Objective: To explore the interaction between school bullying and insomnia in relation to depression-anxiety-stress emotions among primary and secondary school students,so as to provide a basis for preventing negative emotional states in adolescents. Methods: In October 2024, a stratified cluster sampling method was used to select 3 058 students in grade 5-6 of primary, junior and senior high school in Sheyang County of Jiangsu Province. The Delaware Bullying Victimization Scale, Insomnia Severity Index, Depression-Anxiety-Stress Scale-21, and Study Condition Questionnaire were employed to investigate school bullying, insomnia, depression-anxiety-stress emotions, and academic performance. The χ 2 test and Logistic regression were used to analyze the association between school bullying and insomnia interactions and depression-anxiety-stress emotions among primary and secondary school students, multiplicative interaction analysis was conducted, and additive interaction analysis was performed using R software. Results: The detection rates of depression-anxiety-stress emotions among primary and secondary school students were 21.6%, 28.4% and 10.8%, respectively. The detection rates of physical bullying, relationship bullying, verbal bullying and cyberbullying in school bullying were 10.6%, 14.0%, 22.3%, and 6.2%, respectively. The detection rate for insomnia was 23.1%. Results from Logistic regression analysis showed that, after adjusting for relevant factors, physical, relational, verbal, and cyberbullying and insomnia were positively correlated with the detection rates of depression ( OR = 5.72- 10.93), anxiety ( OR =6.35-12.17), and stress emotions ( OR =5.97-14.52) among primary and secondary school students (all P <0.01). The multiplicative interaction between physical, relational, verbal, and cyberbullying and insomnia was positively correlated with the detection rates of depression ( OR =8.00-18.01), anxiety ( OR =11.35-17.76), and stress emotions ( OR =7.64-9.12) in primary and secondary school students (all P <0.01). Additive interactions were observed between physical, relational, verbal, and cyberbullying and insomnia in relation to the detection rates of depression, anxiety, and stress emotions among primary and secondary school students (both RERI and AP >0 and the credible interval excluded 0, SI >1 and the credible interval excluded 1). Conclusion School bullying and insomnia are associated with depression, anxiety, and stress emotions among primary and secondary school students, and they exhibit both multiplicative and additive interactions.

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

OBJECTIVE: To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS: According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS: The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.
Humans ; Male ; Tadalafil ; Erectile Dysfunction/etiology* ; Moxibustion ; Middle Aged ; Prospective Studies ; Adult ; Carbolines/administration & dosage* ; Diabetes Complications/therapy* ; Aged ; Treatment Outcome ; Combined Modality Therapy

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.