OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVE: To investigate the clinical efficacy of Zhuangdan Yanshi Decoction combined with dapoxetine hydrochloride in the treatment of premature ejaculation with cholestasis and phlegm disturbance. METHODS: A total of 120 patients diagnosed with premature ejaculation and treated in the Andrology Outpatient Department of Shaanxi Provincial Hospital of Traditional Chinese Medicine from March to December in 2022 were selected and randomly divided into treatment group and control group, with 60 cases in each group. The incubation period of intravaginal ejaculation (IELT), the Diagnostic Scale of Premature Ejaculation (PEDT), the Premature Ejaculation Assessment Scale (PEP), the 5-item Sexual Function Evaluation of Chinese Premature Ejaculation Patients (CIPE-5) and the improvement of traditional Chinese medicine symptom scores were compared before and after the treatment. And the adverse reactions were recorded as well. RESULTS: A total of 105 cases were ultimately included, with 55 cases in the treatment group and 50 cases in the control group. Measurable improvements in IELT, PEDT scores, PEP scores, CIPE scores and TCM symptom scores had been found after treatment in both of two groups (P<0.05). Moreover, the improvement in the treatment group was superior to that in the control group (P<0.05). The total effective rate in the treatment group was 89.1%, which was higher than that(84%) in the control group, with no statistically significant difference between the two groups (P>0.05). The incidence of adverse reactions in the treatment group was 9.1%, which was 24% in the control group. There was significantly difference between two groups (P<0.05). CONCLUSION The combination therapy with Zhuangdan Yanshi Decoction and dapoxetine hydrochloride for premature ejaculation associated with cholestasis and phlegm disturbance syndrome is definite, and it can reduce the side effects of drugs, which is better than oral dapoxetine hydrochloride alone.
Humans ; Premature Ejaculation/drug therapy* ; Benzylamines/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Naphthalenes/therapeutic use* ; Cholestasis/complications* ; Adult ; Benzyl Compounds/therapeutic use* ; Medicine, Chinese Traditional ; Treatment Outcome

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective:To assess the expression level and clinical significance of interleukin-17A(IL-17A) in restenosis after endoluminal treatment of lower extremity atherosclerotic occlusive (LEASO).Methods:Using retrospective analysis, 252 LEASO patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from April 2021 to October 2023 were selected; 20 patients were lost to follow-up and 232 patients were enrolled. The patients underwent endoluminal intervention(balloon dilatation/stent placement) after admission, and they were divided into the restenosis group ( n=52) and the non-stenosis group ( n=180) according to the occurrence of restenosis during the follow-up period. Gender, age, body mass index, history of hypertension, history of diabetes mellitus, history of smoking, history of coronary artery disease, surgically diseased limb, C-reactive protein, total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose, and length of vascular occlusion were recorded and compared between the two groups. Serum IL-17A expression levels were measured in the enrolled patients preoperatively, 24 h postoperatively, 1 month postoperatively, 3 months postoperatively, and 6 months postoperatively. Univariate and multivariate Logistic regression analyses were used to evaluate the preoperative clinical data of patients in the restenosis group and non-restenosis group, and to investigate the risk factors affecting the occurrence of restenosis in patients. Immunohistochemistry was applied to determine the expression level of IL-17A in the plaque tissues of the restenosis group and the non-stenosis group, and to assess the predictive value of IL-17A for restenosis after endoluminal therapy in patients with LEASO. Measurement data with normal distribution were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; measurement data with skewed distribution were expressed as median (interquartile range) [ M( Q1, Q3)], and Mann-Whitney U-test was used for comparison between groups; and count data were expressed as the number of cases and percentage, and Chi-square test was used for comparison between groups; comparisons between the two groups with multiple time-point indicators were performed using repeated-measures data ANOVA. Factors associated with the occurrence of postoperative restenosis in LEASO patients were assessed using univariate and multivariate Logistic regression analyses. Risk prediction efficacy analysis was performed using receiver operating characteristic (ROC) curves. The correlation between IL-17A expression and the degree of restenosis was analysed using the Spearman method. Results:The relative expression level of IL-17A in the serum of patients in the restenosis group was higher than that in the non-stenosis group, and showed an increasing trend in patients with moderate-to-severe stenosis and complete occlusion. The results of the immunohistochemical method showed that the rate of IL-17A-positive cells and the intensity of staining in the plaque tissues of patients in the restenosis group were higher than those in the non-stenosis group ( P< 0.01), and the composite score of the positive rate×intensity of staining in the restenosis group was 6.7 (5.0, 8.0), and that in the non-stenosis group was 2.1 (1.0, 3.0). The expression level of IL-17A in the plaque tissue of the restenosis group was positively correlated with the degree of stenosis ( r= 0.76, P< 0.001). The results of the ROC curve analysis showed that predictive value of IL-17A for restenosis after LEASO intervention was high. Conclusions:IL-17A may play an important role in postoperative restenosis in LEASO patients by promoting inflammation response. It provides a new detection index for the early prediction of restenosis after LEASO intervention.

