ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

OBJECTIVE: To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insecticides (NNI). METHODS: Fifteen C57BL/6 male mice were randomly divided into control group (CTRL group), exposure group (NNI group) and Lactobacillus intervention group (NNI-L group). The mice in CTRL group were given 0.02ml/g of 0.5% carboxymethyl cellulose sodium solution by gavage for 14 days. The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days. The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5×108cfu/ml of Lactobacillus reuteri powder solution for 14 days. Then, the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining, immunofluorescence staining and RNA sequencing. RESULTS: Compared with CTRL group, the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner. And the decline in the number of spermatogenic cells and sperm was observed. And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group. The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequencing, with significant down-regulation being found in NPFF and IGF2. While the expression of HSD3B8 was significantly up-regulated. The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri. CONCLUSION Testicular spermatogenesis and endocrine function can be damaged by NNI exposure. And oral administration of Lactobacillus reuteri protects testis from the adverse effects of NNI toxicity.
Animals ; Male ; Limosilactobacillus reuteri ; Testis/pathology* ; Mice ; Mice, Inbred C57BL ; Insecticides/toxicity* ; Neonicotinoids/toxicity* ; Probiotics ; Spermatogenesis/drug effects*

OBJECTIVE: To evaluate the clinical efficacy of "Shibao Decoction" in the management of late-onset hypogonadism (LOH) caused by deficiency of kidney essence. METHODS: Sixty male patients with late-onset hypogonadism of kidney essence deficiency type were randomly assigned to the treatment group and the control group, each with 30 cases. The patients in treatment group were treated with oral Shibao Decoction, while the control group was treated with oral Testosterone Undecanoate Capsules. The patients in both groups were treated for 12 weeks. The PADAM symptom score, TCM syndrome score, serum total testosterone (TT), serum free testosterone (FT), sex hormone binding globulin (SHBG), body mass index (BMI), total skeletal muscle mass index (SMI), appendicular skeletal muscle mass index (ASMI), FBG, FINS, and insulin resistance index (HOMA-IR) levels were compared between the two groups. RESULTS: After treatment, PADAM scores for each item and TCM symptoms score decreased, TT and FT increased in both groups, all with statistically significant differences from those of pre-treatment (P<0.05). The level of SHBG in the control group decreased (P<0.05), which had not changed significantly in the treatment group (P>0.05). After treatment, SMI and ASMI increased in both groups significantly (P<0.05). BMI decreased in the control group (P<0.05), which had not changed significantly in the treatment group (P>0.05). The level of FINS decreased in the control group (P<0.05), which had not changed significantly in the treatment group (P>0.05). FPG had not changed significantly in both groups (P>0.05), and the insulin resistance index (HOMA-IR) had significantly improved in both groups, all with statistically significant differences from those of pre-treatment (P<0.05). After treatment, the total effective rates of PADAM score and TCM syndrome score in the treatment group were 73.3% and 86.6% respectively, and the total effective rates in the control group were 66.7% and 76.6% respectively. The total effective rates of the two scores in the treatment group were slightly higher than those in the control group (P>0.05). There was no significant difference in the indicators between the two groups after treatment, and the treatment group is generally comparable with the control group in the therapeutic effects (P>0.05). And no adverse reactions occurred during treatment in both groups. CONCLUSION The "Shibao Decoction" has a remarkable therapeutic effect on late-onset hypogonadism caused by deficiency of kidney essence and has good safety. It can be used as an alternative to testosterone undecanoate and is worthy of clinical promotion and application.
Humans ; Hypogonadism/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Testosterone/therapeutic use* ; Treatment Outcome ; Sex Hormone-Binding Globulin ; Medicine, Chinese Traditional ; Middle Aged ; Adult ; Kidney

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.