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

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective To observe the expression and forewarning effect of MiR-155-5p in the chronicity process of herpes zoster neuralgia (HZN).Methods A total of 88 patients with herpes zoster neuralgia (HZN group) and 20 healthy subjects undergoing physical examination (HA group) were selected.The expression level of serum miR-155-5p was measured by reverse transcription real-time fluorescence quantification poly-merase chain reaction (RT-qPCR).The patients with pain after 3-month follow up served as herpes zoster neuralgia (PHN group) and those with pain disappearance served as the cure group (RC group).The expres-sion levels of miR-155-5p were compared between the HZN group and HA group and between the PHN group and RC group.The area under receiver operating characteristic (ROC) curve (AUC) and 95％ confidence in-terval (CI) were calculated for evaluating the efficiency of miR-155-5p in predicting the chronicity of HZN. Results Compared with the HA group,the expression level of miR-155-5p in the HZN group was significant-ly up-regulated,and the difference was statistically significant (P<0.05);compare with the RC group,the ex-pression level of serum miR-155-5p in the PHN group was significantly up-regulated,and the difference was statistically significant (P<0.05);AUC of miR-155-5p for predicting the chronicity of HZN was 0.878 (95％CI:0.808-0.948).Conclusion The expression level of serum miR-155-5p in herpes zoster period of the pa-tients with PHN is significantly up-regulated compared with the cure patients and miR-155-5p could serve as an important predictive indicator of HZN chronicity.

This study was designed to investigate the biological function and interaction mechanism of deubiquitinating enzyme USP14 and β-catenin in endometrial carcinoma(EC).The expression of USP14 and β-catenin in EC tissues and adjacent healthy tissues were detected by real-time fluorescence quantitative PCR and immunohistochemistry,while the effects of USP14 on β-catenin protein stability and ubiquitination were investigated by Western blotting and protein immunoprecipitation using HEA-1C and Ishikawa cell lines derived from EC.The effect of USP14 and β-catenin on EC cell proliferation was verified by cell proliferation assay(CCK-8);the regulatory effect of USP14 on β-catenin was verified by plasmid transfection.The regulation of USP14 and β-catenin on the expression of proteins related to epithelial-mesenchymal transition(EMT)in EC cells were verified by Western blotting.Data showed that the expression of USP14 and β-catenin in EC tissues were higher than those in adjacent healthy tissues,and USP14 and β-catenin interacted in EC cell line.USP14 maintained the protein stability of β-catenin through its deubiquitination activity.USP14-specific inhibitors could enhance the ubiquitination level of β-catenin and down-regulate the expression of β-catenin.USP14-specific inhibitors also inhibited EC cell proliferation and inhibited the expression of EMT-related proteins,while overexpression of β-catenin reversed the inhibition of EC cell growth and EMT induced by USP14 inhibitors.In conclusion,USP14 maintains β-catenin protein stability in EC cells by regulating the ubiquitination level,and the regulation of cell proliferation and EMT requires β-catenin.

This study was designed to investigate the biological function and interaction mechanism of deubiquitinating enzyme USP14 and β-catenin in endometrial carcinoma(EC).The expression of USP14 and β-catenin in EC tissues and adjacent healthy tissues were detected by real-time fluorescence quantitative PCR and immunohistochemistry,while the effects of USP14 on β-catenin protein stability and ubiquitination were investigated by Western blotting and protein immunoprecipitation using HEA-1C and Ishikawa cell lines derived from EC.The effect of USP14 and β-catenin on EC cell proliferation was verified by cell proliferation assay(CCK-8);the regulatory effect of USP14 on β-catenin was verified by plasmid transfection.The regulation of USP14 and β-catenin on the expression of proteins related to epithelial-mesenchymal transition(EMT)in EC cells were verified by Western blotting.Data showed that the expression of USP14 and β-catenin in EC tissues were higher than those in adjacent healthy tissues,and USP14 and β-catenin interacted in EC cell line.USP14 maintained the protein stability of β-catenin through its deubiquitination activity.USP14-specific inhibitors could enhance the ubiquitination level of β-catenin and down-regulate the expression of β-catenin.USP14-specific inhibitors also inhibited EC cell proliferation and inhibited the expression of EMT-related proteins,while overexpression of β-catenin reversed the inhibition of EC cell growth and EMT induced by USP14 inhibitors.In conclusion,USP14 maintains β-catenin protein stability in EC cells by regulating the ubiquitination level,and the regulation of cell proliferation and EMT requires β-catenin.

