AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P＜0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P＜0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P＜0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P＜0.01),with increased levels in the ESAX-offspr group(P＜0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P＜0.01),while levels in the ESAX-offspr group were reduced(P＜0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.

AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P＜0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P＜0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P＜0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P＜0.01),with increased levels in the ESAX-offspr group(P＜0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P＜0.01),while levels in the ESAX-offspr group were reduced(P＜0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.

AIM:To explore the mechanisms behind the inhibition of lymphangiogenesis in pregnant rats with obstructive nephropathy and assess the protective effects on kidney function.METHODS:Forty nulliparous female Wi-star rats were randomly assigned to four groups:sham operation,sham operation+pregnancy,model,and Esaxerenone groups,with 10 rats in each group.Renal injury was induced in the model and Esaxerenone groups via unilateral ureteral obstruction(UUO).The other two groups underwent ureteral dissociation without ligation.Nine weeks post-UUO,female rats in the sham operation+pregnancy,model,and Esaxerenone groups were mated with male rats(2:1 ratio)to establish a rat model of obstructive nephropathy during pregnancy.Starting the day after UUO,rats in the Esaxerenone group re-ceived Esaxerenone at 1 mg·kg-1·d-1.On the 18th day of pregnancy,24-hour urine was collected using metabolic cages.The following day,the rats were sacrificed,serum samples collected,and the contralateral kidney removed.Blood urea ni-trogen(BUN)was measured using standard biochemical methods,and endogenous creatinine clearance rate(Ccr)was calculated.Kidney tissue pathology was assessed using HE,Masson,and Sirius red staining.Serum aldosterone levels were determined via ELISA.Immunohistochemistry,real-time PCR,and Western blot were employed to assess mineralo-corticoid receptor(MR)activation,lymphangiogenesis,signaling pathways,and fibrosis-related markers.RESULTS:Renal function tests revealed increased BUN levels and decreased Ccr in the model group(P<0.01).Pathological exami-nation showed dilated renal tubules,significant collagen deposition,and inflammatory cell infiltration in the model group.ELISA results indicated a significant increase in serum aldosterone levels in the model group(P<0.01).Immunohisto-chemistry showed enhanced nuclear translocation of MR in the kidneys of the model group post-activation.Western blot and real-time PCR demonstrated a marked increase in neutrophil gelatinase-associated lipocalin(NGAL)expression in the model group(P<0.01).Additionally,the expression of vascular endothelial growth factor C(VEGF-C)and its receptor VEGFR3 was significantly elevated in the renal tubulointerstitium of the model group,as shown by both immunohistochem-istry and real-time PCR(P<0.01).The PI3K/Akt signaling pathway was activated in the model group,with significantly increased phosphorylation levels observed primarily in renal tubular epithelial and interstitial cells(P<0.01).Collagen type III(Col III)expression,primarily in the renal tubulointerstitium,was also significantly upregulated in the model group,consistent with real-time PCR results(P<0.01).Esaxerenone treatment improved renal function,reduced patho-logical damage,inhibited aldosterone secretion,and downregulated the expression of MR,NGAL,VEGF-C,VEGFR3,phosphorylated PI3K,phosphorylated Akt,and Col III(P<0.01).CONCLUSION:Esaxerenone mitigates aldosterone-induced MR activation,modulates the PI3K/Akt signaling pathway,reduces lymphangiogenesis in the contralateral kidney of pregnant rats with obstructive nephropathy,decreases collagen deposition,and delays the progression of renal intersti-tial fibrosis.

