Ⅱ-11)only had gallstones.No other family members exhibited any signs of kidney or gallbladder involvement.Ⅱ-2 was diagnosed in 2018 with end-stage renal disease stage 5,grade 3 hypertension and gallstones,urinary amino acid high-performance liquid chromatography analysis indicated elevated urinary cystine.This member had a history of recurrent multiple kidney stones and recurrent urinary tract infections for over 30 years,with multiple histories of ureteroscopic stone removal.Genetic analysis revealed that Ⅱ-2,Ⅲ-2,Ⅲ-4,Ⅲ-5 and Ⅳ-1 all carry a heterozygous mutation in exon 10 of the solute carrier family 3 member 1(SLC3A1)gene,c.1889G＞A(p.Gly630Asp).The third generation,member 1(Ⅲ-1),and fourth generation,member 2(Ⅳ-2),are wild type.This mutation shows a phenomenon of family co-segregation.Conclusions The heterozygous mutation of SLC3A1 gene,c.1889G＞A,may be the genetic cause of calculi disease in multiple members of this family lineage.Recurrent multiple kidney stones and/or gallstones require high attention to genetic etiology.It is recommended to perform genetic analysis on calculi family lineages and patients with early-onset calculi disease.

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 579329.54 yuan,and the accumulative utility was 8.0524 quality-adjusted life year (QALYs);the accumulative cost of finerenone combined with the standard treatment regimen was 332520.61 yuan,and the accumulative utility was 8.1874 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.

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

Objective:To study the variational trend in disease characteristics of patients with hepatitis B-related primary liver cancer (HBV-HCC) in the past five years.Method:A single-center retrospective cross-sectional analysis was performed to compare patients diagnosed with HBV-HCC from January 2012 to December 2016 (control group) and from January 2017 to December 2021 (observation group). The data of the study variables were extracted from the electronic medical record system of the hospital information system of the Second Hospital of Lanzhou University. The 1:2 propensity score matching was used to adjust potential confounding factors such as gender and age. Multivariate logistic regression analysis was used to study the factors affecting changes in disease characteristics of the HBV-HCC population in the observation group. GraphPad Prism 8.0 software was used to draw forest plots to intuitively display the effect size of the study variables in the logistic regression analysis.The t-test was used to compare normally distributed data between groups. The χ2 test was used for inter-group comparison. Results:A total of 1 717 eligible cases were collected, including 510 in the control group and 1 207 in the observation group. Compared with the control group, the number of newly diagnosed cases in the observation group increased by 2.36 times, and males were still the main onset population (83.3% vs. 82.7%). The median age of onset increased (51.9 vs. 53.5 years, P<0.001). 79.4% of HBV-HCC patients had not received antiviral therapy, and the proportion of HBeAg-negative patients increased (56.4%). The factors affecting HBV-HCC patients included family history of HBV ( OR=1.626, 95% CI: 1.181-2.238), family history of hepatocellular carcinoma ( OR=1.388, 95% CI: 1.013-1.901), hypoviremia ( OR=1.322, 95% CI: 1.046-1.671), abnormal alanine aminotransferase ( OR=1.545, 95% CI: 1.231-1.940), liver fibrosis ( OR=1.478, 95% CI: 1.153-1.894), liver cirrhosis ( OR=1.431, 95% CI: 1.128-1.815), and metabolic-related fatty liver disease ( OR=1.438, 95% CI: 1.116-1.815) after propensity score matching adjustment. The factors affecting HBeAg-positive patients were decreased ( OR=0.390, 95% CI: 0.389-0.617); however, the number of early HBV-HCC diagnoses was increased (12.7% vs. 19.3%, P=0.001). Conclusion:The characteristics of patient disease and occurrence of HBV-HCC are changing over the past five years. The risk of developing hepatocellular carcinoma in middle- to older male patients with chronic hepatitis B is increasing with familial history of HBV and hepatocellular carcinoma, HBeAg negativity, hypoviremia, abnormal alanine aminotransferase, liver fibrosis, cirrhosis, and metabolic-related fatty liver disease.