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.

AIM:To automatically identify and quantitatively assess myopia-related fundus structural changes by combining non-mydriatic color fundus photography with an artificial intelligence(AI)-powered quantitative fundus analysis system and to further analyze the correlations between these fundus parameters and spherical equivalent(SE), axial length(AL), and age, providing the objective basis for monitoring myopia progression and supporting the formulation of personalized myopia prevention and control strategies. METHODS:A cross-sectional study was conducted enrolling myopic patients aged 18-50 y who underwent myopia screening from March 2023 to December 2023. Patients were stratified into three groups based on SE: the -3.00 D

Objective To study the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway. Methods Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group (400 mg/kg), low, medium and high dose groups of Lishukang capsule (400、 600、 800 mg/kg), with 10 mice in each group. The normal control group was fed at the local altitude (1 500 m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500 m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given normal saline once a day, and 1 hour after the last administration, the eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice. Results Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased （P<0.01）. Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased（P<0.01）. Conclusion High altitude hypoxia can lead to oxidative stress injury in mice and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment in mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.

Objective To evaluate the characteristics, related therapeutic regimens, risk factors of cardiovascular adverse events (CVAEs) and prognosis in the current therapy of newly diagnosed multiple myeloma (NDMM) patients in China. Methods A retrospective observational study was performed on patients with NDMM treated at Zhongshan Hospital, Fudan University, from January 2013 to October 2021. The propensity score matching at a ratio of 1∶1 was employed to balance baseline confounders between the therapeutic group and the control group, and CVAEs incidences were compared between the corresponding groups. Independent risk factors for CVAEs were identified through Fine-Gray competing risk regression model. Kaplan-Meier survival curves and log-rank tests were used to assess overall survival and progression-free survival of patients. Results A total of 829 patients with NDMM were analyzed, with a median of 33.1 months of follow-up for survivors. CVAEs occurred in 65 patients (7.8%) during first-line treatment, and a total of 74 events were recorded, with 52.7% grade 3 or greater in severity. Arrhythmia (particularly atrial fibrillation), thrombotic event (TE), and heart failure were the most common types. The median time from treatment to the first occurrence of CVAEs was 26 days, while the medium occurrence time of TE was later than the other events (76 d vs 19 d, P＝0.003). The exposure to immunomodulatory drugs was related to a higher incidence of TEs, whereas other therapeutic regimens, including bortezomib, didn’t show the effect of cardiovascular toxicity. Results of multivariate analysis showed that Eastern Cooperative Oncology Group performance status ＞2, symptomatic heart diseases within three months before treatment, and estimated glomerular filtration rate≤50 mL·min⁻¹·(1.73 m²)⁻¹ were independent risk factors for CVAEs. Compared with patients without CVAE, patients who experienced CVAEs had significantly inferior progression-free survival and overall survival, and higher cardiovascular mortality (P＜0.001). Conclusions The incidence of CVAE is relatively high during first-line treatment in NDMM patients, and the prognosis of CVAE patients is poor. The risk of CVAE is significantly increased in patients with underlying cardiovascular diseases.

