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 analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival.Methods:It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality.Results:A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions:The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Objective To explore the effect of gender,training duration and type of sports on electro-cardiographic changes in Chinese elite athletes by performing electrocardiography(ECG).Methods A to-tal of 891 Chinese elite athletes who underwent ECG examinations between 2016 and 2019 were in-cluded in the study.The ECGs were divided into three groups according to the guidelines of the Euro-pean Society of Cardiology(ESC)in 2010:group 0(normal ECG),group 1(common and training-relat-ed ECG)and Group 2(uncommon and training-unrelated ECG).The effect of gender,training dura-tion(4 to 6 years,7 to 10 years and more than 11 years)and sports types(skill,strength,endur-ance and mixed categories)on the ECG changes was assessed.Results No significant differences were found in Group 2 in sex,training duration or sports types.However,the prevalence of common train-ing-related ECG changes was significantly higher in male athletes than in female athletes(58.9%vs.47.4%).Moreover,the highest prevalence was found in athletes with more than 11 years of training,significantly higher than those with 4-6 years of training(P<0.05).A highly significant difference was also observed among athletes of different sports(P<0.01),with the highest in those of the mixed cate-gory at 64.6%.Moreover,sinus bradycardia occurred with significantly higher incidence in athletes un-dertaking mixed and endurance training than others(P<0.05).Conclusion The training-related ECG changes of Chinese elite athletes is closely correlated to their gender,training duration and sports types.

Chronic intestinal pseudo-obstruction is a serious intestinal dysmotility disorder with symptoms of bowel obstruction without mechanical obstruction.Compared with chronic intestinal pseudo-obstruction in adults, pediatric chronic intestinal pseudo-obstruction has unique clinical characteristics.Generally, 80% of pediatric chronic intestinal pseudo-obstruction cases are primary and idiopathic and there is no specific treatment, and management is mainly symptomatic.With the advancements in genetic testing, new findings have been identified, allowing for a better understanding of the underlying mechanisms of intestinal dysmotility and potential etiologies.This article reviews the genetic research progress of pediatric chronic intestinal pseudo-obstruction in recent years, introduces the pathological mechanism and clinical characteristics, and summarizes the pearls of diagnosis and treatment.

OBJECTIVE: To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint. METHODS: Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups. RESULTS: There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05). CONCLUSION Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.
Animals ; Humans ; Knee ; Knee Joint ; Menisci, Tibial/surgery* ; Swine ; Tendons ; Tibia

Objective:To investigate the correlations between expression of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1) and their functions on exosome secretion, proliferation and invasion in hepatocellular carcinoma (HCC).Methods:We used small interfering RNA of MALAT1 (si-MALAT1) to knockdown MALAT1 in HuH-7. At the meanwhile, cells which were transfected with si-NC were used as the negative control group. Expression of NEAT1, cell proliferation and invasion function were detected these two groups. HuH-7 cells were transfected with lentivirus NEAT1 over expressing vector (lv-NEAT1) or negative control (lv-control). Expression of exosomes secretion related genes were analyzed between lv-NEAT1 and lv-control groups. Cells of lv-NEAT1 were knockdown MALAT1 expression using si-MALAT1, which could be si-MALAT1+ lv-NEAT1 group. exosomes secretion was detected in si-NC, si-MALAT1 and si-MALAT1+ lv-NEAT1 group. We treated cells (si-MALAT1 group) with exosomes from cells with lv-NEAT1 or lv-control to divide cells as si-MALAT1+ exosomes of lv-NEAT1 cells and si-MALAT1+ exosomes of lv-control groups. Cell proliferation and invasion of cells were detected in two groups.Results:Low expression of NEAT1 were found in MALAT1 knockdown cells compared with si-NC group [(0.72±0.02) vs. (0.98±0.01), P<0.05]. Cells with MALAT1 knockdown shown diminished proliferation [(0.66±0.03) vs. (0.98±0.04), P<0.05)] and invasion [(88.33±7.26) vs. (147.70±13.62), P<0.05)]. Compared with si-NC group, CD9 and CD63 expression were decreased in exosomes of si-MALAT1 group. Compared with si-MALAT1 group, CD9 and CD63 expression was increased in exosomes of si-MALAT1+ lv-NEAT1 group. Compared with si-MALAT1+ exosomes of lv-control group, proliferation [(0.97±0.03) vs. (0.74±0.05), P<0.05)] and invasion [ (132.70±7.36) vs. (98.33±6.01), P<0.05) ] were increased in si-MALAT1+ exosomes of lv-NEAT1 group. Exosomes related genes expression including HSPA8 (5.53±0.31), SLC3A2 (0.32±0.07) and SLC7A5 (0.77±0.45) were changed in lv-NEAT1 group compared with lv-control group [(0.98±0.15), P<0.05]. Conclusion:MALAT1 induced exosomes secretion by NEAT1 and exosomes related genes regulation. This regulation might be related with increased proliferation and invasion function in HCC cells with MALAT1 and NEAT1 abnormal expression.

