OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective To explore the potential causal relationship between occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") and five mental disorders (depression, bipolar disorder, schizophrenia, insomnia and anxiety) using the two-sample Mendelian randomization (MR) method. Methods Single nucleotide polymorphisms (SNPs) loci associated with pneumoconiosis and five mental disorders were screened from Genome-Wide Association Studies. Inverse variance weighting (IVW), weighted median (WM) and MR-Egger regression methods were used to evaluate the significance of the causal relationship between pneumoconiosis and five mental disorders. Sensitivity analysis was used to evaluate the accuracy and reliability of the research results. Results After matching data of pneumoconiosis and the five mental disorders, 16 SNPs were ultimately included as instrumental variables in this study. The result of MR analysis revealed a positive causal relationship between pneumoconiosis and both depression [IVW: odds ratio (OR) and 95% confidence interval (CI) was 1.017 (1.000-1.035), P<0.05] and bipolar disorder [IVW: OR(95%CI)was 1.046(1.009-1.083), P<0.05; WM: OR (95%CI) was 1.055(1.007-1.105), P<0.05]. Result of sensitivity analysis indicated there was no heterogeneity and horizontal pleiotropy in the above results. There was no causal association observed between pneumoconiosis and schizophrenia, insomnia, or anxiety disorders (all P>0.05). Conclusion This study provides genetic evidence supporting a positive causal relationship between pneumoconiosis and both depression and bipolar disorder.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Objective:To observe the differences in clinical efficacy of Jieyu Anshen Decoction combined with auricular points and oral tibolone in the treatment of patients with perimenopausal sleep disorders, and provide effective treatment for patients with contraindications to hormone supplement therapy in clinicalMethods:Using a randomized trial design, from July 2018 to August 2020,102 perimenopausal insomnia patients in International Peace Maternity and Child Health Hospital of China Welfare Institutewith kidney deficiency and liver depression who met the inclusion criteria were randomly divided into a treatment group and a control group with 51 cases each. The treatment group took Jieyu Anshen Recipe. At the same time, unilateral auricular point pressing treatment was given, and the opposite ear was changed in 5 d. The control group was treated with tiburon for a period of 3 months. The changes in the scores of each scale were observed in the two groups after 1 month and 3 months treatment. The scale included Pittsburgh sleep quality index (PSQI), modified Kupperman score (KMI), Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire Depression Screening Scale (PHQ-9). Its effectiveness and differences were evaluated and analyzed comprehensively through the above scale.Results:PSQI, KMI, GAD-7, PHQ-9 scores decreased significantly in the control and treatment groups after 1 month and 3 months of treatment, and the difference were statistically significant: PSQI: (8.58 ± 1.94) and (5.81 ± 1.93) scores vs. (13.10 ± 2.53), (9.15 ± 2.59) and (6.33 ± 1.98) scores vs.(13.52 ± 2.27) scores; KMI: (19.92 ± 2.16) and (14.67 ± 4.11) scores vs. (28.54 ± 7.65) scores, (19.02 ± 5.92) and(14.10 ± 4.37) scores vs. (27.42 ± 7.34) scores; GAD-7: (4.54 ± 2.03) and (3.81 ± 1.63) scores vs. (5.69 ± 2.95) scores, (3.71 ± 2.48) and (3.32 ± 1.73) scores vs. (4.90 ± 3.17) scores; PHQ-9:(6.90 ± 2.52) and (4.98 ± 1.96) scores vs. (9.83 ± 3.71) scores, (6.15 ± 2.62) and (4.44 ± 1.81) scores vs. (9.02 ± 3.73) scores ( P<0.01). PSQI, KMI, PHQ-9, and GAD-7 scores declined between the two groups, but there were no significant differences between the two groups ( P>0.05). After 1 month and 3 months of treatment, using PSQI scale and KMI score, the total efficiency of patients in the control group was slightly higher than that of the treatment group, but the difference was not statistically significant ( P>0.05); after 1 month and 3 months of treatment, using PHQ-9 score and GAD-7 score, the total efficiency of patients in the treatment group was slightly higher than that of the control group, but the difference was not statistically significant ( P>0.05). Conclusions:Traditional Chinese medicine combined with ear acupoint pressing has similar effects to tibolone in treating perimenopausal insomnia with kidney deficiency and liver depression. It can significantly improve the quality of sleep and quality of life of patients, and has good safety. For patients who are not suitable for hormone, Chinese medicine can be used as an alternative. The therapies are worthy of clinical application.

This study explores the construction and application of online platform for medical continuing education based on libraries and academic conferences. With the consent of the experts participating in the conference, the contents of the conferences are recorded and made into learning videos for continuing education. By constructing network servers, cloud services, and other platforms, the online continuing education can be realized, and such procedures as giving credits also can be completed. And combined with other professional continuing education platforms, a complete continuing education system can be constructed. We have initially designed out the construction mode of medical continuing education platform. The construction of medical continuing education platform has enhanced the class or position of the symposium organization institutions, facilitated the continuing education of professionals and technical personnel, with good social and economic effects, which is worthy of promotion.

The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials. To solve this problem, we constructed a ternary platinum nanoparticle, reduced graphene oxide, multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method. Under the optimized conditions, the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin. The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05-50μM with a detection limit of 0.01μM (S/N = 3). The linear range for rutin was 0.05-50μM with a detection limit of 0.005μM (S/N = 3). The ternary nanocomposite sensor also exhibited good reproducibility and stability, and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57％and 108.46％.

An ultrasensitive electrochemical sensor based on polydopamine/carboxylic multi-walled carbon nano-tubes (MWCNTs-COOH) nanocomposites modified glassy carbon electrode (GCE) was presented in this work, which has been developed for highly selective and highly sensitive determination of an anti-microbial drug, metronidazole. The preparation of polydopamine/MWCNTs―COOH nanocomposites/GCE sensor is simple and possesses high reproducible, where polydopamine can be coated on the surface of MWCNTs―COOH via a simple electropolymerization process. Under optimized conditions, the proposed sensor showed ultrasensitive determination for metronidazole with a wide linear detection range from 5 to 5000μmol/dm3 and a low detection limit of 0.25μmol/dm3 (S/N = 3). Moreover, the proposed sensor has been successfully applied for the quantitative determination of metronidazole in real drug samples. This work may provide a novel and effective analytical platform for determination of me-tronidazole in application of real pharmaceutical and biological samples analysis.