Objective:To explore the correlation between IκB kinase-interacting protein(IKBIP)expression in tumor cells within cervical cancer tissues(TCCCT)and the clinical pathological characteristics and prognosis of patients,as well as its impact on the biological behaviors of cervical cancer(CC)cells HeLa and SiHa,and to elucidate its potential mechanism.Methods:GENT2 and Kaplan-Meier plotter databases were utilized to analyze the differential expression of IKBIP mRNA in CC and normal cervical tissues,as well as its correlation with the clinical prognosis of CC patients.The Hallmark reference gene set was chosen for pathway enrichment analysis using the Gene Set Enrichment Analysis(GSEA)software.Immunohistochemistry method was used to detect the IKBIP protein expression in TCCCT and epithelial cells in normal cervical tissue(ECNCT),and analyze the correlations between its expression level and clinicopathological characteristics and prognosis of CC patients.Furthermore,univariate and multivariate Cox regression analyses were performed to identify the risk factors impacting the prognosis of CC patients.The stably transfected cells of CC(HeLa cells and SiHa cells)with IKBIP knockdown were established for the experiment,which were divided into sh-NC group and sh-IKBIP group.The expression of IKBIP protein in various groups was assessed using Western blotting method.The cell proliferation activity and the percentage of 5-ethynyl-2'-deoxyuridine(EdU)positive cells were measured using cell counting kit-8(CCK-8)and EdU methods,while Transwell chamber assay was employed to determine the numbers of migration and invasion cells in various groups.Additionally,the expression levels of E-cadherin,N-cadherin,and Snail proteins in the cells in various groups were analyzed by Western blotting method.Results:The GENT2 database analysis revealed that the expression level of IKBIP mRNA in CC tissue was higher than that in normal cervical tissue(P＜0.001).The GSEA enrichment analysis identified the epithelial-mesenchymal transition(EMT)pathway as the top-ranked pathway in IKBIP high-expression group.The immunohistochemistry results indicated the positive expression rate of IKBIP protein in TCCCT was higher than that in ECNCT(50.5％vs 8.0％),and its over-expression was associated with FIGO stage(2018)and differentiation grade of tumor(P＜0.05).The univariate and multivariate Cox regression analyses suggested that lymph node metastasis(LNM)and high expression of IKBIP were the risk factors affecting the overall survival(OS)and progression-free survival(PFS)of CC patients(P＜0.05).The Western blotting method results showed that compared with sh-NC group,the expression level of IKBIP protein in the cells in sh-IKBIP group was decreased(P＜0.05).The CCK-8 and EdU assay results showed that compared with sh-NC group,the proliferation activity and the percentage of EdU positive cells in sh-IKBIP group were decreased(P＜0.05).The Transwell chamber assay results showed that compared with sh-NC group,the numbers of migration and invasion cells in sh-IKBIP group were significantly decreased(P＜0.05).Additionally,the Western blotting method results indicated that compared with sh-NC group,the expression level of E-cadherin protein in sh-IKBIP group in CC cells was increased(P＜0.05),while the expression levels of N-cadherin and Snail protein were decreased(P＜0.05).Conclusion:The expression of IKBIP protein is significantly up-regulated in HeLa and SiHa cells derived from CC,and it is closely correlated with poor prognosis in CC patients.Suppression of IKBIP protein expression can effectively inhibit the proliferation,invasion and migration capabilities as well as EMT process of CC cells.

Objective:To evaluate the effect of preoperative neoadjuvant chemotherapy on rocuronium bromide-induced neuromuscular blockade in patients undergoing radical resection of gastrointestinal tumors.Methods:In this retrospective cohort study, the medical records from patients pathologically diagnosed with gastrointestinal tumors (stageⅡ or Ⅲ) and underwent elective radical tumour resection under general anaesthesia, aged 43-74 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ at Shaanxi Provincial People′s Hospital from November 2021 to November 2022, were collected. The patients were divided into 2 groups based on whether preoperative neoadjuvant chemotherapy was performed: non-chemotherapy group and chemotherapy group. Non-chemotherapy group did not receive neoadjuvant chemotherapy before surgery and underwent direct surgery without receiving neoadjuvant chemotherapy. Chemotherapy group received 4 weeks of chemotherapy with FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), XELOX (capecitabine + oxaliplatin) or SOX (oxaliplatin + tegio) the three regimens before surgery. The neuromuscular monitoring was initiated after induction of intravenous anaesthesia, and rocuronium bromide 0.6 mg/kg was intravenously injected when the train-of-four ratio stabilized at 90%-110%. Mechanical ventilation was performed after endotracheal intubation when the train-of-four count was 0. When T 1 began to recover, rocuronium 0.2 mg/kg was intravenously injected, and rocuronium was intermittently injected during operation to maintain muscle relaxation. The onset time, complete muscle relaxation time, recovery index, 90% recovery index, maintenance time and consumption of rocuronium were recorded. Results:A total of 40 patients were finally included, with 20 in each group. Compared with non-chemotherapy group, the onset time was significantly prolonged, the recovery index, 90% recovery index and consumption of rocuronium were increased, the time for complete muscle relaxation was shortened ( P<0.05), and no significant change was found in the maintenance time of muscle relaxation in chemotherapy group ( P>0.05). Conclusions:Preoperative neoadjuvant chemotherapy can prolong the onset and recovery time of rocuronium, shorten the time to complete muscle relaxation and increase the consumption in patients undergoing radical resection of gastrointestinal tumors.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Objective:To evaluate the efficacy and safety of Luofuoshan-Baicao oil (LBO) and wind medicated oil for the treatment of Aedes albopictus bites. Methods:A paired self-controlled study was conducted. Thirty-six healthy volunteers were recruited from Guangdong Provincial Hospital of Traditional Chinese Medicine from February 2023 to March 2023. Each participant's forearms were subjected to Aedes albopictus bites, with 3 bites on each arm. For the first 18 participants, LBO was applied to the left arm, and wind medicated oil to the right arm; for the latter 18 participants, wind medicated oil was applied to the left arm, and LBO to the right arm. The observation period was 24 hours. Within the first 3 hours after the mosquito bites, the topical agents were applied once every other hour for a total of 3 sessions, with an applicator centered on the bite site at a dose of approximately 50 μl, covering a skin area of about 2 cm in diameter; after 3 hours, participants applied the topical agents themselves until symptoms subsided or the 24-hour observation period ended. All subjects were followed up at the occurrence of skin lesions after mosquito bites, 0 to 3 hours after the first treatment, as well as 24 hours after the first treatment. During the follow-up, the effects of both topical agents on pruritus, erythema, papules, or wheals were evaluated, differences in treatment frequency were analyzed, and treatment-related adverse events were recorded. The time to disappearance of pruritus after treatment was statistically analyzed using Kaplan-Meier survival analysis, and intergroup differences were analyzed using the log-rank (Mantel-Cox) test. Two independent samples t-test was used for comparisons of other measurement data, and Pearson's chi-square test or Fisher's exact test was used for comparisons of count data between groups. Results:Within 3 hours after the first treatment, the time to initial disappearance of pruritus was significantly shorter in the LBO group (20.71 ± 1.92 min) than in the wind medicated oil group (28.30 ± 2.20 min, P < 0.05). The cumulative pruritus rate (the proportion of participants with pruritus among all participants) over time showed an overall stable fluctuation, and the cumulative pruritus rates at all observation points were significantly lower in the LBO group than in the wind medicated oil group ( P<0.05). After 3 hours of treatment, the mean values of changes in erythema diameters were 25.83 mm in the LBO group and 26.24 mm in the wind medicated oil group, while the mean values of changes in papule or wheal diameters were 8.25 mm in the LBO group and 9.18 mm in the wind medicated oil group; within 24 hours after the first treatment, the average time to disappearance of papules or wheals was 71.85 minutes in the LBO group and 73.01 minutes in the wind medicated oil group, while the average time to disappearance of erythema was 82.27 minutes in the LBO group and 84.86 minutes in the wind medicated oil group; there were no significant differences in the above observational indices between the two groups (all P > 0.05). The number of pruritus episodes within 24 hours of treatment was 56 in both the LBO group and wind medicated oil group, and the treatment frequency was 107 in both two groups; there were also no significant differences in the frequencies of pruritus episodes or treatment (both P > 0.05). No adverse events or reactions occurred during the trial. Conclusion:LBO was more effective than wind medicated oil in reducing the time to disappearance of pruritus after Aedes albopictus bites, with a high safety profile.

