[Topography-guided transepithelial corneal collagen cross-linking by sequential ultraviolet A irradiation in different diameters for progressive keratoconus in adults].

Objective: To compare the efficacy and safety of a novel customized topography-guided transepithelial corneal collagen cross-linking (TG-CXL) procedure by sequential ultraviolet A irradiation in different diameters and conventional transepithelial corneal collagen cross-linking (TE-CXL) in adult patients with progressive keratoconus. Methods: A prospective cohort study was conducted. Adult patients diagnosed with progressive keratoconus in the Affiliated Xiamen Eye Center of Xiamen University were continuously recruited and randomly assigned to receive the TG-CXL or TE-CXL procedure from March 2020 to March 2021. Patients in the TE-CXL group were irradiated in the central 9-mm zone of the cornea (total energy, 7.2 J/cm2; irradiance, 45 mW/cm2), while patients in the TG-CXL group were first irradiated with the protocol used in the TE-CXL group, and further irradiated in the central 6-mm zone (total energy, 3.6 J/cm2; irradiance, 9 mW/cm2). The subjective symptom of pain and corneal fluorescein sodium staining were scored within postoperative 3 days. Slit lamp examination, measurements of uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), corneal topography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy, corneal endothelial cell count, and non-contact tonometry were performed before surgery and at 3, 6, and 12 months after surgery. Results: A total of 66 patients were enrolled (mean age, 23.0±3.3 years old), with 33 patients (33 eyes) in each group. No statistically significant differences were found in age, gender, and maximum keratometry (Kmax) between the two groups (P>0.05). On day 1 after surgery, the average pain score of the TG-CXL group (2.21±0.45) was significantly higher than that of the TE-CXL group (1.32±0.33) (P<0.05). The pain was rapidly alleviated in both groups on days 2 and 3. On days 1 and 2, the corneal fluorescein sodium staining scores in the TG-CXL group (4.15±0.83 and 2.21±0.60, respectively) were significantly higher than those in the TE-CXL group (1.76±0.56 and 0.85±0.51, respectively, P<0.001), while there was no significant difference between the two groups at day3 (P=0.184). The UCVA and BCVA of the TG-CXL group at 3, 6, and 12 months after surgery were significantly improved when compared with the baseline. At 3, 6, and 12 months, the BCVA (LogMAR) of the TG-CXL group (0.21±0.15, 0.22±0.16, and 0.22±0.16, respectively) were significantly improved when compared with those of the TE-CXL group(0.32±0.15, 0.34±0.15, and 0.36±0.16, respectively, P<0.01). However, there was no significant difference in UCVA between groups at any time point after surgery (P>0.05). The spherical and cylindrical power values of the TG-CXL group were improved when compared with the baseline (P<0.05). However, no significant difference in spherical power values was found between the two groups at any time point after surgery (P>0.05). Meanwhile, there were significant differences in cylindrical power values between the two groups at 6 and 12 months after surgery (P<0.05). The Kmax in the TG-CXL group was improved at all of the time points after surgery when compared with the baseline (P<0.001), while no significant difference in Kmax was found at any time point after surgery in the TE-CXL group when compared with the baseline (P>0.05). At 6 and 12 months after surgery, the Kmax values in the TG-CXL group were significantly lower than the TE-CXL group (P<0.05). No significant differences were found in flat keratomety, steep keratometry, the minimal thickness of the cornea, endothelial cell density, and intraocular pressure between the two groups at any time point after surgery (P>0.05). Within one month after surgery, optical coherence tomography revealed the increased density in the anterior stroma in both groups. In most patients in the TG-CXL group, a demarcation line was visible in the central and para-central corneal stroma, representing a clear and continuous, high-signal arc-shaped linear structure, which was deeper in the central cornea than the para-central cornea. In contrast, a demarcation line, fuzzy and focally discontinuous, was visible only in a few patients in the TE-CXL group, with an almost uniform depth in the central and the para-central cornea. Confocal microscopy demonstrated an apparent mesh-like cross-linked collagen structure in the superficial and intermediate corneal stroma at all time points after surgery in the TG-CXL group, with thickening stromal collagen fibers and an increased number of interconnections. In contrast, the mesh-like structure and number of interconnections in the superficial corneal stroma were significantly reduced at 12 months after surgery in the TE-CXL group, with no cross-linking structure in the intermediate corneal stroma at any time point after surgery. No serious complications such as corneal infection, sterile corneal ulcer, and persistent epithelial defect were observed in both groups during the follow-up of 12 months. Conclusions: The TG-CXL procedure by sequential irradiation in two different diameters with ultraviolet A light was effective and safe in the management of progressive keratoconus in adults, achieving significant refractive improvement. This might be a good technical alternative for refractive corneal cross-linking surgery.

