Objective To investigate the effects of harmine(HM)on the expression level of mitochondrion fusion related proteins and mitochondrial function injury in PC 12 cells.Methods PC 12 cells were divided into cell control group,HM group,mitochondrion mitosis inhibitor Mdivi-1 group,HM+Mdivi-1 group,mitochondrion fission agonist WY14643 group,HM+WY14643 group,with drug concentrations of 1,10,25,50,100 μmol·L-1.After 24 h treatment,the MTT method was used to detect the cell survival rate,and a microscope was used to observe the cell morphology,MitoTracker Red probe staining was used to observe the mitochondrial morphology and the length ratio of vertical and horizontal axes,JC-1 staining was used to detect the mitochondrial membrane potential,and a kit was used to detect ATP level and lactate dehydrogenase(LDH)activity.Immunofluorescence staining and Western blotting were used to assess the expression levels of caspase-3,apoptosis-promoting protein(Bax)cytochrome C(cyt-c),mitochondrial fusion protein(Mfn2)and mitochondrial mitotic protein(Drp-1).The interference sequence of Drp1 was transfected by electroporation,and the siRNA sequence with good transfection effect was screened.The related indicators were detected by fluorescence method,MTT method,and immunoblotting method in cooperation with drug intervention.Results MTT results showed that compared with the cell control group,the survival rate of HM group,Mdivi-1 group,HM+Mdivi-1 group,WY14643 group and HM+WY14643 group decreased significantly(P＜0.01),and the EC50 were(11.48±2.32),(12.35±1.67),(14.88±2.07),(39.14±3.25),(20.09±1.97),respectively.According to this,subsequent experiments selected 20 μmol·L-1for HM,WY 14643 and HM+WY14643 as working concentrations to construct PC 12 cell model.Microscopic observation and MitoTracker Red probe staining showed that the cell density in the drug group decreased in varying degrees,and a transition from branched to round morphology in the drug-treated groups was observed.The morphology of mitochondria tended to be round,and the ratio of the length of the longitudinal axis to transverse axis was(3.33±0.72)in the cell control group,(2.19±0.58)in the HM group,(2.45±0.44)in Mdivi-1 group,and(1.43±0.62)in HM+Mdivi-1 group,respectively.The results of JC-1 staining showed that compared with the cell control group,the mitochondrial mode potential of the HM group significantly decreased(P＜0.01).ROS significantly increased(P＜0.01)and ATP levels decreased(P＜0.01),and LDH enzyme activity increased(P＜0.01).Immunofluorescence staining and Western blotting results showed that compared with the cell control group,the expression levels of proapoptotic proteins Bax,cytochrome C,and caspase-3 in the HM group were significantly increased(all P＜0.01).Compared with the cell control group,the expression level of mitochondrial fission related protein Drp1 in HM group was significantly higher(P＜0.01).The expression level of mitochondrial fusion related protein Mfn2 significantly decreased(P＜0.01).After specific interference with Drp1 and synergistic intervention with HM,the survival rate of PC 12 cells in each interference group decreased compared to each drug intervention group.The expression of Drp1 and Mfn2 was downregulated,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion HM can reduce the mitochoudrial membrane potential and ATP levels by accumulating ROS,there by activating the caspase-3 apoptosis pathway and promoting cell apoptosis.Mitochondrial fusion division may be involved in the damage of PC12 cells caused by HM,initiating apoptosis through the mitochondrial pathway.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective:To investigate the association between body mass index (BMI) and the risk of chronic obstructive pulmonary disease (COPD).Methods:This study employed a single-center, cross-sectional design combined with online Mendelian randomization (MR) analysis. A total of 16 187 pieces of lung function data for COPD screening from the “Happy Breathing” project in the Jingzhou area between September 2021 and October 2023 were initially collected. Cases with missing questionnaire information, failed quality control, or isolated restrictive or small airway dysfunction were excluded, resulting in a final dataset of 3 999 cases, comprising 2 330 non-COPD and 1 669 COPD cases. Binary COPD status was set as the outcome variable, with BMI as the exposure variable. A smooth curve plot was used to depict the relationship between BMI and COPD prevalence; if non-linearity was observed, a two-piece linear regression model was employed to calculate threshold effects, adjusting for potential confounders such as age, sex, smoking history, biomass fuel exposure, and COPD awareness. Subsequently, online genome-wide association study (GWAS) data were utilized for MR analysis to explore any potential causal link between high BMI and COPD development.Results:Analysis of the “Happy Breathing” COPD screening data from the Jingzhou area revealed a nonlinear relationship between BMI and COPD risk. For BMI values <23.7 kg/m2, each 1 kg/m2 increase in BMI was associated with an 18% decrease in COPD risk ( OR=0.82, 95% CI: 0.79-0.85). However, for BMI >23.7 kg/m2, no significant association was found between increasing BMI and COPD risk ( OR=1.00, 95% CI: 0.96-1.05). MR analysis using online GWAS data suggested no potential causal relationship between high BMI and COPD occurrence, with both heterogeneity and pleiotropy tests yielding P>0.05. Conclusion:There may be a nonlinear relationship between BMI and the risk of COPD, with no apparent association between BMI and COPD risk for values above 23.7 kg/m2.