Objective:The underlying causes of unexplained syncope and palpitations are difficult to determine in clinical practice. This study was designed to investigate the value of the insertable cardiac monitor (ICM) for the diagnosis of the unexplained syncope and palpitations.Methods:A total of 184 patients with syncope or palpitations due to unexplained reasons were enrolled in the First Affiliated Hospital of Xinjiang Medical University (144 patients with unexplained syncope and 40 patients with unexplained palpitations) from October 2015 to October 2019. Among them, 99 patients (77 patients with unexplained syncope and 22 patients with unexplained palpitations) were received ICM implantation (the ICM implanted group) and 85 patients (67 patients with unexplained syncope and 18 patients with unexplained palpitations) were not (the non-ICM implanted group). The patients in the ICM implanted group were followed up once every 3 months until the occurrence of syncope or palpitations. During follow-up, the electrocardiograph (ECG) data recorded by ICM were collected and analyzed retrospectively. The patients in the non-ICM implanted group underwent routine follow-up.Results:The follow-up time of the ICM implanted group was (29.3±9.3) months, and the follow-up time of the non-ICM implanted group was (27.2±10.4) months. The total detection rate (syncope and palpitations) in the implanted ICM group was much higher than that in the non-ICM implanted group (38.4% vs. 3.5%, P<0.001), with syncope detection rate of 40.3% in the implanted ICM group and 3.0% in the non-ICM implanted group ( P<0.001), and palpitation detection rate of 31.8% in the implanted ICM group and 5.6% in the non-ICM implanted group ( P<0.05). Conclusions:Application of ICM greatly improved the diagnosis rate of patients with unexplained syncope and palpitations. It is recommended for patients with unexplained syncope and palpitations to implant ICM as soon as possible.

Objective:To investigate the emergency treatment and clinical effect when the guidewire stuck in the right atrium during central vein catheter placement for hemodialysis.Methods:Five cases with guidewire stuck in the right atrium during central vein catheter placement for hemodialysis from January 2011 to July 2018 admitted into the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. In two cases, the guidewires were found completely stuck when the insert depth was about 20 cm. The guidewires were not able to move forward nor backward. In the other three cases, the guidewires could be moved forward but not backward with the insert depth at about 18 cm. All patients received emergent computed tomography angiography (CTA) or digital subtraction angiography (DSA) imaging. Images showed that the guidewires were stuck in the right atrium near the ventricular valve. The guidewire core drawing method, the multipurpose angiography(MPA) catheter capturing method and the manual guidewire adjusting method were used for emergent treatment.Results:One patient with completely stuck guidewire was successfully treated with guidewire core drawing method and the temporary central vein catheter catheterization through the internal jugular vein was performed under DSA. In a completely stuck case and a retrogradely stuck case, the J-shaped ends of the warped guidewires were captured into the MPA catheter, and the guidewires were then withdrawn from right atriums along with the contrast catheter. In the other 2 retrogradely stuck cases, under DSA, the guidewires were repeatedly pushed, the direction of J-shaped ends was manually adjusted, and then the guidewires were repeatedly pushed and pulled until catheters can be pulled out of the right atriums. The later 4 cases had permanent central vein catheter placement with the same guidewire after the stuck guidewires were withdrawn from the right atrium and readjusted.Conclusions:All three methods can successfully solve the emergent situation of the stuck guidewire in the right atrium. For patients with completely stuck guidewires, the MPA catheter capturing method can be simpler, safer, and more effective.

Objective To investigate the application of percutaneous transluminal balloon dilatation (PTA) in catheter replacement within patients with catheter-related central vein disease (CVD). Methods Thirteen cases of CVD patients from Jan 2015 to Mar 2018 admitted into the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. All of them underwent digital subtraction angiography (DSA) to clarify problem origin. Suitable balloons were chosen to dilate the original catheters or the occlusive veins, and then the original catheters were replaced. PTA was used to help catheter replacement and all patients were followed up for 6 months. Results Four of the 13 patients were found stuck when replacing catheters. All of them successfully had catheters removed with PTA (Hong's techniques). All patients had successfully catheter replacement with blood flow volume>250 ml/min. Among 4 patients with edema, 3 patients showed better within 6 months. Only 3 patients needed warfarin to keep blood flow volume>250 ml/min within 6 months. Conclusions PTA shows advantages of lesser trauma, better tolerance and higher success rate in patients with catheter-related CVD. It can also relieve symptoms resulting from occlusive central vein.