Objective:To evaluate the expression level of hsa-miR-422a in hypertrophic scars and to identify the target genes of hsa-miR-422a along with their biological functions using bioinformatics approaches.Methods:From June 2020 to December 2020, tissue samples of 3 hypertrophic scar and 3 normal skin were collected from patients (3 males, 3 females, aged 20-42 years) in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine. Primary fibroblasts were isolated and cultured. Real-time quantitative PCR was performed to quantify the expression of hsa-miR-422a. To construct a ceRNA network, starbase and Target Scandata bases were utilized to predict genes as well as long noncoding RNAs (lncRNAs) that may sponge hsa-miR-422a. GO and KEGG pathway enrichment analyses were conducted on the target genes of hsa-miR-422a; protein-protein interaction (PPI) networks were constructed to identify the hub genes whose functions were predicted by functional enrichment analyses. The expression of hub genes was validated through real-time quantitative PCR in hypertrophic scars.Results:The expression of hsa-miR-422a was significantly lower in the hypertrophic scar tissue samples and fibroblasts compared to that in the normal skin ( P<0.05). 133 target genes as well as 1033 lncRNAs were predicted by starBase and TargetScandata bases and used to construct an hsa-miR-422a-centered ceRNA network. PPI networks of the target genes revealed 10 hub genes, including MAPK1, GRB2, and IGF1R, which were discovered to be related to protein serine/threonine/tyrosine kinase activity, ubiquitin protein ligase binding, fibroblast growth factor receptor signaling pathway, muscle cell proliferation, and many others; besides, they may be involved in FoxO, mTOR, Toll-like receptor, Ras, MAPK, PI3K-Akt signaling pathways and signaling pathways regulating pluripotency of stem cells. Three hub genes (MAPK1, GRB2, and IGF1R) were significantly upregulated in hypertrophic scars ( P<0.05). Conclusions:hsa-miR-422a is significantly downregulated in the hypertrophic scars and may target hub genes such as MAPK1 in ceRNA networks, ultimately modulating hypertrophic scar formation.

OBJECTIVES: To evaluate the feasibility and safety of bipolar-plasmakinetic transurethral enucleation and resection of the prostate (B-TUERP) in day surgery. METHODS: From January 2021 to August 2022, 34 patients with benign prostatic hyperplasia (BPH) underwent B-TUERP in day surgery in the First Affiliated Hospital of Anhui Medical University. Patients completed the screening and anesthesia evaluation before admission and received the standard surgery which implements "anatomical enucleation of the prostate" and "absolute bleeding control" on the same day of admission, and by the same doctor. Bladder irrigation was stopped, catheter was removed and the discharge evaluation was performed on the first day after operation. The baseline data, perioperative conditions, time of recovery, treatment outcomes, hospitalization costs, and postoperative complications were analyzed. RESULTS: All operations were successfully conducted. The average age of the patients was (62.2±7.8) years, average prostate volume was (50.2±29.3) mL. The average operation time was (36.5±19.1) min, the average hemoglobin and blood sodium were decreased by (16.2±7.1) g/L and (2.2±2.0) mmol/L, respectively. The average postoperative length of hospital stay, and total length of hospital stay were (17.7±2.2) and (20.8±2.1) h, respectively, and the average hospitalization cost was (13 558±2320) CNY. All patients were discharged on the day after surgery except for one patient who was transferred to a general ward. Three patients received indwelling catheterization after catheter removal. The 3-month follow-up results showed a substantial improvement in the International Prostate Symptom Score, quality of life score and maximum urinary flow rate (all P<0.01). Three patients experienced temporary urinary incontinence, 1 patient experienced urinary tract infection, 4 patients were diagnosed with urethral stricture and 2 patients experienced bladder neck contracture. No complications above Clavien grade Ⅱ occurred. CONCLUSIONS The preliminary results showed that B-TUERP ambulatory surgery is a safe, feasible, economical and effective treatment for appropriately selected patients with BPH.
Male ; Humans ; Middle Aged ; Aged ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Ambulatory Surgical Procedures ; Quality of Life ; Feasibility Studies ; Retrospective Studies ; Treatment Outcome

Spinal muscular atrophy, lower extremity-predominant, 2A (SMALED2A) is a form of spinal muscular atrophy, which predominantly affects muscles of the lower extremity, characterized by early childhood onset of muscle weakness and atrophy. This disorder is caused by mutation in the BICD2 gene. This paper reports a case of SMALED2A with recurrent skin ulceration of both feet. Whole exome sequencing of this case revealed a chr9∶95527083_A>AGCC insertion mutation in the 5’UTR of BICD2 gene.