[Artificial intelligence: a new journey in nephrology].

The rapid development of artificial intelligence (AI) technology, especially the progress in deep learning methods and computing power of hardware, has greatly promoted the application of AI in the field of biomedicine and nephrology. AI can predict the occurrence of acute kidney injury, identify chronic kidney disease, and assist in the analysis of kidney disease pathology, prognosis prediction and decision-making. The application of AI in the field of nephrology depends on the coordinated development of nephrology and artificial intelligence, and requires close interdisciplinary cooperation between multiple disciplines. This article describes the application and research progress of AI in nephrology and provides insights for future directions.

[Correlation between morphological characteristics of retinal microvessels and diabetic kidney disease in patients with type 2 diabetes mellitus based on a machine learning model].

Objective: To explore the correlation between the morphological characteristics of retinal microvessels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data and fundus photography of patients with T2DM treated in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively collected and analyzed. According to the presence of abnormal renal function, the patients were divided into DKD group and control group. The morphology and structure of fundus vessels were digitized by U-Net depth convolution neural network, and the correlation between fundus vascular morphology and DKD was analyzed by multivariate logistic regression. Results: A total of 648 patients with T2DM were enrolled, including 410 males and 238 females, and aged (53±10) years. There were 398 and 250 cases in control and DKD groups, respectively. Meanwhile, 1 296 fundus images were collected. Compared with control group, the male ratio (68.4% vs 60.1%, P=0.032), age [(54±9) vs (52±10) years, P=0.005], blood pressure [(136.8±17.3) vs (130.3±15.4) mmHg（1 mmHg=0.133 kPa）, P<0.001], total cholesterol [(4.5±1.4) vs (4.2±1.0) mmol/L, P=0.009], triglyceride [M (Q1, Q3)][1.7 (1.2, 3.0) vs 1.4 (1.0, 2.3) mmol/L, P<0.001] and Cystatin C [(0.9 (0.8, 1.0) vs 0.8 (0.7, 0.9) mg/L, P<0.001] were higher in the DKD group, while high-density lipoprotein [(1.0±0.3) vs (1.1±0.3) mmol/L, P=0.001] was lower in the DKD group. Multivariate logistic regression analysis showed that the risk of DKD in the third quartile (right eye: OR=1.825, 95%CI: 1.204-2.768, P=0.005) and fourth quartile (left eye: OR=1.929, 95%CI: 1.218-3.055, P=0.005) was higher than that in the lowest quartile of vascular curvature after adjusting for age and gender. The increase of average diameter of retinal vein was associated with the risk of DKD (left eye: OR=1.044, 95%CI: 1.013-1.075, P=0.005). The decrease of vascular fractal dimension (fourth quartile of left eye: OR=0.444, 95%CI: 0.199-0.987, P=0.046) and retinal vascular density (the second and fourth quartile of the right eye: OR=0.639, 95%CI: 0.409-0.998, P=0.049; OR=0.534, 95%CI: 0.331-0.864, P=0.010) were related to the risk of DKD. Conclusions: The abnormal morphological characteristics of retinal microvessels are related to the occurrence of DKD. The increase of retinal vein diameter and the decrease of retinal vessel density correlate with the occurrence of DKD.

[Prevalence and risk factors of chronic kidney disease in diabetic population aged over 40 years in Henan province].

