OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

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*

Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists' understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*