BACKGROUND:Acute myocardial infarction can cause cardiac remodeling and heart failure,as well as skeletal myopathy,affecting patients'quality of life.Exercise therapy is an important rehabilitation method for patients with heart failure;however,the optimal exercise prescription has not been clarified. OBJECTIVE:To compare the effects of different exercise modes(aerobic exercise,resistance exercise)on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism,so as to provide a basis for optimizing the exercise rehabilitation program. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,myocardial infarction group,aerobic exercise group and resistance exercise group.Coronary artery ligation was used to create model of heart failure.After 3 months,animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions,while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages.After the experiment,maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively,and heart structure and function were evaluated by echocardiography.The heart was isolated,and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling.For the gstrocnemius muscle,ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area,dihydroethidium method was used to evaluate reactive oxygen species levels,enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity,western blot was used to determine the expression of ubiquitin-proteasome system proteins,and the number of activated satellite cells(Pax7+/MyoD+)were detected by double immunofluorescence staining. RESULTS AND CONCLUSION:(1)Exercise performance:Compared with the sham operation group,maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased(P<0.05);compared with the myocardial infarction group,the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased(P<0.05).(2)Cardiac remodeling:Compared with the sham operation group,infarction area,myocardial cell cross-sectional area,and collagen content in the myocardial infarction group increased(P<0.05),while leftventricular ejection fraction and shortening fraction decreased(P<0.05);compared with the myocardial infarction group,there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups(P>0.05).(3)Skeletal muscle remodeling:Compared with the sham operation group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,superoxide dismutase activity,glutathione peroxidase activity,and the number of activated satellite cells decreased in myocardial infarction group(P<0.05),while reactive oxygen species content,malondialdehyde content,and the protein expression of ubiquitin,MuRF1 and MAFbx increased(P<0.05);compared with the myocardial infarction group,gastrocnemius muscle mass index,superoxide dismutase activity,the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups(P<0.05),while reactive oxygen species content and the protein expression of ubiquitin,MuRF1,and MAFbx decreased(P<0.05);compared with the aerobic exercise group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,reactive oxygen species content,malondialdehyde content,the number of activated satellite cells increased in resistance exercise group(P<0.05),while superoxide dismutase activity,glutathione peroxidase activity down-regulated(P<0.05).To conclude,aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure,and the mechanism is related to reducing oxidative stress,inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling.Aerobic exercise has a better effect on improving skeletal muscle oxidative stress,while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.

BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

The 68 Center for Drug Evaluation recommend approved innovative drugs between 2019 and 2021 evaluation situation was summarized in this article,to analyzes the innovative drugs research and development trend and the influence of the drug evaluation and approval system reform.Meanwhile,after sorting out the clinical trials inspection report,to analyze the clinical trials on-site inspection of innovative drugs,and summarized the common defects,hope to provide reference and suggestions for subsequent innovative drug application and high-quality drug clinical trials.