Objective: To investigate the prevalence and risk factors of chronic kidney disease (CKD) in diabetic patients aged over 40 years in Henan province. Methods: A cross-sectional study was conducted. Diabetic patients aged over 40 years were recruited from four cities including Xuchang, Zhumadian, Luoyang and Zhengzhou in Henan Province between June 2015 and July 2019. Multivariate logistic regression analysis was employed to analyze the risk factors for CKD. Results: A total of 3 067 diabetic patients were included in this study, including 1 238 males and 1 829 females. The mean age of all participants was (60.9±9.7) years and 85.8% (2 633/3 067) of them were living in rural areas. There were 1 155 participants who had CKD, and the overall prevalence of CKD was 37.7% (95%CI: 35.9%-39.4%). Compared with those without CKD, participants with CKD had older age [(61.4±10.3) vs (60.6±9.3) years], higher proportion of male patients (43.2% vs 38.7%), urban residents (19.4% vs 11.0%) and habitual drinkers (15.8% vs 12.7%), higher body mass index [(25.8±3.7) vs (25.4±3.6) kg/m2), higher proportion of having hypertension (57.0% vs 37.2%), hyperuricemia (10.7% vs 7.1%) and dyslipidemia (46.5% vs 42.7%) (all P<0.05). The prevalence of estimated glomerular filtration rate (eGFR) less than 60 ml·min-1·(1.73 m2)-1 and albuminuria was 4.9% (149/3 067) and 35.6% (1 092/3 067), respectively. Compared with rural participants [35.4% (95%CI: 34.4%-36.4%)], urban participants [51.6% (95%CI: 50.0%-53.2%)] had higher prevalence of CKD (P<0.001). Multivariate logistic regression analysis showed that habitual drinker (OR=1.27, 95%CI: 1.00-1.61, P=0.046), moderate physical activities (OR=1.23, 95%CI: 1.01-1.51, P=0.039), having hypertension (OR=2.27, 95%CI: 1.95-2.64, P<0.001), dyslipidemia (OR=1.21, 95%CI: 1.04-1.40, P=0.012) and hyperuricemia (OR=1.56, 95%CI: 1.21-2.02, P=0.001) were independent risk factors for CKD. Conclusions: The prevalence of CKD is high in diabetic patients who aged over 40 years in Henan province. The associated factors for developing CKD include habitual drinking, heavier physical activities and having chronic diseases. Targeted prevention and intervention for associated factors would be beneficial for controlling CKD in middle and old aged diabetic patients.

[Correlation between polycyclic aromatic hydrocarbons component phenanthrene and clinical indicators in patients on peritoneal dialysis].

Objective: To explore the correlation between polycyclic aromatic hydrocarbons (PAHs) component phenanthrene and clinical indicators in patients on continuous ambulatory peritoneal dialysis (CAPD). Methods: A total of 22 patients who underwent peritoneal dialysis catheterization and regular dialysis in the First Affiliated Hospital of Zhengzhou University from June to August 2018 were selected. Meanwhile, 18 healthy adults who underwent physical examination were also selected as the control group. Fasting blood samples were taken to detect the concentration of PAHs components for comparison, and the correlation between PAHs components and clinical indicators was further analyzed. Results: There were 22 cases in CAPD group (13 males and 9 females), and aged (45±13) years, while there were 18 cases in control group (6 males and 12 females), and aged (41±13) years. The concentration of blood phenanthrene (PHE) was the highest in CAPD group [0.449 (0.254, 0.581) mg/L], and it was only lower than acenaphthene in the control group [0.081 (0.050, 0.444) mg/L], with a statistically significant difference between the two groups (P=0.008). The analysis of PHE and clinical indicators showed that the concentration of PHE in CAPD patients was negatively correlated with weekly urea clearance index (Kt/V), weekly creatinine clearance (Ccr) and leukocyte level, but positively correlated with triglyceride level (r=-0.743, -0.749, -0.655 and 0.610, respectively, all P<0.05). Simple linear regression analysis demonstrated that for every 0.1 mg/L increase in PHE concentration, weekly Kt/V, weekly Ccr and white blood cell count decreased by 0.226, 3.050 L/1.73 m2 and 0.512×109/L, respectively, but triglyceride level increased by 0.152 mmol/L (all P<0.05). Multiple linear regression analysis revealed that the blood PHE concentration of CAPD patients was negatively correlated with weekly Kt/V and Ccr levels (t=-2.402 and -2.368, respectively, both P<0.05). All CAPD patients were followed up for 3 years, during which 8 patients (36.4%) withdrew from peritoneal dialysis due to technical failure, and the baseline PHE concentration was higher than that of patients who did not quit peritoneal dialysis [0.572 (0.416, 0.662) vs 0.268 (0.120, 0.475) mg/L, P=0.003]. Eight patients (36.4%) had cardiovascular events, and the baseline blood PHE concentration was higher than that of patients without cardiovascular events [0.542 (0.389, 0.741) vs 0.373 (0.157, 0.545) mg/L, P=0.045]. Conclusion: PHE correlates with clinical indicators of CAPD patients, including Kt/v, Ccr, leukocyte and triglyceride.

