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.

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.

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 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.

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.

ObjectiveThe study of the treatment of hypertriglyceridemia with scutellaria baicalensis stem-leaf total flavonoid (SSTF) are rarely reported.The objective of this study is to investigate the effects of SSTF on lipid metabolism and oxidative stress in rats with hypertriglyceridemia.Methods60 SD rats were randomly divided into normal group, model group, fenofibrate group (100 mg·kg-1), SSTF groups with low, medium and high doses (50,100,200 mg·kg-1, respectively). All rats, except those of the normal group, were fed with high-fat diet and given corresponding drug intervention for 6 weeks. Then the body masses at the 2nd, 4th and 6th weeks as well as wet weight of the liver at the end of 6th week were recorded, and liver index was calculated. The serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected. The levels of TG, TC, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver tissue were determined, and liver histopathological changes were observed by hematoxylin-eosin (HE) staining.ResultsIn the model group, compared with the normal group, the body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week were increased, the serum levels of TG, TC and LDL-C got increased with decreased HDL-C level, and the levels of TG[（1.603±0.146）mmol/L], TC[（3.474±0.356）mmol/L] and MDA[（10.288±1.979）nmol/mg] in liver tissue were increased with decreased levels of SOD[（106.840±24.014）U/mg] and GSH-PX[（9.278±2.079）U/mg]. Compared with the model group,the fenofibrate group and all SSTF groups showed decreased body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week, decreased serum levels of TG, TC and LDL-C with increased level of HDL-C, and decreased levels of TG, TC and MDA with increased levels of SOD and GSH-PX in liver tissue. The comparsion between the fenofibrate group and the high-dose SSTF group revealed that the body masses at the 4th and 6th weeks and liver index at the end of 6th week were decreased, the serum levels of TG, TC and LDL-C were decreased with increased level of HDL-C, and the levels of TG[（0.718±0.135）mmol/L] and MDA[（5.071±1.305）nmol/mg] in liver tissue got decreased with increased levels of SOD[（172.210±30.214）U/mg] and GSH-PX[（14.623±2.418）U/mg] in the latter group. All the above-mentioned differences were statistically significant (all P<0.05).ConclusionSSTF can regulate lipid metabolism and improve pathological injury of liver in hypertriglyceridemia rats, which may be related with inhibition of lipid peroxidation and reduction of oxidative stress.