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.

Acute kidney injury(AKI)is a reversible but may be a life-threatening condition,can be caused by a variety of reasons.The immune system plays a key role in the pathology of AKI because its response to the injury includes an inflammatory response that may further damage renal tissue.Inflammatory cell death(PANoptosis)pathway in the process of immune response is activated and leads to the release of pro-inflammatory cytokines and further tissue damage.In this study,mononuclear RNA sequencing data from the NCBI Gene Expression Omnibus(GEO)public database were used to analyze gene expression differences between acute kidney injury(AKI)and normal kidney tissues.The cell clusters of AKI and normal group were annotated to identify and extract the immune cells;hub genes adjusting PANoptosis were screened and verified by RT-qPCR.So as to evaluate the interaction and mechanism of immune cells in proinflammatory responses inducing cell death in AKI.Finally,an interaction network of 12 hub genes was constructed,which provides a solid foundation for further investigation of the detailed mechanisms by which immune cells regulate cell death in AKI and opens insights into potential therapeutic target strategies.The expression levels of five genes(JUN,IL1RAP,PIK3R1,IRAK3,NLRP3)in the AKI group were significantly higher than those in the NC group.In addition,we have identified and defined a novel inflammatory proximal flexotubular cell and suggest future intensive investigation on this cell subtype in AKI,as they may play an important role in the pathological process of AKI and could be a potential target for therapy.As a conclusion,there are 12 hub genes that interact with each other and play a role in the regulation of cell death in AKI immune cells.A novel class of inflammatory proximal convoluted tubule cells are identified and defined,which play an important role in the pathological process of AKI and may be a potential target for therapy.

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 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 investigate the correlation between body mass index and the increase in body mass during pregnancy and adverse pregnancy outcomes in elderly pregnant women. Methods The clinical data was collected from 1,374 pregnant women who underwent regular prenatal care checkups and delivered a child at Jiangsu Maternity and Child Health Hospital from January 1, 2020 to May 1, 2020. According to the age of pregnant women, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG), the subjects were divided into different groups. The incidence of adverse pregnancy outcomes between groups was compared, and the correlation between pregnant women's age, pre-pregnancy BMI and GWG and adverse pregnancy outcomes was analyzed. Results Compared with the non-advanced age group, the elderly group had an increase in the incidence rate of gestational diabetes (GDM) (38.66% VS 19.54%), the incidence rate of large for gestational age (LGA) (LGA) (19.75% VS 14.43%), and the cesarean section rate (55.46% VS) 34.77%), and the differences between the groups were statistically significant (t=40.773, 4.270, 35.630, P=0.001, 0.039, 0.001). There were no significant differences between the non-advanced age group and the elder group in the incidence of pregnancy-induced hypertension (PIH) (10.92% VS 8.63%), the incidence of small for gestational age (2.52% VS 2.90%), and the incidence of neonatal asphyxia ( 2.10% VS 1.23%) (t=1.265, 0.105, 1.088, P=0.261, 0.746, 0.297). ). The incidence of GDM in overweight and obese elderly pregnant women was higher than that in underweight and normal pregnant women. The incidence of GDM in the elderly pregnant women with less GWG and excessive GWG was higher than that in the normal group (P<0.05). Conclusion The pre-pregnancy body mass index and the gain in body mass during pregnancy are related to the occurrence of adverse pregnancy outcomes. It is necessary to strengthen the monitoring and management of pre-pregnancy body mass index and pregnancy body quality in elderly pregnant women.

Objective To characterize the biomarkers of urine samples for early diagnosis of colorectal cancer(CRC)using proton nuclear magnetic resonance (1H-NMR)combined with pattern recognition.Methods 400 MHz 1H-NMR was used to test the urine samples obtained from 23 patients with Ⅰ/Ⅱ stage CRC,40 healthy controls (HC)and 18 patients with esophageal cancer (EC). Pattern recognition through orthogonal partial least squares-discriminant analysis (OPLS-DA)was applied on 1H-NMR data to find urine metabolic differences between CRC and HC.Results OPLS-DA could effectively determine HC,patients withⅠ/Ⅱstage CRC and patients with esophageal cancer.Compared with HC,early stage CRC had significant decreases of choline,isocitric acid,lactamine,phenylalan, cysteine,creatinine,aspartic acid,hippurate acid,methylamine,dimethyl sulfone,and increases of acetoacetate,glutamine,glycocyamine,cis-aconitate, trans-aconitate,homocycteine in the urine samples.Conclusion Urine metabonomics based on NMRIndicates that glucose metabolism,amino acid metabolism,choline metabolism,energy metabolism and intestinal microflora are disturbance in colorectal cancer patients,which provide valuable metabolic information on the molecular level for early diagnosis of colorectal cancer.

Objective To characterize the metabolic "fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer (CRC) using proton nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics coupled with pattern recognition.Methods From January 2014 to December 2014,we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College,from 25 patients with colorectal adenomas (CR-Ad),20 with stage Ⅰ /Ⅱ CRC,and 32 healthy controls (HCs).The patients were diagnosed by histopathology.No subjects had any complicating diseases.HCs showed no abnormalities from blood tests,endoscopic examination,diagnostic imaging,and/or medical interviews.We excluded participants who used antibiotics,NSAIDS,statins,or probiotics within two months of study participation,and any patients who underwent chemotherapy or radiation treatments prior to surgery.We used orthogonal partial least-squares-discriminant analysis (OPLS-DA) for pattern recognition (dimension reduction) on 1H-NMR processed data (1H frequency of 400.13 MHz),to find metabolic differences among CR-Ad,carcinoma and HC fecal samples;and receiver operating characteristic (ROC) analysis to determine the diagnostic value of the fecal metabolic biomarkers.Results Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC (11 M,9 F,median age (52±13) years),25 with CR-Ad (14 M,11 F,median age (53±11) years) and 32 HCs (15 M,17 F,median age (53± 14) years).OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples,based on their metabolomic profiles.Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate (HC:23.0±6.0;CR-Ad:18.0±5.0;CRC:14.0±6.0;Z=-2.07,P=0.008),acetate (HC:45.0± 11.0;CR-Ad:31.0±11.0;CRC:24.0±8.0;Z=-2.32,P=0.011),propionate (HC:26.0 ± 7.0;CR-Ad:22.0 ± 6.0;CRC:19.0 ± 5.0;Z=-2.43,P=0.032),glucose (HC:37.0±7.0;CR-Ad:31.0±7.0;CRC:26.0±8.0;Z=-2.07,P=0.044) and glutamine (HC:4.5±2.0;CR-Ad:4.9 ± 1.0;CRC:5.4 ± 1.0;Z=2.21,P=0.044).However,relative signal intensities in HCs were significantly higher than in patients for lactate (HC:4.8± 1.0;CR-Ad:6.9±2.0;CRC:4.8± 1.0;Z=2.02,P=0.038),glutamate (HC:3.2±2.0;CR-Ad:4.9 ± 1.0;CRC:3.2± 2.0;Z=2.21,P=0.044) and succinate (HC:12.0±2.0;CR-Ad:15.0±3.0;CRC:12.0± 2.0;Z=2.25,P=0.011).Among the potential biomarkers,acetate at 1.92 ppm,and succinate at 2.41 ppm displayed relatively high area under ROC,with sensitivity and specificity both ＞90％,to distinguish early-stage CRC patients from HCs.Conclusion Fecal metabolic profiles distinguish of HCs from patients with CRC patients,even in the early stages (stage Ⅰ/Ⅱ),highlighting the potential of NMR-based fecal metabolomic fingerprinting as tools for early CRC diagnosis.