[Short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease].

Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m2 (HR=5.04, 95%CI: 1.50-16.91, P=0.009) and biological remission at 6 weeks of treatment (HR=15.22, 95%CI: 3.16-73.38, P=0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

A novel risk prediction model of pyroptosis-related genes for the prognosis and immunotherapy response of endometrial cancer.

OBJECTIVE: This study aims to develop a risk prediction model of pyroptosis-related genes based on its impact on immunotherapy sensitivity of uterine corpus endometrial carcinoma (UCEC), one of the most common and threatening gynecological malignancies. PATIENTS AND METHODS: Through multiple bioinformatics analysis, we obtained raw counts of RNA-sequencing data and corresponding clinical information related to UCEC from The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) to investigate the potential mechanisms of differentially expressed pyroptosis-related genes (DEPRGs), including the correlation between DEPRGs and prognosis, tumor immune microenvironment and the immunotherapy sensitivity of UCEC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis were used to figure out the functional differences. Furthermore, a mRNA-miRNA-lncRNA network was constructed to identify potential impact of pyroptosis on tumor progression. RESULTS: In this study, we achieved six DEPRGs (CASP3, GPX4, GSDMD, NOD2, PYCARD and TIRAP) and constructed a 6-gene signature which classified UCEC patients in the TCGA cohort into a low-risk group or a high-risk group. Patients in the low-risk group showed significantly longer survival time (p=0.000373). The risk score was also confirmed as an independent prognostic factor combining with the clinical characteristics. GO and KEGG functional analysis revealed the possible molecular mechanisms by which six DEPRGs influence anti-tumor immunity in UCEC patients. In addition, we found that two DEPRGs (GPX4, TIRAP) were not only significantly associated with tumor mutational burden (TMB) or microsatellite Instability (MSI), but also involved in regulating the number and function of CD8+ cells. CONCLUSIONS: Upon comprehensive bioinformatics analysis, it was concluded that pyroptosis-related genes (PRGs) could predict the prognosis of EC patients and be affected in modulating the anti-tumor immune responses for patients with EC.

[Prevention and treatment of hyperkalemia in chronic kidney disease].

Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease, and can be life-threatening in severe cases. It is an emergency that every clinician should recognize and master. This paper briefly describes the risk of hyperkalemia in order to pay more attention to hyperkalemia, summarizes the strategies for the treatment of hyperkalemia and reviews different treatment methods, so as to provide ideas for the treatment of hyperkalemia and improve the prognosis of patients.

[Prevalence and related factors of hyperkalemia in patients with diabetic kidney disease].

