BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Objective:To analyse the characteristics and development of oral mucosal diseases trials registered in the Chinese Clini-cal Trial Registry(ChiCTR).Methods:The ChiCTR database was searched to collect all studies related to oral mucosal diseases from July 25,2007 to September 30,2022.Statistical analysis was conducted on the names of oral mucosal diseases,registration dates,ge-ographical distribution,registration status,ethics committee approval,funding source,sample size,study type and design and blind-ing method.Results:312 registered studies related to oral mucosal diseases were collected.The diseases were mainly herpes zoster,hand-foot-and-mouth disease,radiotherapy-induced oral mucositis,pemphigus and oral lichen planus.The number of registered pro-jects basically showed an increasing trend.The institutions involved in the implementation of the study were mainly located in Beijing,Sichuan,Shanghai,Guangdong and Jiangsu,accounting for 55.02％of the total(340/618).The top 5 provinces and cities in terms of number of registered projects were Beijing,Sichuan,Jiangsu,Shanghai and Guangdong,accounting for 62.5％of the total included trials(195/312).Single-centre studies accounted for 77.56％(242/312),259 studies(83.01％)were pre-registered and 53(16.99％)were supplementary registrations,262(83.97％)studies were approved by the ethics committee.284 studies(91.03％)had their funding status marked,and a total of 301 grants were received,of which the top 3 were 31.89％(96/301)and were self-funded,23.26％(70/301)were funded by hospitals and 19.93％(60/301)were funded by local governments.The types of studies were mainly interventional studies 67.31％(210/312),followed by observational studies 17.31％(54/312).The research designs were mainly randomized parallel controlled trials,accounting for 63.14％(197/312),of which only 52(26.4％)studies explicitly stated the use of blinding,and 137(69.54％)studies were unspecified or blank in the blinding section.Conclusion:The studies on oral mucosal diseases registered in ChiCTR shows a trend of increasing year by year,the regional distribution is uneven,the number of multi-centre clinical trials is relatively small,and there is still room for improvement in study design and the application of blind ness method.

Objective:To investigate the factors influencing the efficacy of etanercept in the treatment of toxic epidermal necrolysis (TEN) across different countries and regions.Methods:A total of 17 articles (case analyses or case reports) were selected through a comprehensive search in 4 Chinese databases (CNKI, Wanfang, VIP, and SinoMed) and 4 English databases (PubMed, Cochrane Library, Embase, and Elsevier SD). Clinical data from 52 patients originating from 7 countries were collected. Independent variables included age, sex, race, culprit drugs, disease severity, presence or absence of complications, initial dose, timing of administration, number of administrations of etanercept, and combination therapy; and the duration of hospitalization served as the dependent variable. Univariate and multiple linear regression analyses were conducted sequentially.Results:Among the 52 patients, 26 were male and 26 were female, with a median age M ( Q1, Q3) of 57.0 (36.0, 71.5) years. The median hospitalization duration was 12.0 (8.0, 17.5) d, and the median severity-of-illness score for TEN (SCORTEN) was 2 (2, 4). A total of 33 patients (63.5%) had at least one comorbidity. The initial etanercept dose was 50 mg in 37 patients (71.2%). The median timing of etanercept administration was 3 (3, 6) days after disease onset. Etanercept was used as monotherapy in 26 patients (50.0%) and as combination therapy in 26 patients (50.0%). Multiple linear regression analysis showed that age (partial regression coefficient β [95% CI]: -0.106 [-0.194, -0.018]), disease severity (2.216 [0.452, 3.980]), timing of administration (1.343 [0.827, 1.858]), and combination therapy (11.993 [4.149, 19.838]) significantly influenced the hospitalization duration of TEN patients (all P < 0.05). However, sex, race, presence of comorbidities, initial dose, and number of administrations did not affect hospitalization duration (all P > 0.05). Based on the standardized regression coefficients, the factors influencing hospitalization duration in TEN patients were ranked from strongest to weakest as follows: timing of administration (0.632), combination therapy (0.595), disease severity (0.337), and age (-0.233) . Conclusions:Early administration of etanercept is the key to achieving clinical benefit in the treatment of TEN. In cases where the response is inadequate or the condition is severe, combination therapy may be considered.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective:To investigate the factors influencing the efficacy of etanercept in the treatment of toxic epidermal necrolysis (TEN) across different countries and regions.Methods:A total of 17 articles (case analyses or case reports) were selected through a comprehensive search in 4 Chinese databases (CNKI, Wanfang, VIP, and SinoMed) and 4 English databases (PubMed, Cochrane Library, Embase, and Elsevier SD). Clinical data from 52 patients originating from 7 countries were collected. Independent variables included age, sex, race, culprit drugs, disease severity, presence or absence of complications, initial dose, timing of administration, number of administrations of etanercept, and combination therapy; and the duration of hospitalization served as the dependent variable. Univariate and multiple linear regression analyses were conducted sequentially.Results:Among the 52 patients, 26 were male and 26 were female, with a median age M ( Q1, Q3) of 57.0 (36.0, 71.5) years. The median hospitalization duration was 12.0 (8.0, 17.5) d, and the median severity-of-illness score for TEN (SCORTEN) was 2 (2, 4). A total of 33 patients (63.5%) had at least one comorbidity. The initial etanercept dose was 50 mg in 37 patients (71.2%). The median timing of etanercept administration was 3 (3, 6) days after disease onset. Etanercept was used as monotherapy in 26 patients (50.0%) and as combination therapy in 26 patients (50.0%). Multiple linear regression analysis showed that age (partial regression coefficient β [95% CI]: -0.106 [-0.194, -0.018]), disease severity (2.216 [0.452, 3.980]), timing of administration (1.343 [0.827, 1.858]), and combination therapy (11.993 [4.149, 19.838]) significantly influenced the hospitalization duration of TEN patients (all P < 0.05). However, sex, race, presence of comorbidities, initial dose, and number of administrations did not affect hospitalization duration (all P > 0.05). Based on the standardized regression coefficients, the factors influencing hospitalization duration in TEN patients were ranked from strongest to weakest as follows: timing of administration (0.632), combination therapy (0.595), disease severity (0.337), and age (-0.233) . Conclusions:Early administration of etanercept is the key to achieving clinical benefit in the treatment of TEN. In cases where the response is inadequate or the condition is severe, combination therapy may be considered.

