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 observe the uric acid-lowering effect of 3,4-dihydroxy-5-nitrobenzaldehyde (DHNB) on hyperuricemia models in mice and quails so as to improve the pharmacodynamic validation on hyperuricemia models. 【Methods】 The mouse hyperuricemia animal model was prepared by intraperitoneal injection of potassium oxonate 300 mg/kg; 30 g/(kg·d) yeast powder mixed feed (yeast powder∶feed, 1∶4) was used to prepare the quail hyperuricemia animal model. DHNB, 100 mg/kg, was intraperitoneally injected into the mice 1 hour prior to modeling; DHNB, 100 mg/kg, was intragastrically administered for two days consecutively into the quail hyperuricemia models. Control groups in mice and quails were set up respectively. Biochemical kits were used to detect serum uric acid, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), creatinine (Cr), and blood urea nitrogen (BUN) in mouse and quail serum. Heart, lung, liver and kidney tissues of mice and quails were stained with HE. 【Results】 The serum uric acid in the mouse and quail hyperuricemia model groups was higher than that in the control group [(277.37±94.89) μmol/L vs. (176.49±44.83) μmol/L, P<0.05; (313.58±191.87) μmol/L vs. (167.26±66.56) μmol/ L, P<0.05)], indicating that the modeling was successful. DHNB could not reduce serum uric acid in hyperuricemia mouse model [(277.37±94.89) μmol/L vs. (238.72±63.43) μmol/L, P>0.05]. However, it significantly decreased serum uric acid in the quail model of hyperuricemia (313.58±191.87) μmol/L vs. (160.44±49.90)μmol/L, P<0.05]. Administration of DHNB 100 mg/kg one or two times had no effect on the liver and kidney functions of mice and quails, and had no toxicity to the heart, lung, liver or kidney tissues of mice and quails. 【Conclusion】 DHNB has a uric acid-lowering effect on the hyperuricemia quail model, and a single dose that caused the uric acid-lowering effect has no obvious toxicity to mouse or quail viscera. The quail hyperuricemia model is more suitable for the validation of the uric acid-lowering efficacy of DHNB than the mouse hyperuricemia model.

Objective To investigate the prevalence of soil-transmitted nematode human infections in Jurong City from 2016 to 2020, so as to provide the scientific evidence for formulating the control strategy. Methods During the period from 2016 to 2020, the permanent residents at ages of over 3 years living in Jurong City were selected as the study subjects. Stool samples were collected for the detection of soil-transmitted nematode eggs using the modified Kato-Katz thick smear method (two detections for one stool sample), and the species of hookworm was identified in stool-positive stool samples using the culture method. The prevalence and intensity of soil-transmitted nematode infections were calculated, and the change of the infection prevalence among years was examined using the Cochran-Armitage test for trend. Results A total of 10 011 people-time populations were detected for soil-transmitted nematode infections in Jurong City from 2016 to 2020, and 56 egg-positives were identified, with mean prevalence of 0.56%. The prevalence of soil-transmitted nematode human infections appeared a tendency towards a decline year by year in Jurong City (χ²_trend = 5.15, P < 0.01). The mean prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura infections was 0.44%, 0.11% and 0.20% in Jurong City from 2016 to 2020, respectively, and individuals with hookworm infections accounted for 78.57% of all cases with soil-transmitted nematode infections. Single parasite (98.21%) and mild infection were pre-dominant in individuals with soil-transmitted nematode infections, and no multiple infections were seen after 2016. Conclusions The prevalence of human soil-transmitted nematodiasis is low in Jurong City. Based on reinforcement of soil-transmitted nematodiasis surveillance, an increase in the health education investment is required to consolidate the control achievements.

The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and β2-microglobulin(β2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine β2-MG and interleukin-1β(IL-1β) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1β levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 μg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 μg·mL~(-1) FHT). After 24 h incubation, the level of IL-1β in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and β2-MG levels in serum and β2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1β in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1β, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1β, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.
Animals ; Drugs, Chinese Herbal ; Hyperuricemia/drug therapy* ; Kidney ; Male ; Mice ; Uric Acid

Objective To understand the endemic situation and control effect of schistosomiasis through the surveillance in a national surveillance site of Jurong City, so as to provide the evidence for formulating the prevention and control measures. Methods According to the National Schistosomiasis Monitoring Scheme (2014 Edition), the surveillance of schistosome infection in Oncomelania hupensis snails, residents and livestock was performed in the Kongqing Village, a national surveillance site of Jurong City, from 2015 to 2017. Results The areas with snails were 0, 0, and 0.63 hm² in 2015, 2016, and 2017 respectively; the average densities of living snails were 0, 0, and 0.19 snails/0.1 m² in 2015, 2016, and 2017 respectively. No schistosome-infected snails were found. The positive rates of blood tests for schistosomiasis in the local residents were 7.72%, 7.45% and 3.45%, and the positive rates of blood tests in the floating population were 4.90%, 3.47% and 0.97% in 2015, 2016 and 2017, respectively. No positives were found in the schistosome etiology detection in the crowd and livestock. Conclusions The effect of schistosomiasis prevention and control is obvious in Jurong City, but O. hupensis snails are still of recurrence. Therefore, the monitoring and control efforts should be strengthened to consolidate the achievements of schistosomiasis prevention and control.