Objective: To explore the prevalence and related factors of hyperkalemia in patients with diabetic kidney disease (DKD). Methods: DKD patients from the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were selected, and the clinical data of the patients were retrospectively collected. The prevalence of hyperkalemia in DKD patients and the prevalence of hyperkalemia in patients with different age, gender and different stages of chronic kidney disease (CKD) were studied, and the related factors of hyperkalemia were further explored. Results: A total of 1 721 patients with DKD were included, with 1 117 males (64.9%) [mean age: (56±12) years] and 604 females (35.1%) [mean age: (59±12) years]. The blood potassium level of the study population was (4.93±0.77) mmol/L, in which the serum potassium level of male and female was (4.92±0.77) mmol/L and (4.93±0.76) mmol/L, respectively, and the difference was not statistically significant (P=0.752). Further grouping by CKD stage, the serum potassium levels of CKD stage 1-5 patients were (4.58±0.52), (4.65±0.47), (4.86±0.59), (5.21±0.79) and (5.61±0.88) mmol/L, respectively, and the difference was statistically significant (F=170.701, P<0.001). The prevalence of hyperkalemia was 37.0% (636/1 721). The prevalence of mild, moderate and severe hyperkalemia was 17.4%, 10.5% and 9.1%, respectively. There was no significant difference in the prevalence of hyperkalemia between men and women (36.8% vs 37.3%, χ²=0.035, P=0.851). The prevalence of hyperkalemia in CKD stage 1-5 patients was 16.3%, 21.2%, 37.6%, 55.2%, 72.5%, respectively, which increased with the severity of CKD (χ²=365.721, P<0.001). Multivariate logistic regression showed that estimated glomerular filtration rate (OR=0.975, 95%CI: 0.972-0.979), diastolic blood pressure (OR=0.985, 95%CI: 0.975-0.994) and serum sodium concentration (OR=0.972, 95%CI: 0.945-1.000) were the influencing factors of hyperkalemia in DKD patients. Conclusions: The prevalence of hyperkalemia in DKD patients was 37.0%. Glomerular filtration rate, diastolic blood pressure and serum sodium concentration were the influencing factors. The serum potassium level and the prevalence of hyperkalemia increased with the deterioration of renal function.

[Analysis of risk factors for hyperkalemia in hemodialysis patients and establishment and verification of risk assessment model of hyperkalemia].

Objective: To explore risk factors for hyperkalemia in hemodialysis (HD) patients, and establish and verify a risk assessment model of hyperkalemia in HD patients. Methods: The clinical data of HD patients who were admitted to the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University between April 2020 and January 2021 were retrospectively collected and divided into training dataset and validation dataset by using the conversion-random number generator. In the training dataset, multivariate logistic regression analysis was used to screen the risk factors for hyperkalemia in HD patients and the factors were scored to establish the risk assessment model. The validation dataset was substituted into the model and the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to verify the effectiveness of the risk prediction model in predicting hyperkalemia. Results: A total of 502 HD patients were enrolled and further divided into training dataset (n=372) and validation dataset (n=130). There were 268 males and 234 females, with a mean age of (54±13) years. Multivariate logistic regression analysis showed that metabolic acidosis, high potassium diet, history of hyperkalemia, the change of electrocardiogram (ECG), disfunction of vascular access and time interval from last dialysis were risk factors for causing hyperkalemia in patients undergoing HD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.799. Using 5 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events was 61.4% and 86.3%, respectively. Conclusion: The current study preliminarily established a risk assessment model for hyperkalemia in HD patients, which can help clinicians manage the potassium level of HD patients.

[Early infantile epileptic encephalopathy caused by PACS2 gene variation: three cases report and literature review].

