Objective: To evaluate the implementation process of a school-family collaborative "online+offline" tobacco control intervention program in junior high school in Beijing and to explore the execution status, influencing factors and sustainability potential of the intervention, so as to provide evidence for optimizing youth tobacco control strategies. Methods: In November 2024, using the random number table method, four first year junior high school classes were selected from three schools each in Fengtai District, Tongzhou District, and Fangshan District of Beijing. One class served as the control group, while the other three classes were designated as intervention groups (one each for online intervention, offline intervention, and combined online offline intervention). The control group received only conventional education.The online intervention group was engaged in WeChat push interventions, including watching micro videos, viewing promotional materials, participating in online quizzes and mini games; the offline intervention group attended knowledge lectures, played peer games, and participated in offline knowledge competitions; the combined online offline intervention group integrated all the aforementioned online and offline intervention measures. The intervention period was from November 2024 to June 2025, spanning a total of 7 months. Based on the Practical, Robust Implementation and Sustainability Model(PRISM) framework, a qualitative research design was employed to conduct semi structured interviews with 48 participants (12 in each of the intervention groups and 12 organizational staff members) from the Centers for Disease Control and Prevention (CDC) in 3 districts and 3 sampled schools. The interview outlines were designed according to the intervention plan. Data was managed using Nvivo 12.0 software and analyzed following Colaizzi s seven step phenomenological analysis method. Theoretical saturation was assessed using a reserved subset of transcripts. Results: Four core themes were identified in the tobacco control intervention process. Overall fidelity of intervention implementation was largely consistent with the original plan, and students showed strong willingness and positive evaluations toward interactive formats such as knowledge contests and peer games, though occasional breakdowns in school-family communication and blurred boundaries between online and offline components were observed; the participants showed a polarized response in terms of satisfaction and participation, most students and parents recognized the significance of the activity, and some parents observed a reduction in smoking behavior; the implementation of internal tobacco control policies in the school was strict, and the atmosphere was favorable, but there was still room for improvement, such as the scarcity of community tobacco control activities and the difficulty in implementing smoke free units; implementation and sustainability infrastructure were preliminarily established, such as through homeroom teacher supervision and training student assistants to assisted in activities, while the sustainability support system required further refinement. Conclusion The school-family collaborative "online+offline" tobacco control intervention has demonstrated significant positive effects, but further optimization of activity design, enhancement of community reward mechanisms, and standardized training are required to improve the efficacy and sustainability of the intervention.

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To investigate the effect of programmed cell death-ligand 1(PD-L1)monoclonal antibody and paclitaxel(PTX)combined with lentinan(LNT)on human breast cancer MDA-MB-231 cells in vitro.Methods MDA-MB-231 cells,human peripheral blood mononuclear cells(PBMCs),and MDA-MB-231+PBMCs co-culture were randomly divided into control group,PTX group,LNT group,MPDL3280A(PD-L1 monoclonal antibody)group,PTX+LNT group,and PTX+LNT+MPDL3280A group.The cell activity was detected by CCK8.The expressions of MHC-I and PD-L1 were detected by flow cytometry.The levels of IFN-γ and TNF-α were detected by ELISA kits.Results Compared with control group,the activity of MDA-MB-231 cells was significant inhibited in PTX group,MPDL3280A group,PTX+LNT group,and PTX+LNT+MPDL3280A group(P＜0.01).LNT group and PTX+LNT+MPDL3280A group significantly promoted the immune effect of PBMCs(P＜0.05,P＜0.01).PTX+LNT+MPDL3280A group significantly inhibited the activity of MDA-MB-231cells co-cultured with PBMCs(0.56±0.16 vs.0.39±0.13,P＜0.05).Compared with the negative control,LNT significantly promoted the expression of PD-L1 in MDA-MB-231 and the secretion of IFN-γ by PBMCs(P＜0.05).Conclusion By blocking the effect between PD-L1 and PD-1,PD-L1 monoclonal antibody can improve immunity and promote the antitumor effect of PTX combined with LNT in vitro.

