ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

Objective To explore the current status and its influencing factors of electronic health literacy of caregivers of total laryngectomy patients and its influencing factors.Methods A total of 145 caregivers of total laryngectomy patients who were admitted to The First Affiliated Hospital of Naval Medical University from August 2018 to August 2023 were selected by convenience sampling.A questionnaire survey was conducted on these caregivers by demographic data questionnaire,electronic health literacy scale(e-HLS),and general self-efficacy scale.Results The average total score of electronic health literacy among the caregivers was 25.09±5.31.One-way analysis of variance showed that there were significant differences in the scores of e-HLS among caregivers with different age,education level,self-efficacy,frequency of online health information search,and disease course(P<0.05).Multivariate logistic regression analysis showed that age,education level,self-efficacy,frequency of online health information search,and disease course were the main factors affecting the electronic health literacy of caregivers of total laryngectomy patients.Conclusion Electronic literacy of caregivers of total laryngectomy patients is at a low level,and it was affected by many factors.Appropriate guidance can be provided to caregivers with low electronic health literacy,so as to improve the electronic health literacy of caregivers and the quality of care for total laryngectomy patients.

Background and Aims:Laparoscopic cholecystectomy(LC)is a common surgical method for the treatment of gallbladder diseases.However,some patients experience symptoms such as dyspepsia after surgery,which can affect their quality of life.Compound azinomide enteric-coated tablets,a novel drug,may improve dyspeptic symptoms after LC.This study was conducted to explore the clinical efficacy of compound azinomide enteric-coated tablets in treating post-LC dyspepsia symptoms through a multicenter clinical trial.Methods:A multicenter,superior efficacy,open-label,parallel-controlled design was used.Patients with postoperative dyspepsia were enrolled in 7 centers between January 2023 and May 2024.Patients were randomly assigned to either the observation or control groups using a random number table.The observation group received compound azinomide enteric-coated tablets,while the control group was treated with a combination of oryzae pancreatin tablets and ursodeoxycholic acid tablets.Both groups were treated for 4 weeks.The primary endpoints included gastrointestinal symptom scores and quality of life scores assessed before and at 14 and 28 d after treatment.Additionally,the incidence of adverse reactions and cost-effectiveness ratio(CER)were compared between the groups.Results:A total of 303 patients were included,with 150 in the observation group and 153 in the control group.Baseline characteristics were balanced between the groups before treatment(all P>0.05).After treatment,the observation group showed significantly higher effective rates at 14 d and 28 d than the control group(44.7%vs.29.4%;98.0%vs.73.9%,both P<0.05).The observation group also had significantly lower symptom scores and quality of life scores at both 14 and 28 d,with a significantly higher improvement rate in symptom scores compared to the control group(all P<0.05).Further analysis of the improvement rate and treatment efficacy for individual symptoms revealed that,except for the 14-d improvement in abdominal pain/discomfort,the observation group showed better improvement in all other symptoms at 14 d and in all symptoms at 28 d compared to the control group(all P<0.05).No adverse reactions were observed in either group.The CER for the observation group was 283.78 yuan/efficacy rate at 14 d and 128.57 yuan/efficacy rate at 28 d,while the control group's CER was 729.93 yuan/efficacy rate at 14 d and 290.22 yuan/efficacy rate at 28 d.Conclusion:Compound azinomide enteric-coated tablets demonstrated good clinical efficacy in treating dyspepsia symptoms after LC with excellent safety and high cost-effectiveness.Despite some limitations,the results provide a new treatment option for dyspepsia after LC.Larger-scale randomized controlled trials are needed to validate this study's conclusions further.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Temporomandibular joint osteoarthritis is a common chronic degenerative disease,in which joint pain is the most signif-icant symptom,but its pathogenesis is still unclear.Significant subchondral bone lesions can occur in the early stage of osteoarthritis progression,and more and more experimental evidence shows that subchondral bone lesions play an important role in the pain caused by osteoarthritis.Osteoclasts,osteocytes,osteoblasts,endothelial cells,new generating nerves and blood vessels in the sub-chondral bone matrix microenvironment interact with each other and participate in the process of osteoarthritis pain.Therefore,regu-lating the subchondral bone matrix microenvironment is expected to become a new strategy to control joint pain.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To investigate the protective effect of fluoxetine on neurons in rats with subarachnoid hemorrhage (SAH) and explore its mechanism based on the chemokine receptor 4 (CXCR4)/nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) pathway.Methods:Seventy-five rats were randomly divided into a normal control group and a model group. The SAH model was established by the internal carotid artery puncture method in the model group. After modeling, rats were randomly divided into the model group, fluoxetine low-, medium-, and high-dose groups, and nimodipine group, with 12 rats in each group. The fluoxetine low-, medium-, and high-dose groups were intravenously injected with fluoxetine at doses of 5, 10, and 15 mg/kg, respectively; the nimodipine group was intraperitoneally injected with nimodipine at 0.2 mg/kg; the normal control group and model group were intraperitoneally injected with an equal volume of normal saline, once a day for 7 consecutive days. The shuttle box was used to determine the number of avoidance responses and avoidance response time of rats. The water content of brain tissue and Evans blue exudation volume were calculated. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in the hippocampal tissue. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal tissue. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA levels of CXCR4 and NLRP1 in the hippocampal tissue. Western blot was used to determine the protein levels of CXCR4, NLRP1, LC3-Ⅱ, and Beclin1 in the hippocampal tissue.Results:Compared with the normal control group, the model group had a lower number of avoidance responses, lower levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were higher (all P<0.05). Compared with the model group, the fluoxetine groups (all doses) and nimodipine group had a higher number of avoidance responses, higher levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were lower (all P<0.05); moreover, the changes in various indicators were more significant with the increase of fluoxetine dose. HE staining results showed that there were no pathological changes in the hippocampal tissue of the normal control group; in the model group, the number of hippocampal neurons decreased, nuclei were pycnotic, and cell arrangement was irregular. Compared with the model group, the number of hippocampal neurons increased, cell arrangement was regular, and hippocampal pathology was significantly restored in the fluoxetine groups (all doses) and nimodipine group. Conclusions:Fluoxetine can significantly alleviate the pathological progression of cerebral edema, repair neuronal damage, improve neurological function, and regulate mitochondrial autophagy in SAH rats, whose mechanism may be related to the regulation of the CXCR4/NLRP1 pathway.