Objective: To explore the clinical features of three early-onset infantile epileptic encephalopathy (EIEE) patients with variations in phosphofurin acidic cluster sorting protein 2 (PACS2) gene and to review related literature. Methods: The clinical data and genetic features of three early infantile epileptic encephalopathy 66 (EIEE66) patients with a PACS2 gene variant diagnosed by the Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2020 were retrospectively analyzed. A literature search with "PACS2 gene" "PACS2" "epileptic encephalopathy, early infantile, 66" and"early infantile epileptic encephalopathy 66" as key words was conducted at PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (up to July 2020). Case reports of patients with PACS2 gene variants and related clinical data were chosen and reviewed. Results: Case 1, a girl aged 2 years and 2 months was hospitalized because of repetitive seizures within more than two years and 6 convulsions within 2 days due to fever. The seizures occurred at the age of 7 days, characterized by focal seizures and generalized tonic-clonic seizures. Sometimes, the frequency of seizures increased with high fever. Regular treatment had not been implemented in the early stage, later seizures were controlled by valproic acid treatment. Case 2, a female 5 months of age, was admitted due to recurrent convulsions in nearly five months. Focal seizures occured at the age of 5 days. And the brain magnetic resonance imaging (MRI) confirmed abnormal cerebellar hemispheres and cerebellar vermis, as well as cerebellar dysplasia. Several antiepileptic drugs and ketogenic diet were ineffective in the early months, and later seizures were controlled with the treatment with levetiracetam and valproic acid. Case 3, a five-month-old girl, was admitted because of recurrent convulsions for nearly five months. At the age of 3 days, she had tonic seizures, and showed good response to levetiracetam and valproic acid. All the three cases were accompanied by development delay and dysmorphic facial appearance, and got seizure-free with the treatment with valproic acid. All copy-number variant analysis and trio whole exome sequencing revealed a recurrent heterozygous missense variant (c.625G>A) in PACS2 gene. No related reports were found in Chinese journals, while 4 reports were found in English literature, describing 17 patients in total. With these 3 patients included, 20 cases had only two missense PACS2 gene variants, in whom 19 cases carried the variant c. 625G>A (p.Glu209Lys) and 1 case carried the variant c. 631G>A (p.Glu211Lys). Epilepsy was the first reported symptom in all patients, and 17 cases had seizures during the first week of life. Out of the various seizure types observed, focal seizures were the predominant types (13 cases), whereas tonic, clonic, tonic-clonic seizures and non-motor seizures (such as facial flushing) were also reported. Almost all patients showed facial dysmorphism and developmental delay to different degrees. Total of 16 patients had abnormal brain MRI recordings, and 13 cases had cerebellar hypoplasia. More specifically, 7 cases showed inferior vermian hypoplasia, and 3 cases showed hypothalamic fusion anomaly. The treatment was mainly aimed to control the symptoms. And the recommended effective treatment for epilepsy has not been reported yet. Conclusions: PACS2-related early infantile epileptic encephalopathy is an autosomal dominant disease, characterized by seizure onset within the first week of life in most cases, dysmorphic facial appearance, and various degrees of developmental retardation. Treatment with valproic acid showed good effect.

[The correlation between polycyclic aromatic hydrocarbons and idiopathic membranous nephropathy].

Objective: To explore the relationship between polycyclic aromatic hydrocarbons (PAHs), the major component of atmospheric pollutant particulate matter 2.5 (PM2.5) and idiopathic membranous nephropathy (IMN) and its possible mechanisms. Methods: Thirty-five (24 males and 11 females) patients with IMN confirmed by renal biopsy pathology in the First Affiliated Hospital of Zhengzhou University from June to September 2020 were selected as the research group, with an age of (47.3±12.9) years. Meanwhile, patients with secondary membranous nephropathy (SMN, n=10) and minimal-change disease (MCD, n=10) were selected as control group. Blood samples were collected to detect PAHs and heme oxygenase-1 (HO-1), and the relationship of PAHs with clinical indicators and oxidative stress indicator HO-1 was analyzed. Results: Compared with SMN and MCD groups [(2.6±1.7) mg/L and (2.8±1.0) mg/L], the concentration of PAHs in IMN group [(4.1±1.9) mg/L] increased (both P<0.05). The concentration of PAHs was positively correlated with the levels of ß2 microglobulin, total cholesterol and 24-hour urine total protein (r=0.509, 0.336, and 0.653, respectively, all P<0.05), but was negatively correlated with the levels of total protein and albumin (r=-0.499,-0.530, respectively, both P<0.05). Additionally, the concentration of PAHs was negatively correlated with the level of HO-1 (r=-0.358, P=0.017). Linear regression analysis showed that the concentration of HO-1 decreased by 1.737 µg/L when the concentration of PAHs increased by 1 mg/L (P=0.035). Conclusion: PAHs have a high level in IMN patients, and may be involved in the occurrence and development of IMN through oxidative stress.

[Treatment of diabetic kidney disease: research development, current hotspots and future directions].

Diabetic kidney disease (DKD) has emerged as the primary cause of chronic kidney disease, posing a huge economic and social burden. Therefore, it is urgent to strengthen the prevention and treatment of DKD. However, due to the complex pathogenesis of DKD and the lack of specific and effective intervention targets, there is currently no breakthrough in treatment, thereby causing the continuous increase of end-stage DKD. This review examines several key nodes in the progress of DKD treatment, in order to standardize the clinical treatment, promote the research progress, and improve the prognosis of DKD.

