BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To determine the impact of progressive rehabilitation intervention based on the FITT principle on the recovery of elderly patients with acute ST-segment elevation myocardi-al infarction(STEMI)after percutaneous coronary intervention(PCI).Methods A total of 184 STEMI patients admitted to our hospital between December 2021 and June 2023 were enrolled and randomly divided into a study group(n=92)and a control group(n=92).Routine rehabilita-tion intervention was given to the control group,and progressive rehabilitation intervention based on the FITT principle was given to the study group.Both groups were intervened for 12 weeks.Metabolite equivalents(MET)of the two groups were evaluated before and at 4,8 and 12 weeks after intervention.Their cardiopulmonary reserve function and quality of life were evaluated with cardiopulmonary exercise testing and myocardial infarction multidimensional assessment scale(MIDAS)before and at 12 weeks after intervention.The incidence of adverse cardiovascular events such as ventricular arrhythmia and heart failure(HF)during 6 months of follow-up was recorded.Results There were significant differences in two sets of MET value groups,time points,and group time point interactions(P＜0.01).No statistical difference was found in MET values be-tween the two groups before intervention(P＞0.05).The MET values were increased in both groups at 4,8 and 12 weeks after intervention than before intervention,and those in the study group were higher than those in the control group at above three time points(P＜0.05).Com-pared with before intervention,the peak oxygen uptake and anaerobic threshold oxygen uptake in 2 groups increased after intervention(P＜0.05).The peak oxygen uptake and anaerobic threshold oxygen uptake in the study group were higher than those in the control group[(23.52±1.86)ml/(min·kg)vs(21.36±2.60)ml/(min·kg),P＜0.01;(14.33±2.02)ml/(min·kg)vs(12.08±1.76)ml/(min·kg),P＜0.01];Compared with before intervention,the carbon dioxide ventilation equivalent slope of 2 groups decreased after intervention(P＜0.05).The carbon dioxide equivalent slope of the study group was lower than that of the control group(26.12±2.34 vs 28.10±2.52,P＜0.01).Compared with before intervention,the MIDAS score was decreased in both groups af-ter intervention(65.30±5.20 vs 96.64±7.33,P＜0.01;70.46±5.87 vs 95.80±7.26,P＜0.01),and the score of the study group was lower than that of the control group(65.30±5.20 vs 70.46±5.87,P＜0.01).After a 6-month follow-up,there was no significant difference in the incidence of adverse cardiovascular events between the two groups(P＞0.05).Conclusion Progressive reha-bilitation interventions based on the FITT principle can promote exercise tolerance,improve car-diopulmonary reserve function,and enhance the quality of life of elderly STEMI patients after PCI.

Objective:To identify the Key genes in the development of sepsis through weighted gene co-expression network analysis (WGCNA).Methods:The gene expression dataset GSE154918 was downloaded from the public database Gene Expression Omnibus (GEO) database, which containes data from 105 microarrays of 40 control cases, 12 cases of asymptomatic infection, 39 cases of sepsis, and 14 cases of follow-up sepsis. The R software was used to screen out differentially expressed genes (DEG) in sepsis, and the distributed access view integrated database (DAVID), search tool for retrieval of interacting neighbouring genes (STRING) and visualization software Cytoscape were used to perform gene function and pathway enrichment analysis, Protein-protein interaction (PPI) network analysis and key gene analysis to screen out the key genes in the development of sepsis.Results:Forty-six candidate genes were obtained by WGCNA and combined with DEG expression analysis, and these 46 genes were analyzed by gene ontology (GO) and Kyoto City Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to obtain gene functions and involved signaling pathways. The PPI network was further constructed using the STRING database, and 5 key genes were selected by the PPI network visualization software Cytoscape, including the mast cell expressed membrane protein 1 gene (MCEMP1), the S100 calcium-binding protein A12 gene (S100A12), the adipokine resistance factor gene (RETN), the c-type lectin structural domain family 4 member gene (CLEC4D), and peroxisome proliferator-activated receptor gene (PPARG), and differential expression analysis of each of these 5 genes showed that the expression levels of the above 5 genes were significantly upregulated in sepsis patients compared with healthy controls.Conclusion:In this study, 5 key genes related to sepsis were screened by constructing WGCNA method, which may be potential candidate targets related to sepsis diagnosis and treatment.

Objective:To investigate the relationship between SNP and noise-induced hearing loss (NIHL) susceptibility in occupational noise exposure population in China.Methods:From 6297 for a certain steel works in contact with noise, contact length of 3 years or more and workplace noise exposure intensity of 80 dB (A) , ears or high frequency (3 000, 4 000, 6 000 Hz) average of hearing acuity 40 dB (HL) , or high frequency loss in both ears, on the basis of single whisper frequency (500, 1, 000, 2 000 Hz) average threshold of 26 dB (HL) or object as case group. A case-control study was designed with 1:1 matching. Subjects with the same gender, the same type of work, age ±5 years old, and working age ±2 years after noise exposure were selected as the control group. Subjects with any whisper frequency (500, 1, 000, 2, 000 Hz) whose hearing threshold in any frequency band was ≤25 dB (A) and whose average high-frequency hearing threshold in pure tone hearing test was <35 dB (A) were selected as the control group. Four sites of PON2 gene were genotyped by medium-and high-throughput SNP genotyping. Univariate logistic regression was used to analyze the relationship between single SNP polymorphism and NIHL.Results:A total of 286 case-control pairs were included. Smoking was statistically significant difference between cases and controls ( P<0.001) . Conclusion:No statistical difference has been found between single SNP polymorphism and NIHL. At the level of greater than 92 dB of high noise exposure, rs7785846 (CT+TT) genotype is a risk factor for occupational noise deafness, and its OR is 2.74 (95% CI: 1.09-6.89) compared with wild homozygous type (CC) . Conclusion. The rs7785846 (CT+TT) genotype carriers of PON2 gene are more susceptible to hearing impairment when exposed to high noise intensity.