Aim To explore the mechanism of insulin in combination with selenium preventing myocardial apoptosis in diabetic cardiomyopathy rats .Methods SD rats ( n =50 ) were randomly divided into five groups: control , diabetic cardiomyopathy ( DCM ) , DCM with insulin treatment , DCM with selenium treat-ment, and DCM with insulin and selenium combination treatment .The cell apoptosis was observed by TUNEL . The levels of Bcl-2, caspase-3, PARP, Cbl-b and p38 MAPK were examined by Western blot .The inter-actions of Cbl-b-p38 MAPK and Ku70-Bax were detec-ted by immunoprecipitation .Results Insulin in com-bination with selenium synergistically inhibited apopto-sis, up-regulated Cbl-b, down-regulated p38MAPK ex-pressions and increased the interactions of Cbl-b-p38MAPK and Ku70-Bax.Conclusion Insulin and selenium synergistically inhibit myocardial apoptosis by regulating Cbl-b-inhibited p38 MAPK and preventing Bax translocation .

AIM:To investigate the effect of insulin and selenium in combination on the apoptosis and the ex-pression of Ku70, acetylated Ku70, Bax and cytochrome C in myocardial cells of the rats with diabetic cardiomyopathy (DCM), and to explore the mechanism of insulin and selenium in their synergistic anti-DCM effect.METHODS:SD rats (n=50) were randomly grouped into control, DCM, DCM with insulin treatment (DCM+In) group, DCM with selenium treatment (DCM+Se) group, and DCM with insulin and selenium combination treatment (DCM+In+Se) group.Mito-chondrial membrane potential ( MMP) was measured by flow cytometry .The cell apoptosis was observed by terminal-deoxy-nucleotidyl transferase mediated nick end labeling (TUNEL).The levels of Ku70, Bax and cytochrome C were examined by Western blot .The acetylation status of Ku 70 was detected by co-immunoprecipitation .RESULTS: The rats in DCM group showed marked cell apoptosis compared with the control rats .The levels of Ku70 and acetylated Ku70 declined sig-nificantly compared with control group .Bax significantly translocated from cytoplasm into mitochondria and cytochrome C translocated from mitochondria into cytoplasm compared with control group .Compared with DCM +In group or DCM +Se group, insulin and selenium in combination significantly inhibited the apoptosis , down-regulated Ku70 and acetylated Ku70 levels, and prevented Bax and cytochrome C translocation .CONCLUSION: Insulin and selenium synergistically inhibits myocardial apoptosis by regulating Ku 70 acetylation and inhibiting Bax translocation .

[ABSTRACT]OBJECTIVETo investigate the phoenix roebelenii pollen as the allergen of allergic rhinitis in Hainan Province and provide guidance for prevention and treatment of allergic rhinitits.METHODSA total of 2054 patients with allergic rhinitis were tested with the allergen of phoenix roebelenii pollen by skin prick test, and then choose 30 positive cases to give the nasal mucosa provocation test. RESULTSThe total positive rate of allergen of phoenix roebelenii pollen by skin prick test was 67.38% (1384/2054). The 30 cases with positive skin prick test were all positive in nasal mucosa provocation test and the cases in control group were all negative.CONCLUSIONPhoenix roebelenii pollen is an important allergen in Hainan Province. There is a correlation between skin prick test and nasal mucosa provocation test. The allergen skin prick test can provide clue for the patients to avoid the pathogenic allergens and for the specific immunotherapy.

Objective:To explore the interaction between gossypol and human serum albumin ( HSA) . Methods:The interaction of gossypol and HSA under physiological conditions was studied by fluorescence spectroscopy, and the molecular docking software was used to simulate the interaction. Results:The binding constant of gossypol and HSA at 293K and 303K was 2. 390 6 × 105 L·mol-1 and 3. 576 8 × 103 L·mol-1 , respectively. There was one binding site on HSA for gossypol. Hydrogen bond and Van Der Waals inter-actions were involved in the binding process. The binding of gossypol and HAS was closer to tyrosine residue in HSA. The molecular simulation analysis verified the above results. Conclusion: The gossypol-induced fluorescence quenching of HSA belongs to a static quenching procedure.

Objective To investigate the community residents′ perceptions of community health policy and the learning ways, and further analyze the main influencing factors, so as to effectively promote for the community health policy. Methods Using multiple stage, a total of 542 community residents were investigated by questionnaire including general information, cognitive status of health policy and ways of cognition, and the Cronbach′s αcoefficient and rates coefficient were 0. 82 and 0. 91. Results The average age of 542 community residents was (46. 0 ± 15. 4) years, and 25. 8% (140/542) and 70. 5% (382/542) community residents did not understand health policy completely or understood part of health policy. The cognitive ways of community residents acquired the health policy including TV/internet 60. 0%, news paper/magazine 31. 5%, wall poster 24. 9%, and others 20. 3%. The education background, occupation and so on influencing factors affected the cognitive status of health policy among community residents. Compared with female, male preferred to acquired health policy for wall poster;residents, who came from countryside and was beyond 60 years old, would like to obtain it from community health workers and other ways. Conclusions The cognitive status of health policy requires improving among community residents. We should promote the cognition of health policy in community residents according to the influencing factors and learning ways of health policy.