[Effects and mechanisms of Xuezhikang on preventing contrast-induced acute kidney injury in diabetic rats].

Objective: To explore the effects and mechanisms of Xuezhikang on preventing contrast-induced nephropathy (CIN) in diabetic rats. Methods: Streptozotocin (65 mg/kg) was injected intraperitoneally to establish a diabetes model in 7-week-old male Sprague-Dawley (SD) rats. After 4 weeks of modeling, 24 diabetic rats were randomly divided into 4 groups: sham group, CIN group, CIN+vehicle (Veh) group and Xuezhikang group. All animals were sacrificed at 24 hours after administration of contrast. Blood and kidney tissues were collected to detect biochemical, inflammation-related, oxidative stress-related and pathological indicators. Results: After administration of contrast agent, the renal function-related indicators were decreased in Xuezhikang group compared with CIN+Veh group [serum creatinine (SCr): (59.3±3.3) µmol/L vs (73.2±4.1) µmol/L; blood urea nitrogen (BUN): (13.8±0.5) mmol/L vs (16.3±0.6) mmol/L; serum neutrophil gelatinase-associated lipocalin (sNGAL): (41.4±2.0) ng/ml vs (54.9±4.4) ng/ml; urinary kidney injury moleculer-1 (uKIM-1): (11.1±0.5) ng/ml vs (16.6±0.5) ng/ml] (all P<0.05). Histological analysis showed that the severity of renal tubule dilatation, brush border loss and renal tubular cell necrosis in Xuezhikang group was better than that of CIN+Veh group. Additionally, the oxidative stress-related indicators of Xuezhikang group improved compared with those of CIN+Veh group [malondialdehyde (MDA): (12.1±0.7) nmol/mg vs (15.5±0.8) nmol/mg, superoxide dismutase (SOD): (35.0±2.2) U/mg vs (23.7±3.4) U/mg, renal nitrite: (1.7±0.1) nmol/mg vs (1.2±0.1) nmol/mg, all P<0.05]. Meanwhile, Xuezhikang pretreatment downregulated the mRNA and protein expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (both P<0.05). Conclusion: The current study suggests that Xuezhikang protects against CIN in diabetic rats by inhibiting oxidative stress and inflammation.

[Development of a hyperkalemia risk assessment model for patients with chronic kidney disease].

Objective: To investigate risk factors for hyperkalemia among chronic kidney disease (CKD) patients and establish a risk assessment model for predicting hyperkalemia events. Methods: Clinical data of CKD patients (stage 3 to 5) hospitalized between May 2017 and June 2020 from 14 hospitals were retrospectively collected and divided into training dataset and validation dataset through balanced random sampling. Multivariate logistic regression analysis was used to analyze risk factors for hyperkalemia in CKD patients and the factors were scored. Receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Meanwhile, the cut-off value with the best sensitivity and specificity were used to verify the accuracy of the model in validation dataset. Results: A total of 847 CKD patients were enrolled and further divided into training dataset (n=675) and validation dataset (n=172). There were 555 males and 292 females, with a mean age of (57.2±15.6) years. Multivariate logistic regression analysis showed that age, CKD stage, history of heart failure, history of serum potassium ≥5.0 mmol/L, diabetes, metabolic acidosis, and use of medications that increase serum potassium levels were risk factors for causing hyperkalemia in patients with CKD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.809. Using 4 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events reached 87.1% and 57.0%, respectively. Conclusion: The model established in the current study can be used for predicting hyperkalemia events in clinical practices, which offers a new way to optimize serum potassium management in patients with CKD.

RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6.