Objective:To investigate the effects of 3-methyladenine(3-MA)on extracellular matrix deposition in early diabetic nephropathy(DN)and its mechanism.Methods:A streptozotocin(STZ)-induced type 1 diabetes mouse model was used, and the mice were divided into vehicle control group, diabetes group(STZ group), 3-MA group, and chloroquine(CQ)group, 8 mice in each group. After 6 weeks of intervention, both kidneys were harvested, and the kidney-to-body weight ratio was recorded. Western blotting was performed to detect protein expressions of renal cortex fibronectin, α-smooth muscle actin(α-SMA), LC3, Beclin 1, p62, and vascular endothelial growth factor(VEGF). Immunohistochemistry was used to observe kidney fibronectin staining. Bioinformatics analysis was conducted on shared genes between diabetic nephropathy(DN)gene targets and 3-MA predicted gene targets.Results:Both 3-MA and CQ exhibited certain hypoglycemic effects in diabetic mice. Compared to the STZ group, the kidney-to-body weight ratio decreased in the 3-MA group( P<0.05). Western blotting showed that 3-MA reduced the expression of renal cortex matrix-related proteins fibronectin and α-SMA in diabetic mice( P<0.05 or P<0.01). Immunohistochemistry also revealed that 3-MA reduced fibronectin staining in the kidneys of diabetic mice. Both 3-MA and CQ inhibited the protein expression of renal cortex Beclin 1 in diabetic mice(both P<0.05), while 3-MA increased the expression of renal cortex p62( P<0.05). Bioinformatics analysis indicated a connection between shared genes of DN gene targets and 3-MA predicted gene targets with the VEGF signaling pathway. Western blotting results further showed that 3-MA reduced renal cortex VEGF expression in diabetic mice( P<0.01). Conclusion:3-MA can alleviate extracellular matrix deposition in the kidneys of early DN mice by inhibiting the VEGF signaling pathway.