Objective:To determine the median effective dose(ED 50) of alfentanil combined with propofol inhibiting responses to the laryngeal mask airway(LMA) insertion in children. Methods:American Society of Anesthesiologists Physical Status classification Ⅰ children, aged 6-10 yr, with body mass index of 18-24 kg/m 2, undergoing facial skin pigmented nevus resection, were selected. Propofol(target plasma concentration 3 μg/ml) was given by the target-controlled infusion, alfentanil was intravenously injected, 2 min later LMA was inserted, and anesthesia was maintained with 2%-3% sevoflurane until the end of surgery. The dose of alfentanil was determined by the up-and-down sequential method, the initial dose of alfentanil was 15 μg/kg, when the response to LMA insertion was positive/negative, the dose of alfentanil increased/decreased by 1 μg/kg in the next case. The LMA insertion response was defined as swallowing, bucking, body movement occurred during insertion of the LMA, and this process was repeated until 7th turning points appeared. The ED 50 and 95% confidence interval of alfentanil combined with propofol inhibiting responses to LMA insertion in children were calculated using probit method. Results:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion was 13.18(95% confidence interval 12.43-13.79) μg/kg in children. Conclusions:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion is 13.18 μg/kg in children.

OBJECTIVE To analyze the patents of new target oral drugs for type 2 diabetes mellitus （T2DM）， and to provide references for the research and development direction and patent layout of new domestic diabetes drugs. METHODS Based on global patent data in the HimmPat database， from multiple perspectives such as the number of patent applications and authorization， development trend， regional distribution and main applicants， statistics and analysis were performed for the patents related to 3 types of new target oral drugs for T2DM， such as glucokinase activator （GKA）， protein tyrosine phosphatase 1B inhibitor （PTP-1B-IN）， and 11β-hydroxysteroid dehydrogenase 1 inhibitor （11β-HSD1-IN）. RESULTS & CONCLUSIONS A total of 1 649 patents of GKA， 709 patents of PTP-1B-IN， 592 patents of 11β-HSD1-IN were obtained， the main applicants were well-known pharmaceutical companies， which possessed the core patents of pharmaceutical compounds. The research on GKA drugs was more mature， with a larger number of patent applications and a more comprehensive enterprise layout. Domestic enterprises， universities and research institutions had advantages in the field of PTP-1B-IN. Domestic enterprises and research institutions can leverage the advantages of traditional Chinese medicine and resources to enhance their research capabilities and improve technological competitiveness through core technology exploration， the exploration of process route， patent layout， industry- university-research cooperation and the establishment of patent pool.

Objective:To determine the value of ultrasonographic measurement of submental soft tissue distance in predicting poor ventilation with laryngeal mask airway (LMA).Methods:A total of 272 American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 25-78 yr, weighing 40-85 kg, with mechanical ventilation time 30-120 min, scheduled for elective lower limb vascular surgery or lithotripsy under general anesthesia with LMA, were selected.The parameters of submental soft tissue of tongue thickness (TT), distance from skin to the hyoid bone (DSHB), distance from skin to epiglottis midway (DSEM) and distance from skin to anterior commissure of the vocal cords (DSAC) were measured using ultrasonography before operation.The type of LMA was chosen according to the instruction book.The development of failure of LMA placement at the first attempt, air leakage around LMA cuff during mechanical ventilation, peak airway pressure >20 cmH 2O and gastric insufflation detected by ultrasonography were recorded.The development of one or more adverse events mentioned above was considered to be poor ventilation.The patients were divided into normal ventilation group (N group) and poor ventilation group (P group) according to whether poor ventilation occurred.The receiver operating characteristic curve for ultrasonographic measurement of submental soft tissue distance in predicting poor ventilation with LMA was drawn, and the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity and cut-off value were calculated.The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factors for poor ventilation with LMA. Results:The AUC for TT, DSHB, DSEM and DSAC measured using ultrasonography in predicting poor ventilation with LMA (95%CI) was 0.866 (0.813-0.919), 0.755 (0.683-0.827), 0.835 (0.772-0.899) and 0.705 (0.628-0.782) ( P<0.05 or 0.01), respectively.The results of logistic regression analysis showed that TT≥6.140 cm, DSHB≥1.145 cm, DSEM≥2.175 cm and DSAC≥1.075 cm were risks factor for poor ventilation with LMA. Conclusion:Ultrasonographic measurement of TT, DSHB, DSEM and DSAC can predict the development of poor ventilation with LMA.

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