ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Patients with craniopharyngioma are at a high risk of developing metabolic dysfunction-associated fatty liver disease and its severe complications， yet this association is often neglected in clinical practice， with a lack of systematic reviews. This article systematically reviews the clinical spectrum and epidemiological characteristics of liver diseases associated with craniopharyngioma， with a focus on their core pathogenic mechanisms， and it also summarizes current tumor treatment strategies aimed at preventing hypothalamic injury and highlights that establishing a multidisciplinary collaborative diagnosis and treatment model and implementing early intervention are key to improving prognosis. Future research should focus on elucidating the precise pathways through which hypothalamic injury leads to metabolic disturbances， thereby facilitating the development of targeted therapies， in order to provide new directions for fundamentally improving the clinical outcomes of these patients.

Objective:To investigate the correlation between the ratio of apolipoprotein B to apolipoprotein A-I (ApoB/ApoA-I) and unstable carotid plaque in a neurologically healthy population receiving health check-ups.Methods:This cross-sectional study consecutively enrolled 1 149 neurologically healthy individuals who underwent physical examinations at the Health Management Centre of Beijing Tiantan Hospital, Capital Medical University, from October 2021 to September 2022. All eligible participants completed standardized questionnaires, physical examinations and laboratory tests. Laboratory tests of lipid metabolism-related biomarkers included total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), ApoA-I, and ApoB; non-high-density lipoprotein cholesterol and the ApoB/ApoA-I ratio were subsequently calculated. The carotid plaque stability was evaluated using superb microvascular imaging technology. The participants were classified into unstable plaque group (341 cases) and stable plaque group (808 cases) according to the presence or absence of intraplaque neovascularization. The univariate and multivariate logistic regression analyses were used to explore the correlation between the ApoB/ApoA-I ratio and unstable carotid plaques.Results:The study enrolled 1 149 participants totally, with a median age of 57 (49-63) years, including 771 males (67.10%) and 378 females (32.90%), and 341 cases (29.68%) were found with unstable carotid plaques. The unstable plaque group had a higher proportion of males, smoking history, diabetes history, along with higher waist-to-hip ratio and ApoB/ApoA-I ratio compared to the stable plaque group [76.54% vs 63.12%, 33.43% vs 22.77%, 19.06% vs 13.37%, 0.91 (0.85, 0.94) vs 0.89 (0.84, 0.93), 0.64 (0.51, 0.76) vs 0.59 (0.48, 0.72)], while HDL-C and ApoA-I levels were lower [1.39 (1.19, 1.63) vs 1.44 (1.24, 1.66) mmol/L, 1.43 (1.29, 1.60) vs 1.51 (1.36, 1.68) g/L] (all P<0.05). An elevated ApoB/ApoA-I ratio was positively associated with the risk of unstable carotid plaque ( OR=1.61, 95% CI: 1.13-2.29, P=0.008; P for trend<0.001). After adjusting for age, gender, waist-to-hip ratio, history of hypertension, history of diabetes, dyslipidemia, cardiovascular disease, history of smoking and estimated glomerular filtration rate, the positive association between elevated ApoB/ApoA-I ratio and the risk of unstable carotid plaque remained significant ( OR=1.48, 95% CI: 1.01-2.16, P=0.044; P for trend=0.004). Conclusion:In a neurologically healthy population receiving health check-ups, an elevated ApoB/ApoA-I ratio may increase the risk of unstable carotid plaque.