Objective We aimed to evaluate the clinical efficacy of promoting blood circulation and eliminating phlegm method in preventing and treating patients with hydrocephalus after acute intracerebral hemorrhage.Methods This study included 139 patients with acute intracerebral hemorrhage who visited Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Guangyuan Hospital of Traditional Chinese Medicine,Affiliated Hospital of North Sichuan Medical College,Meishan Hospital of Traditional Chinese Medicine,and Xuyong Hospital of Traditional Chinese Medicine from September 2019 to June 2023.Patients who met the exposure factors of"using the method of promoting blood circulation and eliminating phlegm"were classified into the integrated Chinese and Western medicine cohort,while those who did not meet the exposure factors were classified into the Western medicine cohort.Clinical efficacy,incidence of hydrocephalus after intracerebral hemorrhage,sum of maximum distance between the anterior horn of the lateral ventricle and the head of the caudate nucleus(Huckman value),size of the hematoma,incidence of endpoint events,National Institutes of Health Stroke Scale(NIHSS)score,Modified Rankin Scale(mRS)score,and Barthel index score between two cohorts were compared.Results Total clinical effective rates for patients with hydrocephalus in the two cohorts were 60.0%and 75.0%,respectively.The total effective rate of the integrated Chinese and Western medicine cohort was higher than that of the Western medicine cohort(P<0.05).After 28 days of treatment,the incidence of hydrocephalus in patients in the integrated Chinese and Western medicine cohort was lower than that of the Western medicine cohort,and the Huckman value decreased compared with the Western medicine cohort(P<0.05).Compared with 24 hours after onset,both cohorts showed a reduction in hematoma size after 28 days of treatment;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort had reduced hematoma size(P<0.05).After 6 months of onset,the number of deaths in the integrated Chinese and Western medicine cohort decreased compared with the Western medicine cohort(P<0.05).Compared with 28 days of treatment,the NIHSS and mRS scores of the patients in both cohorts decreased after 6 months,while the Barthel index score increased;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort showed a decrease in the NIHSS and mRS scores after both 28 days of treatment and 6 months,while the Barthel index score increased(P<0.05).Conclusion Promoting blood circulation and eliminating phlegm can effectively prevent and treat hydrocephalus after intracerebral hemorrhage and does not increase the risk of bleeding within 24 hours.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Objective:This study was designed to explore the distribution pattern of TCM syndrome types in patients with Chronic Kidney Disease (CKD) stage 3-5 without alternative treatment after objective collection of TCM quad-diagnostic instruments.Methods:The four-diagnostic instruments of Chinese medicine were used to collect the four-diagnostic information of patients with stage CKD 3-5 non-alternative treatment for syndrome determination, and the correlation between TCM syndrome and basic disease characteristics of patients was analyzed.Results:The distribution of TCM syndrome types in 464 patients with CKD 3-5 stage non-substitution therapy was based on deficiency syndrome, and had both standard and solid syndrome. Qi-deficiency syndrome was the most common type, accounting for 24.6% (114/464), followed by kidney-yang deficiency syndrome, heart-qi deficiency syndrome, kidney-yin deficiency syndrome, heart-blood deficiency syndrome, spleen-yang deficiency syndrome and lung-yin deficiency syndrome. The positivism type of this deficiency is blood stasis, dampness-heat, moisture, turbidity and turbidity toxicity. There was no significant difference in gender and age distribution among patients with different CKD stages ( P>0.05), but the proportion of deficiency syndrome gradually increased with the increase of age. There were differences in the distribution of primary deficiency syndrome in different CKD stages ( χ2=57.48, P<0.001), but no difference in the distribution of primary deficiency syndrome ( χ2=2.59, P=0.957). Conclusions:According to the four diagnostic instrument of traditional Chinese medicine, the distribution of TCM syndrome types in patients with stage CKD3-5 non-alternative treatment is based on deficiency syndrome, combined with deficiency of primary and solid syndrome. The syndrome types in CKD3 stage were mainly qi deficiency and kidney qi deficiency, while the TCM syndrome types in CKD stage 4 were qi deficiency and kidney Yang deficiency. With the progression of the disease, the TCM syndromes of stage 5 CKD were mainly heart-qi deficiency and kidney-yang deficiency.

Objective:To investigate the safety and efficacy of pseudomonas aeruginosa Injection (PAI) in the treatment of coeliac leakage after cervical lymph node dissection for robotic thyroid cancer.Methods:Retrospective analysis of 1262 patients who underwent robotic thyroid surgery at the 960th Hospital of the People’s Liberation Army from Jan. 2021 to Aug. 2023 was made. Postoperative celiac leakage happened in 28 patients. The control and injection groups were divided according to whether pseudomonas aeruginosa injection was used or not. In the control group, there were 4 males and 11 females out of 15 patients, with an average age of (46.20±9.02) years old, and the treatment methods of low-fat diet, negative pressure suction, and pressure bandage were used. In the injection group, there were 7 males and 6 females among 13 patients, with an average age of (41.00±8.87) years. They were treated with low-fat diet, negative pressure suction, pressure bandage, and PAI .The number of lymph node dissection, total drainage volume, peak drainage volume, days of hospitalization and the rate of decline in drainage volume within 24 h after the use of PAI in the injection group, post-injection temperature, number of injections, and post-injection extubation time were statistically analyzed in both groups. Independent samples t test, Mann-Whitney U test, χ2 test or Fisher’s exact test were used for comparison between groups. Results:There was no statistically significant difference in age, gender, extent of thyroidectomy, highest daily drainage volume, and total drainage volume between the two groups ( P>0.05). The difference in the number of lymph node dissection (49.15±23.05 vs. 30.80±11.76, P=0.012) and hospitalization time (11.77±4.64 vs. 16.40±6.42, P=0.041) between the injection group and the control group was statistically significant. After the use of pseudomonas aeruginosa injection, the draining fluid decreased from the previous day (69.56± 20.82) % in the injection group; Twelve patients were successfully extubated after one injection of pseudomonas aeruginosa injection, and one patient was successfully extubated after two injections; the mean time to extubation after injection was (3.85±1.28) days; 76.9% patients (10/13) had fever symptoms within 48 h with body temperature (38.05±0.89) ℃ after injection, body temperature returned to normal after symptomatic treatment,and no other adverse reactions occurred except fever. Conclusion:Pseudomonas aeruginosa injection is safe and effective in the treatment of celiac leakage after cervical lymph node dissection for robotic thyroid cancer, effectively reducing cervical drainage and shortening hospitalization days.