BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

BACKGROUND:Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis,but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE:To determine whether there is a causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fractures in Asian and European populations,respectively,using a comprehensive two-sample Mendelian randomized analysis. METHODS:Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank,a British biological bank. Data of hypertension,multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method,MR-Egger regression method,weighted median method,weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness,heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION:In Asian populations,there was no significant genetic predictive causal relationship between hypertension and osteoporosis,and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations,hypertension had a negative causal relationship with osteoporosis,and there was no significant causal relationship between hypertension and systemic bone mineral density,calcaneal bone mineral density,forearm bone mineral density and osteoporosis with fracture. According to the stsiger test,there was no reverse causal relationship between osteoporosis,multiplesite bone mineral density,osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis,that is,in Asian populations,hypertension and calcaneal bone mineral density show a positive causal relationship;in European populations,hypertension and osteoporosis show a negative causal relationship,but no reverse causal relationship.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

BACKGROUND:Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis,but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE:To determine whether there is a causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fractures in Asian and European populations,respectively,using a comprehensive two-sample Mendelian randomized analysis. METHODS:Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank,a British biological bank. Data of hypertension,multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method,MR-Egger regression method,weighted median method,weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness,heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION:In Asian populations,there was no significant genetic predictive causal relationship between hypertension and osteoporosis,and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations,hypertension had a negative causal relationship with osteoporosis,and there was no significant causal relationship between hypertension and systemic bone mineral density,calcaneal bone mineral density,forearm bone mineral density and osteoporosis with fracture. According to the stsiger test,there was no reverse causal relationship between osteoporosis,multiplesite bone mineral density,osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis,that is,in Asian populations,hypertension and calcaneal bone mineral density show a positive causal relationship;in European populations,hypertension and osteoporosis show a negative causal relationship,but no reverse causal relationship.

Endovascular mechanical thrombectomy is an important progress in the treatment of acute ischemic stroke,and early and timely endovascular mechanical thrombectomy can provide significant clinical benefits.The treatment mode of endovascular therapy after intravenous thrombolysis is bridging therapy,while the traditional bridging therapy may have limitations such as time delay and increased bleeding risk.In recent years,with the completion of several large scale randomized controlled trial,whether to bypass intravenous thrombolysis and directly perform mechanical thrombectomy has become a hot topic in the field of stroke treatment.In addition,the third generation of thrombolytic drug Tenecteplase has a more convenient way of administration,it also provides new ideas for bridging therapy.This article compares and analyzes the benefits and risks of direct mechanical thrombectomy therapy and bridging therapy based on relevant research that has been completed,aiming to provide reference for the correct selection of treatment methods for acute ischemic stroke patients.

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.

The infectious disease outpatient service as a frontier is an important fulcrum of public health service. Its standardized construction is an important support for ensuring medical safety, reducing nosocomial infections, and controlling the epidemic of infectious diseases. The sub-specialty outpatient service of infection diseases includes fever outpatient service, intestinal outpatient service, tuberculosis outpatient service, AIDS outpatient service, liver disease outpatient service, etc. According to the characteristics of each subspecialty outpatient service and combining with clinical practice, we elaborated the setting norms of subspecialty outpatient service for common infectious diseases from the perspective of planning and design, building layout, equipment and facilities configuration, staffing, daily management and demonstration.

Cellular signaling networks act as the central processor to deal with environmental signals and regulate cell function, and determine cell fate. Using synthetic biology approach to engineer cell signaling networks is crucial for ultimately constructing man-made "cell machines". Cellular signaling networks can encode sophisticated cell information by processing quantitatively signaling dynamics, which enables multi-dimensional regulation of functional sub-circuits. Here, we first review the research progresses on the signaling coding mechanisms; and then elaborate the methodologies and applications of cells signaling engineering; finally, we envision that signaling-based cell engineering are important for the increasingly-complicated next generation synthetic biology.

BACKGROUND:Nerve growth factor has been shown to play an important role in bone healing, but little is reported on the effect of growth factor composite scaffolds via the immediate implantation in the repair of canine bone defects. OBJECTIVE:To analyze the effect of nerve growth factor composite scaffolds via the immediate implantation for the repair of canine bone defects. METHODS:Nerve growth factor composited strontium apatite scaffolds were prepared. Canine mandibular defect models were established and divided into three groups, fol owed by implanted with composite scaffold (experimental group), strontium apatite (positive control group), or nothing (blank control group). The three-dimensional CT reconstruction and hematoxylin-eosin staining of canine mandibular bone defects were observed. RESULTS AND CONCLUSION:In the blank control group, there were few new bones surrounding bone defect. Trabecular bones spread from the defect center to the surrounding tissues in the experimental and positive control groups. The bone density, volume, thickness, and implant-bone contact were significantly increased, while the trabecular separation was significantly decreased in the experimental group compared with the positive control and blank control groups (P<0.05), and al above indicators in the positive contro group were significantly higher than those in the blank control group (P<0.05). Hematoxylin-eosin staining showed that in the experimental group, there were a large number of new bones that contacted with the surrounding bones closely, and trabecular bones arranged regularly. In the positive control group, newborn osteoid, trabeculare, and a smal amount of debris were found. In the blank control group, few new bones were connected with the surrounding bones untightly and trabecular bone arranged irregularly. These results indicate that the nerve growth factor composite scaffold can promote the bone regeneration in the canine bone defects after immediate implantation.

Objective To research the tourniquet effect on cement mantle thickness in total knee arthroplasty.Methods From June 2013 to June 2014,112 cases of patients were received total knee arthroplasty in the First People's Hospital of Foshan and 94 cases of which received primary operation,82 cases were recruited of the research and randomly divided into experimental group(n=41) without tourniquet and control group(n =41)with tourniquet.The radiological cement mantle thickness was evaluated postoperatively in 2 zones (tibia) on anteroposterior and 4 zones (tibia 2;femur 2) on lateral radiographs,and values were cumulated.Additionally,the calculated blood loss,haemoglobin loss,blood transfusion rate,average transfusion volume,VAS pain score,arc of motion,swelling,ecchymosis and micro thrombus in venules were recorded.Results The study showed that (3.57± 0.62) mm on without tourniquet group and(3.74 ±0.71)mm on tourniquet group in tibia (P=0.240).However,the cement mantle thickness of mm on without tourniquet group(2.00±0.43) mm on tourniquet group(2.19±0.48) in femur (P=0.053),there was no statistically significant difference between two groups.The tourniquet group were reduced on the calculated blood loss,haemoglobin loss,blood transfusion rate and average transfusion volume compared with without tourniquet group(P＜0.05).But VAS pain score,arc of motion,swelling,ecchymosis and micro thrombus in venules were slightly increased in tourniquet group compared with without tourniquet group (P＜0.05).Conclusion The use of a tourniquet in total knee arthroplasty can reduce the calculated blood loss,haemoglobin loss,blood transfusion rate,average transfusion volume,but without using a tourniquet has a better clinical results.