Objective:To investigate the clinicopathological features of advanced-stage mycosis fungoides (MF).Methods:A retrospective case-series study was conducted. The clinical data of 5 cases diagnosed with advanced-stage MF in Chengdu Second People's Hospital between January 2015 and July 2023 were analyzed. The clinicopathological features of patients were summarized.Results:There were 2 males and 3 females in 5 MF patients, with the median age of 55 years (45-86 years) and the medical history of 2-16 years. The main symptoms were pruritus and erythema. The lesions were presented by erythema, scales, plaques, blisters, erosion, ulcers, pigmentation, nodules, and erythroderma. Histopathological examination showed different skin lesion patterns such as psoriasis-like, interfacial dermatitis, non-infectious granuloma, deep and shallow perivascular dermatitis, tumors. Among 5 patients, 1 case was mycosis fungoides bullosa, 2 cases were erythrodermic MF, 1 case was granulomatous MF, and 1 case was classical MF. Lymphocyte epidermis was found in 4 cases, cytoplasmic halos cells lined up along the basal layer of the epidermis and Pautrier microabscess were found in 3 cases, large-cell transformation was found in 1 case. Tumor cells were positive for CD3, CD4 and negative for CD8, CD56, ALK and CD20; EBER 1/2 hybridization in situ was negative. CD30 was positive in transformed large cells and T cell receptor gene rearrangement was positive. The tumor cells were detected in bone marrow and peripheral blood of 2 cases and in cerebrospinal fluid of 1 case. Head magnetic resonance imaging of 1 case indicated abnormal signal nodules in the right temporal region and the normal architecture of the lymph nodes in 2 cases was completed destroyed by malignant cells. TNMB stage: 2 cases were in stage Ⅱ B, 2 cases were in stage Ⅳ A2, and 1 case was in stage Ⅳ B. Interferon α-based systemic therapy was performed in 1 case, 2 cases received chemotherapy or combined with intrathecal injection and radiotherapy, and other 2 cases were not treated. All of them just achieved partial remission. Finally, 1 case died of sudden cardiac death, 2 cases died of lung infection, and 2 cases survived with tumors. Conclusions:Advanced-stage MF is presented with different skin lesion manifestations and histopathologic changes. Multidisciplinary combined management helps the diagnosis and treatment of MF.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To investigate the effect of programmed cell death-ligand 1(PD-L1)monoclonal antibody and paclitaxel(PTX)combined with lentinan(LNT)on human breast cancer MDA-MB-231 cells in vitro.Methods MDA-MB-231 cells,human peripheral blood mononuclear cells(PBMCs),and MDA-MB-231+PBMCs co-culture were randomly divided into control group,PTX group,LNT group,MPDL3280A(PD-L1 monoclonal antibody)group,PTX+LNT group,and PTX+LNT+MPDL3280A group.The cell activity was detected by CCK8.The expressions of MHC-I and PD-L1 were detected by flow cytometry.The levels of IFN-γ and TNF-α were detected by ELISA kits.Results Compared with control group,the activity of MDA-MB-231 cells was significant inhibited in PTX group,MPDL3280A group,PTX+LNT group,and PTX+LNT+MPDL3280A group(P＜0.01).LNT group and PTX+LNT+MPDL3280A group significantly promoted the immune effect of PBMCs(P＜0.05,P＜0.01).PTX+LNT+MPDL3280A group significantly inhibited the activity of MDA-MB-231cells co-cultured with PBMCs(0.56±0.16 vs.0.39±0.13,P＜0.05).Compared with the negative control,LNT significantly promoted the expression of PD-L1 in MDA-MB-231 and the secretion of IFN-γ by PBMCs(P＜0.05).Conclusion By blocking the effect between PD-L1 and PD-1,PD-L1 monoclonal antibody can improve immunity and promote the antitumor effect of PTX combined with LNT in vitro.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.