Objective:To analyze the positioning error and the overall setup errors (OSEs) of patients undergoing gamma knife pain-free face mask fractionated treatment for head tumors based on kV orthogonal image guidance.Methods:A total of 58 patients who received image-guided fractionated gamma knife treatment for head tumors with a pain-free face mask at the Gamma Knife Treatment Center of Xi'an International Medical Center Hospital from July 1, 2022 to May 31, 2024 were included in the study. A kV-class orthogonal X-ray IGPS image-guided positioning system was used to collect positioning errors in three translational directions: left-right (X), anterior-posterior (Y), and head-foot (Z), as well as in three rotational directions: left-right (P), anterior-posterior (R), and head-foot ( Y) before correction. After online correction and combined with manual positioning verification, the corrected positioning errors were recalculated. The OSEs in translational and rotational directions were calculated before and after correction. The positioning errors in all six directions (X, Y, Z, P, R, Y) before and after correction were plotted. And the OSE scatter plots in translational and rotational directions were created accordingly. Errors in the six directions and OSEs in translational and rotational directions were compared. The OSEs in translational and rotational directions were analyzed across different age groups and genders. Results:The pre-correction positioning errors in the X, Y, Z, P, R, Y directions for patients were (0.45±1.54) mm, -0.96 (-1.70, -0.28) mm, 1.67 (-0.15, 3.07) mm, (0.70±1.60) °, 0.65 (0.30, 1.19) °, (0.59±0.87) °, and the post-correction positioning errors were (-0.02±0.18) mm, 0.15 (0.10, 0.21) mm, 0.06 (-0.04, 0.16) mm, (0.20±0.79) °, 0.42 (0.19, 0.78) °, (0.20±0.63) °. There were statistically significant differences between before and after correction ( t=2.30, P=0.025; Z=-5.43, P<0.001; Z=-4.10, P<0.001; t=2.56, P=0.013; Z=-3.21, P=0.001; t=3.21, P=0.002). The OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before correction were 3.07 (1.93, 4.35) mm, 1.90 (1.28, 2.66) °, and the OSEs after correction were 0.27 (0.21, 0.33) mm, 1.08 (0.70, 1.54) °, with statistically significant differences ( Z=-6.60, P<0.001; Z=-5.52, P<0.001). For patients aged 18-44 years, the OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before and after correction were 3.65 (1.62, 3.95), 0.21 (0.21, 0.31) mm, 3.25 (2.24, 3.96) °, 0.92 (0.59, 1.45) °; for patients aged 45-59 years, the OSEs were 3.57 (2.17, 5.22), 0.29 (0.22, 0.35) mm, 1.89 (1.30, 2.30) °, 1.08 (0.62, 1.51) °; for patients aged 60-74 years, the OSEs were 2.92 (1.74, 4.06), 0.24 (0.19, 0.35) mm, 2.16 (1.09, 2.95) °, 0.98 (0.78, 1.75) °; for patients aged 75-89 years, the OSEs were 3.24 (2.12, 4.37), 0.29 (0.22, 0.47) mm, 1.73 (1.01, 1.83) °, 0.60 (0.47, 1.51) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction among the four age groups ( H=1.23, P=0.747; H=1.74, P=0.627; H=7.45, P=0.059; H=2.80, P=0.424). For male patients, the OSEs before and after correction in translational (X, Y, Z) and rotational (P, R, Y) directions were (3.19±1.59), 0.27 (0.27, 0.33) mm, 1.89 (1.27, 2.75) °, (0.84±0.59) °; for female patients, the OSEs were (3.22±1.99), 0.26 (0.25, 0.35) mm, 1.90 (1.34, 2.41) °, (1.04±0.46) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction between genders ( t=-0.07, P=0.949; Z=-0.48, P=0.632; Z=-0.02, P=0.161; t=-2.80, P=0.424) . Conclusions:The image-guided system, which is based on the kV orthogonal X-ray stereoscopic imaging, can significantly reduce the positioning errors between fractions of pain-free face mask gamma knife treatment for head tumor patients and improve the positioning accuracy of the gamma knife through the dual verification process of "automatic correction and manual review".

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.