This article reviews the clinical studies about the treatment of allergic rhinitis （AR） with traditional Chinese medicine （TCM） in recent years. AR is a common and frequently occurring disease in the department of otolaryngology. The common manifestations of AR include nasal congestion， sneezing， runny nose， and nasal itching. AR， belonging to the category of rhinitis， is a dominant disease in the TCM treatment of otorhinolaryngologic diseases and head and neck diseases. The ancient literature has laid a solid theoretical basis on the etiology and pathogenesis of AR. According to the ancient literature， the theoretical basis， and their own experience， modern doctors classified the causes of AR into the disorders in Zang-fu organs and six meridians. Most of the explanations focus on the disorders in Zang-fu organs， especially the lung， spleen， and kidney. The clinical studies in this field mainly involve TCM treatment alone， integrated TCM and Western medicine treatment， and TCM external treatment. These therapies have good efficacy in the clinical treatment of AR. Among them， TCM treatment alone has significant advantages in alleviating the symptoms and nasal signs， declining the scores of related scales， and reducing the eosinophil count （EOS） of nasal secretions， with definite long-term efficacy. Integrated TCM and Western medicine treatment can complement with each other. The TCM external treatment methods include acupuncture， moxibustion， acupoint catgut embedding， acupoint application， and nasal irrigation with TCM， which are safe， simple， acceptable by patients and have good therapeutic effect. Finally， the clinical research status of TCM treatment of AR was summarized， and suggestions were put forward from three aspects： standardizing the clinical research protocol of TCM， encouraging pure TCM research， and exploring the mechanism of TCM treatment on the basis of frontier research achievements. This review aims to provide higher-level evidence for subsequent clinical research and promote the research on dominant AR diseases.

Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.

Objective:To observe the effect of Tuina(Chinese therapeutic massage)combined with functional training in improving clinical symptoms and balance function in patients with meniscus injury. Methods:A total of 93 patients with grade Ⅰ-Ⅱ meniscus injury were randomly divided into a functional training group,a Tuina group,and a combination group,with 31 cases in each group.The Tuina group received Tuina manipulation.The functional training group underwent functional training under the supervision of physicians.The combination group received Tuina manipulation in addition to the functional training.The treatment course of all three groups was 8 weeks.The clinical symptoms were observed before the intervention and after 4 and 8 weeks of interventions,and the changes in knee injury and osteoarthritis outcome score(KOOS)and Y-balance test(YBT)were compared. Results:There was no statistically significant difference in the total response rate among the three groups after treatment(P>0.05).The total and subscale KOOS in the three groups were significantly higher than those before treatment after 4 and 8 weeks of interventions(P<0.05).There was a statistically significant difference in the total KOOS between the combination group and the functional training group after 4 and 8 weeks of interventions(P<0.05);there was a statistically significant difference in the score of daily living ability and sports and recreation function between the two groups after 8 weeks of interventions(P<0.05).The YBT balance coefficients of the affected and non-affected knees of the three groups were significantly improved after 4 and 8 weeks of interventions(P<0.05),and there was no statistically significant difference among the groups(P>0.05). Conclusion:Tuina,functional training,and their combination can improve clinical symptoms and balance function in patients with grade Ⅰ-Ⅱ meniscus injury.Tuina combined with functional training is significantly effective in improving daily living ability and sports and recreation function.

Objective: To evaluate the efficacy of Tuina (Chinese therapeutic massage) manipulation plus horse-riding squat exercise in treating knee osteoarthritis (KOA) and optimize the combining protocol. Methods: Based on a 2×2 factorial design, 120 eligible KOA patients were randomized into a manipulation group (group A1B2), a manipulation plus horse-riding squat group (group A1B1), a sitting knee-adjustment group (group A2B2 group), and a sitting knee-adjustment plus horse-riding squat group (group A2B1), with 30 cases in each group. The intervention was conducted three times a week, lasting for four weeks. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was taken as the major measure for efficacy evaluation (including three component scores, pain, stiffness, and daily function, and total score). Results: The three component scores (pain, stiffness, and daily function) and the total score of WOMAC showed significant differences after the intervention in the four groups (P<0.05). There were significant inter-group differences in the WOMAC stiffness score amongst the four groups after the intervention (P<0.05). In group A1B1, the step length, stride, walking speed, and knee joint flexion angle changed significantly after treatment (P<0.05). After the intervention, the step length changed significantly in group A1B2 (P<0.05), and the walking speed changed significantly in group A2B1 (P<0.05). There were no significant differences in the step length, stride, walking speed, or knee joint flexion angle among the four groups (P>0.05). The extensor peak torque at 180 °/s changed significantly in group A1B2 after treatment (P<0.05). Neither the intra-group nor the inter-group comparisons of the four groups revealed significant differences in the other isokinetic muscle strength parameters (P>0.05). The main effect of manipulation showed significant in affecting the WOMAC pain and total scores (P<0.05). The main effect of horse-riding squat exercise showed significant in affecting the WOMAC pain and stiffness scores (P<0.05). Conclusion: The four treatment protocols all can improve the symptoms of KOA, for instance, relieving pain and stiffness, and enhancing daily function. Group A2B1 produces the most eminent effect in relieving joint stiffness. The main effects of both manipulation and horse-riding squat exercise are significant in reducing pain. Besides, the main effect of horse-riding squat exercise is significant in relieving joint stiffness.