Objective:To investigate the relationship between SNP and noise-induced hearing loss (NIHL) susceptibility in occupational noise exposure population in China.Methods:From 6297 for a certain steel works in contact with noise, contact length of 3 years or more and workplace noise exposure intensity of 80 dB (A) , ears or high frequency (3 000, 4 000, 6 000 Hz) average of hearing acuity 40 dB (HL) , or high frequency loss in both ears, on the basis of single whisper frequency (500, 1, 000, 2 000 Hz) average threshold of 26 dB (HL) or object as case group. A case-control study was designed with 1:1 matching. Subjects with the same gender, the same type of work, age ±5 years old, and working age ±2 years after noise exposure were selected as the control group. Subjects with any whisper frequency (500, 1, 000, 2, 000 Hz) whose hearing threshold in any frequency band was ≤25 dB (A) and whose average high-frequency hearing threshold in pure tone hearing test was <35 dB (A) were selected as the control group. Four sites of PON2 gene were genotyped by medium-and high-throughput SNP genotyping. Univariate logistic regression was used to analyze the relationship between single SNP polymorphism and NIHL.Results:A total of 286 case-control pairs were included. Smoking was statistically significant difference between cases and controls ( P<0.001) . Conclusion:No statistical difference has been found between single SNP polymorphism and NIHL. At the level of greater than 92 dB of high noise exposure, rs7785846 (CT+TT) genotype is a risk factor for occupational noise deafness, and its OR is 2.74 (95% CI: 1.09-6.89) compared with wild homozygous type (CC) . Conclusion. The rs7785846 (CT+TT) genotype carriers of PON2 gene are more susceptible to hearing impairment when exposed to high noise intensity.

This study aimed to investigate the prevalence and molecular characteristics of Listeria monocytogenes in cooked products in Zigong City, China. The overall occurrence of the L. monocytogenes in the ready-to-eat (RTE) shops and mutton restaurants surveyed was 16.2% (141/873). An occurrence of 13.5% was observed in RTE pork, 6.5% in RTE vegetables, and more than 24.0% in either cooked mutton or cooked haggis. Serotype 1/2b (45.4%), 1/2a (33.3%), and 1/2c (14.2%) were the predominant types. By comparing the clonal complexes (CCs) based on multilocus sequence typing (MLST) of the L. monocytogenes from cooked foods in Zigong City and 33 listeriosis cases from different districts of China, CC87, CC9, CC8, and CC3 were showed to be prevalent in cooked products and CC87 and CC3 were the first two frequent types in the 33 clinic-source strains. All CC87 stains harbored the newly reported Listeria pathogenicity island 4 (LIPI-4) gene fragment ptsA, and all CC3 strains possessed the Listeria pathogenicity island 3 (LIPI-3) gene fragment llsX. These may increase the occurrence of the strains belonging to CC87 and CC3 in listeriosis cases in China and also underline the risk of infection owing to the consumption of the cooked products from Zigong. ST619 (serotype 1/2b) harbored both llsX and ptsA, indicating a potential hypervirulent sequence type in Zigong.
China ; epidemiology ; Cooking ; Fast Foods ; microbiology ; Food Contamination ; Food Microbiology ; Humans ; Listeria monocytogenes ; genetics ; pathogenicity ; Listeriosis ; epidemiology ; microbiology ; Meat ; microbiology ; Multilocus Sequence Typing ; Prevalence ; Seasons

Objective To investigate the risk factors of bladder spasm after transurethral resection of the prostate (TURP) and the intervention effect of cluster nursing. Methods From January 2011 to December 2012, the clinical data of 120 cases of TURP patients were analyzed for the risk factors of bladder spasm after TURP. According to the results of the analysis, cluster nursing plan was constructed. The 150 TURP patients from January 2013 to December 2014 were selected as the control group and given routine nursing care. The 150 TURP patients from January 2015 to December 2016 were recruited as the observation group and given cluster nursing. The postoperative bladder spasm, catheter blockage and patients satisfaction were compared between the two groups. Results The results of the multivariate regression analysis indicated that the score of Self-rating Anxiety Scale, air bag water injection, unstable bladder or low compliance bladder, and postoperative constipation were independent factors of bladder spasm after TURP (OR=1.427, 0.092, 13.263, 27.437; P<0.01). After the implementation of cluster nursing, the postoperative bladder spasm rate was 6.0%, and the catheter blockage rate was 5.3%, which were both lower than those of the control group (28.4%,29.3%), and the differences were statistically significant (χ2=25.726, 30.149; P<0.01). The patient postoperative satisfaction of the observation group was (95.21±4.63), which was higher than that of the control group (85.76±4.23), and the difference was statistically significant (t=14.469, P<0.01). Conclusions Cluster nursing can reduce the rate of bladder spasm and catheter blockage after TURP, and increase patients' satisfaction after surgery.

An ultrasensitive electrochemical immunosensor modified with graphene and dienestrol(DE)was developed for the detection of dienestrol through indirect competition with K3Fe(CN)6 acting as the redox probes. The results revealed that under optimized conditions a calibration for DE was obtained with a linear range of 500-5 000 ng/mL and the detection limit was up to 0. 2 ng/mL, showing that the proposed electrochemical immunosensor had excellent sensitivity and wide detection range. The immunosensor was examined in real samples for the analysis of DE. A good recovery in the range of 83. 8%-97. 7% was obtained in pork samples.