Objective:To investigate the effect of Euphorbia Lathyrol on expressions of IL-7,IL-10 and VEGF in renal clear cell neoplasias(RCCN)mice by regulating TGF-β/Smad signaling pathway.Methods:RCCN xenograft mice were established and divided into model group,Euphorbia Lathyrol group and Cisplatin group.Euphorbia Lathyrol group were given 20 mg/kg Euphorbia Lathyrol solution intragastric administration,model group were given 0.9%NaCl gastric feeding,Cisplatin group were given intraperito-neal injection of 4 mg/kg cisplatin solution,then mice weight and tumor volume were recorded.Expressions of TGF-β1,Smad2 and Smad4 were tracked down through Western blot.Expressions of immune factors IL-7 and IL-10 in serum of xenograft mice were detected by ELISA.Expression of VEGF in tumor mass was detected by IHC.Results:After 14 days of administration,compared with model group,the proliferation of tumor grafts in Cisplatin group and Euphorbia Lathyrol group was inhibited(P<0.05),and the expressions of TGF-β1,Smad2,Smad4 protein and VEGF were observably decreased(P<0.05),expressions of IL-7 in serum was increased,while level of IL-10 in serum was decreased(P<0.05).Conclusion:Euphorbia Lathyrol is able to reduce expressions of IL-7,IL-10,as well as VEGF in RCCN xenograft mice by impeding TGF-β1/Smad signaling transduction system.

Objective To explore the motor coordination characteristics of the attack leg of the athletes under scoring actions in the front roundhouse kick of competitive taekwondo,and provide a theoretical basis for coaches to formulate precise training strategies in stages and segments so as to enhance the efficiency and success rate of the athletes' movements.Methods Kinematic data and surface electromyography signals were collected from 15 elite Taekwondo athletes during different phases of the front roundhouse kick.The continuous relative phase(CRP)method was used to calculate the joint coordination and variability of continuous relative phase(VCRP),while non-negative matrix factorization and k-means clustering were used to analyze muscle synergy characteristics.Results The coupling of the neural launch phase was dominated by knee-ankle coupling in coronal axis and hip-ankle coupling in sagittal axis.The coupling of the kicking phase was dominated by hip-knee,hip-ankle in coronal axis,and knee-ankle coupling in vertical axis.The coupling of the recovery phase was dominated by hip-knee,hip-ankle coupling in coronal axis,and knee-ankle coupling in sagittal axis.These coupling relationships remained relatively stable around 0 rad.Approximately 80.0％VCRP remained stable across all phases,with minor fluctuations occurring at phase transitions.A total of 4,5,and 4 muscle synergy clusters were identified in neural launch,kicking,recovery phases,respectively.There were significant differences in the mean gap values among phases(P＜0.001).However,there were no significant differences in the mean sparsity values among phases(P＞0.05).Some muscle synergies were shared across phases,while others differentiated to form phase-specific coordination patterns.Conclusions Joint coordination in each phase exhibited 1-3 primary stable patterns with flexibility during transitions.Muscle coordination was dynamically adjusted throughout the motion,and a general muscle synergy pattern functioned consistently across different phases,whereas a differentiated muscle synergy pattern fulfilled the phase-specific functional demands.The neural launch and kicking phases should be focused on during training,with the emphasis on controling over critical points to optimize performance.