Speech expression is an important high-level cognitive behavior of human beings. The realization of this behavior is closely related to human brain activity. Both true speech expression and speech imagination can activate part of the same brain area. Therefore, speech imagery becomes a new paradigm of brain-computer interaction. Brain-computer interface (BCI) based on speech imagery has the advantages of spontaneous generation, no training, and friendliness to subjects, so it has attracted the attention of many scholars. However, this interactive technology is not mature in the design of experimental paradigms and the choice of imagination materials, and there are many issues that need to be discussed urgently. Therefore, in response to these problems, this article first expounds the neural mechanism of speech imagery. Then, by reviewing the previous BCI research of speech imagery, the mainstream methods and core technologies of experimental paradigm, imagination materials, data processing and so on are systematically analyzed. Finally, the key problems and main challenges that restrict the development of this type of BCI are discussed. And the future development and application perspective of the speech imaginary BCI system are prospected.
Brain ; Computers ; Humans ; Imagery, Psychotherapy ; Speech ; Technology

Objective:To evaluate the effects of smart stethoscope on the monitoring childhood asthma exacerbation, so as to assist family management in childhood asthma.Methods:A prospective randomized controlled study was carried out.A total of 80 children with asthma who were treated at Department of Pediatric Respiratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Tonxin Pediatric Clinic from November 2020 to May 2021 were enrolled and randomly divided into a test group of 40 cases (used the smart stethoscope) and a control group of 40 cases(not used the smart stethoscope). Medical history data were collected.The control group received monthly routine follow-up, while the test group was followed up both routinely and by smart stethoscope.In the test group, hearing wheezing sound was regarded as asthma exacerbation, and in the control group, the asthma exacerbation was reported by the parents themselves.The frequency of asthma exacerbation, asthma control level and quality of life were compared between the two groups.The recognition, diagnosis, treatment and outcomes of acute asthma exacerbation in two groups of children were described and analyzed.Measurement data were analyzed by t test or Mann- Whitney U test.Numeration data were analyzed by χ2 test. Results:Respiratory sounds collected by smart stethoscope in the test group were assessed by 3 specialist physicians.There were 12 wheezing rales (42.86%), 1 moist rale (3.57%) and 1 rhonchi rale (3.57%). Besides, 12 files (42.86%) were difficult to distinguish, and 2 files (7.14%) induced inconsistent identification.The number of asthma exacerbation was 12 in the test group and 5 in the control group.In the test group, 12 were recognized by the smart stethoscope, and only 6 were recognized by the parents.Comparing the diagnosis and treatment measures between two groups, it was found that there were more children in the test group (38.1%) receiving home treatment through telemedicine than those in the control group (20.0%). Besides, there were less children (61.9%) in the test group receiving unplanned hospital treatment (including unplanned outpatient, emergency and hospitalization) than those in the control group (80.0%). There was no statistically significant difference between the two groups of children during acute asthma exacerbation ( χ2=4.67, P=0.097). Parents were satisfied with the common functions, convenience and stability of smart stethoscope. Conclusions:Smart stethoscope can acquire the respiratory sounds of children with asthma in real time, achieving timely detection, diagnosis and treatment of asthma exacerbation in children.What′s more, smart stethoscope reduces the incidence of unplanned hospital diagnosis and treatment, and assists parents with better family management of children asthma.