Objective:To evaluate the effect of preoperative neoadjuvant chemotherapy on rocuronium bromide-induced neuromuscular blockade in patients undergoing radical resection of gastrointestinal tumors.Methods:In this retrospective cohort study, the medical records from patients pathologically diagnosed with gastrointestinal tumors (stageⅡ or Ⅲ) and underwent elective radical tumour resection under general anaesthesia, aged 43-74 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ at Shaanxi Provincial People′s Hospital from November 2021 to November 2022, were collected. The patients were divided into 2 groups based on whether preoperative neoadjuvant chemotherapy was performed: non-chemotherapy group and chemotherapy group. Non-chemotherapy group did not receive neoadjuvant chemotherapy before surgery and underwent direct surgery without receiving neoadjuvant chemotherapy. Chemotherapy group received 4 weeks of chemotherapy with FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), XELOX (capecitabine + oxaliplatin) or SOX (oxaliplatin + tegio) the three regimens before surgery. The neuromuscular monitoring was initiated after induction of intravenous anaesthesia, and rocuronium bromide 0.6 mg/kg was intravenously injected when the train-of-four ratio stabilized at 90%-110%. Mechanical ventilation was performed after endotracheal intubation when the train-of-four count was 0. When T 1 began to recover, rocuronium 0.2 mg/kg was intravenously injected, and rocuronium was intermittently injected during operation to maintain muscle relaxation. The onset time, complete muscle relaxation time, recovery index, 90% recovery index, maintenance time and consumption of rocuronium were recorded. Results:A total of 40 patients were finally included, with 20 in each group. Compared with non-chemotherapy group, the onset time was significantly prolonged, the recovery index, 90% recovery index and consumption of rocuronium were increased, the time for complete muscle relaxation was shortened ( P<0.05), and no significant change was found in the maintenance time of muscle relaxation in chemotherapy group ( P>0.05). Conclusions:Preoperative neoadjuvant chemotherapy can prolong the onset and recovery time of rocuronium, shorten the time to complete muscle relaxation and increase the consumption in patients undergoing radical resection of gastrointestinal tumors.

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.