OBJECTIVE: RBBP6 is identified to be a cancer-associated gene by bioinformatics analysis. This study aims to explore the role of RBBP6 in regulating proliferation and metastasis in ovarian cancer, thus providing theoretical references for ovarian cancer treatment. PATIENTS AND METHODS: Differential expressions of RBBP6 in ovarian cancer and normal ones were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between RBBP6 and prognosis in ovarian cancer patients was analyzed. The interaction between RBBP6 and PIK3R6 was detected by bioinformatics analysis and Dual-Luciferase reporter assay. Moreover, regulatory effects of RBBP6 and PIK3R6 on proliferative and migratory potentials in A2780 and CAOV3 cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Finally, tumorigenicity assay was conducted in nude mice to illustrate the in vivo regulations of PBBP6 and PIK3R6 on ovarian cancer growth. RESULTS: RBBP6 was upregulated in ovarian cancer tissues than normal ones. RBBP6 was irrelevant to age, tumor size and tumor node metastasis (TNM) staging in ovarian cancer patients, but correlated to lymphatic metastasis and distant metastasis. RBBP6 was abundantly expressed in ovarian cancer cells, and among the tested cell lines, CAOV3 and A2780 expressed the highest level of RBBP6. Knockdown of RBBP6 attenuated in vitro proliferative and migratory potentials in CAOV3 and A2780 cells. PIK3R6 was the target gene binding RBBP6, which was positively regulated by RBBP6. Overexpression of PIK3R6 could abolish the inhibited proliferative and migratory potentials in ovarian cancer cells with RBBP6 knockdown. In addition, the knockdown of RBBP6 slowed the in vivo growth of ovarian cancer in nude mice, and the alleviated cancer progression was reversed by overexpression of PIK3R6. CONCLUSIONS: RBBP6 is highly expressed in ovarian cancer cases, which stimulates proliferative and migratory potentials by targeting PIK3R6. RBBP6 may be a novel therapeutic target for ovarian cancer.

[Investigation on the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children].

Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

[Changes of urinary monocyte chemotactic protein 1 and epidermal growth factor and their correlations with clinicopathology in idiopathic membranous nephropathy patients].

Objective: To explore the changes and clinical value of urinary monocyte chemotactic protein 1 (MCP-1), epidermal growth factor (EGF) and their ratio in patients with idiopathic membranous nephropathy (IMN). Methods: A total of 67 IMN patients were enrolled according to kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2018. The patients included 28 males and 39 females, with an average age of (47.6±14.2) years. Eighteen age-and sex-matched healthy controls were also enrolled. Clinical and pathological data, blood and urine samples of all subjects were collected. Urinary MCP-1 and EGF level were detected by enzyme-linked immunosorbent assay (ELISA). And then the levels of urinary MCP-1, EGF and the ratio of EGF/MCP-1 and their correlations with clinicopathology were analyzed. Results: There was no statistical difference of the urine EGF levels between the two groups [8.3(6.0,12.6) vs 8.4(6.5,10.2) ng/mg Cr, P=0.575]. The urine MCP-1 levels of IMN patients were 0.37 (0.21, 0.69) ng/mg Cr, which was statistical significantly higher than those of the control group [0.09 (0.02, 0.19) ng/mg Cr] (P<0.001), while the EGF/MCP-1 ratio was lower than that of the control group [22.2(15.1,36.6) vs 87.6(71.2,132.7), P<0.001]. Urine MCP-1 was negatively correlated with eGFR (r=-0.303, P=0.012), but positively correlated with the urinary ratio of albumin to creatinin (r=0.368, P=0.002). EGF was positively correlated with eGFR (r=0.722, P<0.001), but negatively correlated with the severity of interstitial fibrosis and renal tubular atrophy (IFTA) (r=-0.312, P=0.011). EGF/MCP-1 ratio was positively correlated with eGFR (r=0.693, P<0.001), but negatively correlated with the severity of the urinary ratio of albumin to creatinin and IFTA (r=-0.261, P=0.028 and r=-0.684, P<0.001, respectively). Further multivariate logistic regression analysis showed that EGF/MCP-1 was a protective factor for moderate-to-severe IFTA (OR=0.891, 95%CI: 0.844-0.949, P=0.008). Conclusion: Patients with IMN have elevated urine MCP-1 level and decreased EGF/MCP-1 ratio, which correlate with clinical indicators. In particular, EGF/MCP-1 ratio is independently related to moderate-severe IFTA, and may be a potential clinical biomarker for diagnosis of IMN.