Objective:To investigate the effect of Euphorbia Lathyrol on expressions of IL-7,IL-10 and VEGF in renal clear cell neoplasias(RCCN)mice by regulating TGF-β/Smad signaling pathway.Methods:RCCN xenograft mice were established and divided into model group,Euphorbia Lathyrol group and Cisplatin group.Euphorbia Lathyrol group were given 20 mg/kg Euphorbia Lathyrol solution intragastric administration,model group were given 0.9%NaCl gastric feeding,Cisplatin group were given intraperito-neal injection of 4 mg/kg cisplatin solution,then mice weight and tumor volume were recorded.Expressions of TGF-β1,Smad2 and Smad4 were tracked down through Western blot.Expressions of immune factors IL-7 and IL-10 in serum of xenograft mice were detected by ELISA.Expression of VEGF in tumor mass was detected by IHC.Results:After 14 days of administration,compared with model group,the proliferation of tumor grafts in Cisplatin group and Euphorbia Lathyrol group was inhibited(P<0.05),and the expressions of TGF-β1,Smad2,Smad4 protein and VEGF were observably decreased(P<0.05),expressions of IL-7 in serum was increased,while level of IL-10 in serum was decreased(P<0.05).Conclusion:Euphorbia Lathyrol is able to reduce expressions of IL-7,IL-10,as well as VEGF in RCCN xenograft mice by impeding TGF-β1/Smad signaling transduction system.

Objective:To analyse the characteristics and development of oral mucosal diseases trials registered in the Chinese Clini-cal Trial Registry(ChiCTR).Methods:The ChiCTR database was searched to collect all studies related to oral mucosal diseases from July 25,2007 to September 30,2022.Statistical analysis was conducted on the names of oral mucosal diseases,registration dates,ge-ographical distribution,registration status,ethics committee approval,funding source,sample size,study type and design and blind-ing method.Results:312 registered studies related to oral mucosal diseases were collected.The diseases were mainly herpes zoster,hand-foot-and-mouth disease,radiotherapy-induced oral mucositis,pemphigus and oral lichen planus.The number of registered pro-jects basically showed an increasing trend.The institutions involved in the implementation of the study were mainly located in Beijing,Sichuan,Shanghai,Guangdong and Jiangsu,accounting for 55.02％of the total(340/618).The top 5 provinces and cities in terms of number of registered projects were Beijing,Sichuan,Jiangsu,Shanghai and Guangdong,accounting for 62.5％of the total included trials(195/312).Single-centre studies accounted for 77.56％(242/312),259 studies(83.01％)were pre-registered and 53(16.99％)were supplementary registrations,262(83.97％)studies were approved by the ethics committee.284 studies(91.03％)had their funding status marked,and a total of 301 grants were received,of which the top 3 were 31.89％(96/301)and were self-funded,23.26％(70/301)were funded by hospitals and 19.93％(60/301)were funded by local governments.The types of studies were mainly interventional studies 67.31％(210/312),followed by observational studies 17.31％(54/312).The research designs were mainly randomized parallel controlled trials,accounting for 63.14％(197/312),of which only 52(26.4％)studies explicitly stated the use of blinding,and 137(69.54％)studies were unspecified or blank in the blinding section.Conclusion:The studies on oral mucosal diseases registered in ChiCTR shows a trend of increasing year by year,the regional distribution is uneven,the number of multi-centre clinical trials is relatively small,and there is still room for improvement in study design and the application of blind ness method.

Objective To explore the motor coordination characteristics of the attack leg of the athletes under scoring actions in the front roundhouse kick of competitive taekwondo,and provide a theoretical basis for coaches to formulate precise training strategies in stages and segments so as to enhance the efficiency and success rate of the athletes' movements.Methods Kinematic data and surface electromyography signals were collected from 15 elite Taekwondo athletes during different phases of the front roundhouse kick.The continuous relative phase(CRP)method was used to calculate the joint coordination and variability of continuous relative phase(VCRP),while non-negative matrix factorization and k-means clustering were used to analyze muscle synergy characteristics.Results The coupling of the neural launch phase was dominated by knee-ankle coupling in coronal axis and hip-ankle coupling in sagittal axis.The coupling of the kicking phase was dominated by hip-knee,hip-ankle in coronal axis,and knee-ankle coupling in vertical axis.The coupling of the recovery phase was dominated by hip-knee,hip-ankle coupling in coronal axis,and knee-ankle coupling in sagittal axis.These coupling relationships remained relatively stable around 0 rad.Approximately 80.0％VCRP remained stable across all phases,with minor fluctuations occurring at phase transitions.A total of 4,5,and 4 muscle synergy clusters were identified in neural launch,kicking,recovery phases,respectively.There were significant differences in the mean gap values among phases(P＜0.001).However,there were no significant differences in the mean sparsity values among phases(P＞0.05).Some muscle synergies were shared across phases,while others differentiated to form phase-specific coordination patterns.Conclusions Joint coordination in each phase exhibited 1-3 primary stable patterns with flexibility during transitions.Muscle coordination was dynamically adjusted throughout the motion,and a general muscle synergy pattern functioned consistently across different phases,whereas a differentiated muscle synergy pattern fulfilled the phase-specific functional demands.The neural launch and kicking phases should be focused on during training,with the emphasis on controling over critical points to optimize performance.