BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

Objective To observe the clinical efficacy of the modified Huangan Lipi Decoction(mainly composed of Sclerotium Poriae Pararadicis,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,Polygalae Radix,Acori Tatarinowii Rhizoma,and Curcumae Radix)combined with acupuncture at Sifeng(EX-UE10)points in the treatment of children with tic disorders(TD).Methods Seventy cases of TD children with spleen deficiency and liver hyperactivity syndrome were randomly divided into the treatment group and the control group,with 35 cases in each group.The control group was treated with conventional western medicine of Tiapride Hydrochloride Tablets,while the treatment group was treated with the combination of the modified Huangan Lipi Decoction and acupuncture at Sifeng points.Both groups were treated for 8 weeks.The changes of the Yale Global Tic Severity Scale(YGTSS)item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were observed before and after treatment.Moreover,the clinical efficacy and safety in the two groups were evaluated.Results(1)After 8 weeks of treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 68.57%(24/35).The intergroup comparison showed that the total effective rate(tested by chi-square test)and the overall therapeutic efficacy(tested by rank-sum test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P＜0.05).(2)After treatment,the YGTSS item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were significantly lower than those before treatment(P＜0.01),and the effect on lowering the above scores of the treatment group was significantly superior to that of the control group,the differences being all statistically significant(P＜0.01).(3)During the treatment,the incidence of adverse reactions in the treatment group was 2.86%(1/35)and that in the control group was 8.57%(3/35).The intergroup comparison showed that the incidence of adverse reactions in the treatment group tended to be lower than that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Modified Huangan Lipi Decoction combined with acupuncture at Sifeng points exert certain effect in the treatment of TD children with spleen deficiency and liver hyperactivity syndrome,and its efficacy is superior to that of the western medicine Tiapride Hydrochloride Tablets.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.

Objective To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis(RA)forefoot deformity reconstruction.Methods Retrospective analysis was performed on 50 patients(76 feet)with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019.According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divid-ed into the fifth metatarsal head preservation group(preservation group)and the fifth metatarsal head resection group(resec-tion group).Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of(60.37±8.60)years old;the course of disease ranged from 13 to 22 years with an average of(19.00±3.06)years;body mass index(BMI)ranged from 21 to 28 kg·m-2 with an average of(23.53±2.47)kg·m-2;six patients(6 feet)with moderate hallux valgus defor-mity and 18 patients(30 feet)with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion com-bined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup.Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of(58.53±13.70)years old;the course of disease ranged from 8 to 25 years with an average of(17.94±3.92)years;BMI raged from 20 to 28 kg·m-2 with an average of(24.60±2.03)kg·m-2;4 patients(4 feet)with moderate bunion valgus deformity and 22 patients(36 feet)with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head.Operation time and postoperative complications between two groups were observed,hallux valgus angle(HVA),intermetatarsal angles between the first and the second metatarsals(I-MAFS),intermetatarsal angles between the first and fifth metatarsals(IMAFF),Japanese Society for Surgery of Foot(JSSF)score before surgery and at the latest follow-up were compared.Results Fifty patients were followed-up from 14 to 46(25.30± 8.83)months in resection group and 12 to 48 with an average of(24.30±1 1.12)months in preservation group,while no signifi-cant difference between two groups(P＞0.05).There were no significant difference in operation time and postoperative compli-cations between two groups(P＞0.05).JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from(45.09± 3.35)points,(38.90±13.67)°,(12.88±1.72)°,(32.50±2.99)° before operation to(81.60±3.27)points,(15.40±0.90),(9.06±2.27)°,(22.20±1.98)° at the latest follow-up(P＜0.05);preservation group were improved from(47.09±3.96)points,(43.30±12.65)°,(13.99±3.13)°,(33.20±6.14)° to(83.10±3.66)points,(15.20±1.54)°,(8.99±1.02)°,(24.70±1.88)°,respectively.There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before opera-tion and the latest follow-up(P＞0.05).At the latest follow-up,there were statistically significant differences in pain and defor-mity in JSSF scores between two groups(P＜0.05).Conclusion Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging re-sults.Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity.For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Objective To explore the effects of 1α,25-dihydroxyvitamin D3 on airway inflammation in asthmatic mice and the potential mechanisms.Methods Twenty-four female BALB/c mice in SPF grade were randomly divided into three groups(n=8):control group,asthma group,and asthma+VD3 group.On the 1st,8th,and 15th day,asthma group and asthma+VD3 group were given 0.2 ml ovalbumin(OVA)suspension for sensitization,while control group received 0.2 ml normal saline.On the 22-28th day,asthma group and asthma+VD3 group were challenged with 1%OVA atomization inhalation,while control group received an equal amount of normal saline atomization,for 30 minutes each time,once a day,for a continuous 7 days.Asthma+VD3 group was given intraperitoneal injection of 1α,25-dihydroxyvitamin D3 injection(4 μg/kg)30 minutes before each atomization,while control group and asthma group were given an equal dose of normal saline.After the last challenge,all mice were anesthetized,and serum,bronchoalveolar lavage fluid(BALF)and lung tissue samples were collected.HE staining and Periodic Acid Schiff(PAS)staining were used to observe the pathological changes in lung tissue and changes in airway mucus levels.ELISA was employed to detect serum IgE and inflammatory cytokines IL-4,IL-5 and IL-13 in BALF.Immunohistochemical technique and Western blotting were used to detect the expressions of SIRT1 and GATA-3 in mouse lung tissue.Results Compared with control group,asthma group had a significant increase in inflammatory cell infiltration around lung tissue,bronchia and accompanying perivascular,mainly characterized by eosinophils.Bronchial lumen stenosis,airway mucosal epithelial hyperplasia,and increased tracheal mucus secretion were also observed.The above changes in asthma+VD3 group were reduced compared with asthma group.Compared with control group,serum levels of IgE,and IL-4,IL-5,IL-13 inflammatory factors in BALF and GATA-3 in lung tissue were increased in asthma group(P<0.05),and SIRT1 level in lung tissue was significant decreased(P<0.05).Compared with asthma group,IgE level in serum,inflammatory factors of IL-4,IL-5 and IL-13 in BALF,and GATA-3 in lung tissue in asthma+VD3 group were decreased(P<0.05),and SIRT1 level in lung tissue was increased(P<0.05).Correlation analysis showed that the expression level of lung tissue SIRT1 was negatively correlated with the expression of GATA-3,serum IgG,and the levels of IL-4,IL-5,and IL-13 in BALF(P<0.05);the expression level of lung tissue GATA-3 was positively correlated with serum IgG and the levels of IL-4,IL-5,and IL-13 in BALF(P<0.05).Conclusion 1α,25-dihydroxyvitamin D3 can alleviate airway inflammation in asthmatic mice,possibly by upregulating the expression of SIRT1 in lung tissue and inhibiting the expression of GATA-3,thereby inhibiting inflammatory factors(IL-4,IL-5,IL-13).

NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.