Objective To investigate the effects of transcutaneous auricular vagus nerve stimula-tion(taVNS)on preoperative anxiety and sleep quality in patients undergoing laparoscopic myomecto-my.Methods A total of 106 patients scheduled for elective laparoscopic myomectomy were randomly divided into active stimulation group(a-taVNS group,n=53)and sham stimulation group(s-taVNS group,n=53).Trait Anxiety Inventory(TAI)scores,State Anxiety Inventory(SAI)scores,Hos-pital Anxiety and Depression Scale-anxiety(HADS-A)scores,Amsterdam Preoperative Anxiety and Information Scale-anxiety(APAISa)scores,Athens Insomnia Scale(AIS)scores,hemodynamic parameters,and adverse reactions were evaluated before intervention(T0),30 min after interven-tion(T1),and the next morning(T2).The degrees of anxiety improvement(△SAI=SAIT0-SAIT1;△HADS-A=HADS-AT0-HADS-AT1;△APAISa=APAISaT0-APAISaT1)and sleep improvement(△AIS=AIST0-AIST2)were calculated,and their correlations were assessed.Results At T0,there were no significant differences in SAI,HADS-A,and APAISa scores between the two groups(P=0.376,0.682,0.144).At T1,there were significant differences in SAI and HADS-A scores between the two groups(adjusted P＜0.05),while there was no significant difference in APAISa scores(P=0.141).Compared with the s-taVNS group,the a-taVNS group had higher improvement values of △SAI,△HADS-A,and △APAISa(P＜0.001).Compared with T0,the AIS score de-creased and the incidence of sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).Compared with the s-taVNS group,the AIS score and the proportion of patients with sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).There was a positive correlation between the de-gree of anxiety improvement and the degree of sleep improvement in the a-taVNS group(P＜0.05),while there was no significant correlation in the s-taVNS group(P＞0.05).Compared with T0,sys-tolic blood pressure,diastolic blood pressure,and heart rate decreased at T1 in both groups,but there were no significant differences in these parameters between the two groups(P＞0.05).During the study period,no adverse events such as tinnitus,dizziness,headache,nausea,vomiting,or fa-cial flushing occurred in either group.Conclusion The method taVNS can improve preoperative anxiety and reduce the incidence of sleep disorders in patients undergoing laparoscopic myomectomy.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objective:To investigate the correlation between the ratio of apolipoprotein B to apolipoprotein A-I (ApoB/ApoA-I) and unstable carotid plaque in a neurologically healthy population receiving health check-ups.Methods:This cross-sectional study consecutively enrolled 1 149 neurologically healthy individuals who underwent physical examinations at the Health Management Centre of Beijing Tiantan Hospital, Capital Medical University, from October 2021 to September 2022. All eligible participants completed standardized questionnaires, physical examinations and laboratory tests. Laboratory tests of lipid metabolism-related biomarkers included total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), ApoA-I, and ApoB; non-high-density lipoprotein cholesterol and the ApoB/ApoA-I ratio were subsequently calculated. The carotid plaque stability was evaluated using superb microvascular imaging technology. The participants were classified into unstable plaque group (341 cases) and stable plaque group (808 cases) according to the presence or absence of intraplaque neovascularization. The univariate and multivariate logistic regression analyses were used to explore the correlation between the ApoB/ApoA-I ratio and unstable carotid plaques.Results:The study enrolled 1 149 participants totally, with a median age of 57 (49-63) years, including 771 males (67.10%) and 378 females (32.90%), and 341 cases (29.68%) were found with unstable carotid plaques. The unstable plaque group had a higher proportion of males, smoking history, diabetes history, along with higher waist-to-hip ratio and ApoB/ApoA-I ratio compared to the stable plaque group [76.54% vs 63.12%, 33.43% vs 22.77%, 19.06% vs 13.37%, 0.91 (0.85, 0.94) vs 0.89 (0.84, 0.93), 0.64 (0.51, 0.76) vs 0.59 (0.48, 0.72)], while HDL-C and ApoA-I levels were lower [1.39 (1.19, 1.63) vs 1.44 (1.24, 1.66) mmol/L, 1.43 (1.29, 1.60) vs 1.51 (1.36, 1.68) g/L] (all P<0.05). An elevated ApoB/ApoA-I ratio was positively associated with the risk of unstable carotid plaque ( OR=1.61, 95% CI: 1.13-2.29, P=0.008; P for trend<0.001). After adjusting for age, gender, waist-to-hip ratio, history of hypertension, history of diabetes, dyslipidemia, cardiovascular disease, history of smoking and estimated glomerular filtration rate, the positive association between elevated ApoB/ApoA-I ratio and the risk of unstable carotid plaque remained significant ( OR=1.48, 95% CI: 1.01-2.16, P=0.044; P for trend=0.004). Conclusion:In a neurologically healthy population receiving health check-ups, an elevated ApoB/ApoA-I ratio may increase the risk of unstable carotid plaque.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Objective:To explore the factors affecting and improvement recommendations about the congealing temperature of benzyl benzoate as pharmaceutical excipient by the method in the Chinese pharmacopoeia.Methods:The influence of seven factors such as measuring device,sample size,melting temperature,condensation tempera-ture,stop stirring time,stirring frequency and reading of congealing temperature on the determination of congealing temperature of benzyl benzoate was investigated.Results:The key factor for determination of benzyl benzoate con-gealing temperature was the stop stirring time,which was more reasonable when the sample temperature drops to constant or starts to rise slightly was reasonable.Conclusion:The improved method has better accuracy and repeat-ability,and is suitable for the measuring the congealing temperature of pharmaceutical excipient benzyl benzoate.