BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.

Objective:To discuss the effect of Jiegeng Yuanshen Tang(JGYST)on airway tissue inflammation and mucus secretion in the mice with allergic asthma,and to clarify the related mechanism.Methods:Forty male C57BL/J mice were randomly divided into control group,JGYST group,ovalbumin(OVA)group,and OVA + JGYST group.The mice in OVA group and OVA +JGYST group were sensitized with 50 μg OVA via intraperitoneal injection twice weekly,followed by 20 μg OVA nasal drops daily for 7 d to induce asthma;the mice in OVA +JGYST group were gavaged with 200 μL JGYST 1 h before each OVA challenge,and the administration lasted for 7 d;the mice in control group were given equivalent dose of PBS via intraperitoneal injection,nasal drops,and gavage;the mice in JGYST group were given the same dose of PBS for intraperitoneal and nasal administration and gavaged with the same dose of JGYST.The pathomorphology of lung tissue of the mice in various groups was observed by HE staining and periodic acid-Schiff(PAS)staining,and the inflammation and PAS scores were calculated;flow cytometry method was used to detect the numbers of eosinophils,neutrophils,helper T lymphocyte 1(Th1)cells,helper T lymphocyte 2(Th2)cells,and dendritic cells(DCs),as well as the percentage of mature DCs and level of reactive oxygen species(ROS)in lung tissue of the mice in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukin-4(IL-4),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)mRNA in lung tissue of the mice in various groups.Results:The HE and PAS staining results showed that the mice in control group had intact airway and alveolar structure,without infiltration of inflammatory cells or mucus secretion;compared with control group,there was a large number of infiltrating inflammatory cells in airway tissue of the mice in OVA group,and the inflammation and PAS scores were increased(P<0.01);compared with OVA group,the infiltration of inflammatory cells in airway tissue of the mice in JGYST group and OVA + JGYST group was decreased,and the inflammation and PAS scores were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the numbers of eosinophils,Th2 cells,and DCs in lung tissue of the mice in OVA group were increased(P<0.05 or P<0.01),and the percentage of mature DCs and level of ROS were significantly increased(P<0.01);compared with OVA group,the numbers of eosinophils,Th2 cells,and DCs in lung tissue of the mice in JGYST group and OVA + JGYST group were decreased(P<0.01),and the percentage of mature DCs and level of ROS were significantly decreased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of IL-4,IL-10,and TNF-α mRNA in lung tissue of the mice in OVA group were increased(P<0.01);compared with OVA group,the expression levels of IL-4 and TNF-α mRNA in lung tissue of the mice in JGYST group and OVA + JGYST group were decreased(P<0.01),while the expression level of IL-10 mRNA was increased(P<0.01).Conclusion:JGYST can alleviate the airway tissue inflammation and mucus secretion in the mice with allergic asthma,and its mechanism may be related to reducing the number of Th2 cells and DCs,decreasing the ROS level and expression level of proinflammatory cytokine,and increasing the expression level of anti-inflammatory cytokine.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Objective:To analyze identification of copper death gene related subtypes,construction of prognosis model and influence of immune infiltration in osteosarcoma(OS)on basis of copper death gene.Methods:Survival and prognosis of OS associated copper death gene were analyzed combining by TARGET and GEO database.OS was divided into different subtypes of copper death by consistent clustering method.SSGSEA was used to analyze difference of immune cells in classification of copper death.Setting P value= 0.05 and q value=0.05,GO and KEGG enrichment analysis were performed on differential genes of copper death typing.Prognosis model was constructed according to results of Lasso regression analysis and cross validation,risk assessment analysis and ROC curve were used to evaluate accuracy of model prediction.Combined with clinical characteristics,nomograms were constructed to predict survival time of patients,and risk differences were analyzed.Immune cell infiltration and tumor microenvironment analysis were performed on OS samples."pRRophetic"package in R software was used to analyze drug sensitivity of OS samples.Results:FDX1,GLS,DLAT and PDHB as high-risk genes for OS prognosis were identified.According to copper death classification of OS samples,OS could be divided into two types:CRGclusterA and CRGclusterB.CRGclusterA was associated with Th2 cells,and CRGclusterB was associated with Th1 cells.Most OS copper death genes were highly expressed in CRGclusterA.Immune cell infiltration analysis results showed that γδ T cells,resting mast cells and resting dendritic cells were positively correlated with risk score,while CD8 T cells were negatively correlated with risk score.Drug sensitivity analysis showed that OS showed higher sensitivity to Elesclomol and GW.441756.Conclusion:Two subtypes of CRGclusterA and CRGclusterB are identified in this study.Four high-risk prognostic genes FDX1,GLS,DLAT and PDHB are identified,providing new insights into prognostic evaluation and immunotherapy target candidates for OS.

Objective To prepare asenapine maleate microemulsion gel(ASPM-Emulgel)and evaluate its brain targeting by nasal administration.Methods The prescription composition and dosage of asenapine maleate microemulsion(ASPM-Emul)was determined according to the equilibrium solubility of asenapine maleate(ASPM)in different oils,emulsifiers,co-emulsifiers and the compatibility results of excipients,and ASPM-Emul was prepared into a gel with carbomer 940 as the gel matrix.The particle size distribution and microstructure of ASPM-Emul were investigated.The in vitro release rates and permeability in sheep nasal mucosa of ASPM-Emul and ASPM Emulgel were compared using the Franz diffusion cell method.The nasal ciliary toxicity of ASPM-Emulgel was investigated using the in vivo toad maxillary model method.Brain targeting of ASPM-Emulgel by nasal administration in rats was evaluated.Results According to the results of equilibrium solubility and compatibility,Maisine 35-1,Tween 80 and Transcutol P were selected as the oil phase,emulsifier and co-emulsifier of ASPM-Emul,respectively,with the ratio of 4 ∶ 4 ∶ 2.ASPM-Emul was a light blue semi-transparent microemulsion with a particle size of(73.6±7.4)nm.The microemulsion was regularly spherical and uniformly dispersed under transmission electron microscopy.The results of in vitro release and permeation showed that the release rate of ASPM-Emul was relatively fast,while the release rate of ASPM-Emulgel remained stable.However,the permeability of the two formulations in sheep nasal mucosa was basically similar.ASPM-Emul and ASPM-Emulgel showed no significant toxicity to nasal cilia of toad.Compared with the tail vein ASPM group,the drug content in the brain of ASPM-Emul and ASPM-Emulgel significantly increased after nasal administration,both exhibiting significant brain targeting,and the drug targeting efficiency(DTE)of ASPM-Emulgel was higher.Conclusion The preparation of ASPM into microemulsion gel can significantly improve the brain targeting after nasal administration,and is expected to improve the clinical therapeutic effect of ASPM.

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory′s experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P＞0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P＜0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P＜0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P＜0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P＜0.01),the expression level of γH2AX(P＜0.05),and the ROS level(P＜0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P＜0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P＜0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P＜0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P＜0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P＜0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P＜0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P＜0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.