To detect the expression of galectin-13 in allergic diseases and provide a new way for the diagnosis and treatment of allergic diseases. A retrospective analysis method was used to screen 216 patients with allergic diseases with house dust mites or aspergillus as allergens who visited the Department of Allergy and Department of Respiratory of Tongji Hospital attached Tongji Medical College, Huazhong University of Science and Technology from March 2018 to May 2021. These allergic diseases included allergic asthma, allergic bronchopulmonary aspergillosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic urticaria. 25 subjects without underlying diseases were selected as healthy controls. The galectin-13 content in serum in each group were detected, and the Pearson correlation was used to determine the correlation between the galectin-13 content in serum in each group and blood eosinophil count, blood specific IgE, the score scale of allergic disease. The expression of Galectin-13 was increased in allergic asthma group (71.44±39.44) pg/ml, allergic bronchopulmonary aspergillosis group (100.10±47.62) pg/ml, allergic rhinitis group (54.11±24.81) pg/ml and dermatitis group (44.12±19.51) pg/ml. The expression of galectin-13 was not significantly increased in allergic urticaria group (32.75±10.29) pg/ml and the allergic conjunctivitis group (30.55±9.87) pg/ml. The galectin-13 content in serum, was positively correlated with blood eosinophil count( r s=0.54, P<0.001) and house dust mite specific IgE ( r s=0.51, P<0.001) in allergic asthma group, and was positively correlated with blood eosinophil count( r s=0.63, P=0.025) and aspergillus fumigatus specific IgE ( r s=0.58, P=0.046) in allergic bronchopulmonary aspergillosis group. It was positively correlated with blood eosinophil count ( r s=0.52, P=0.000 2) and house dust mite specific IgE ( r s=0.41, P=0.005) in allergic rhinitis group. In allergic conjunctivitis group, the expression of galectin-13 was positively correlated with conjunctivitis symptom score ( r s=0.47, P=0.048). In atopic dermatitis group, the expression of galectin-13 was positively correlated with blood eosinophil count ( r s=0.58, P<0.001) and house dust mite specificity IgE ( r s=0.47, P=0.002). In allergic urticaria group, the expression of galectin-13 was not significantly correlated with blood eosinophil count or house dust mite specific IgE. Galectin-13 may be related to the occurrence and progress of allergic diseases and may be involved in the occurrence of eosinophilic inflammation.

Objective:To analyze the plasma metabolomic characteristics of elderly patients with acute myocardial infarction and identify potential metabolic makers.Methods:Thirty elderly patients with acute myocardial infarction at the Second Affiliated Hospital of Soochow University were enrolled into the myocardial infarction group and thirty elderly people recruited at the physical examination center and meeting the inclusion criteria served as the control group.Plasma metabolites were measured by ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry.Information about metabolites was searched and sorted via the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Principal component analysis and orthogonal partial least square-discriminant analysis were carried out to compare overall trends and the Mann-Whitney U test was used for preliminary screening of differential metabolites in the two groups.Then the Mann-Whitney U test and a model of mutual information with random forests were used to analyze the importance of differential metabolites.A tandem liquid chromatography-mass spectrometry-based approach was subsequently performed for targeted detection of the content of differential metabolites in the two groups, and the t-test was used for comparison between the two groups. Results:There were no significant differences in the prevalence of hypertension, hyperlipidemia and diabetes mellitus between the two groups( P>0.05), while the plasma troponin T level in the myocardial infarction group was significantly higher than that in the control group, (2.16±0.36)μg/L vs.(0.26±0.03)μg/L( t=5.17, P<0.05). A clear difference in the overall trend was presented on the scatter plot of PCA and OPLS-DA, and a total of 32 differential metabolites met the preliminary screening criteria.Further analysis showed that pyrocatechol and 4 small peptides were closely correlated with grouping and was strongly predictive of group designation.Targeted quantification revealed the pyrocatechol concentration was(310.3±40.0)ng/L in the myocardial infarction group and(2 607.0±758.1)ng/L in the control group.The difference between the two groups was statistically significant( P<0.01). Conclusions:Plasma pyrocatechol has the potential to be metabolic marker of acute myocardial infarction in elderly patients and might be closely related to the occurrence and prognosis of this disease.

Spinal muscular atrophy, lower extremity-predominant, 2A (SMALED2A) is a form of spinal muscular atrophy, which predominantly affects muscles of the lower extremity, characterized by early childhood onset of muscle weakness and atrophy. This disorder is caused by mutation in the BICD2 gene. This paper reports a case of SMALED2A with recurrent skin ulceration of both feet. Whole exome sequencing of this case revealed a chr9∶95527083_A>AGCC insertion mutation in the 5’UTR of BICD2 gene.

Sleep apnea causes cardiac arrest, sleep rhythm disorders, nocturnal hypoxia and abnormal blood pressure fluctuations in patients, which eventually lead to nocturnal target organ damage in hypertensive patients. The incidence of obstructive sleep apnea hypopnea syndrome (OSAHS) is extremely high, which seriously affects the physical and mental health of patients. This study attempts to extract features associated with OSAHS from 24-hour ambulatory blood pressure data and identify OSAHS by machine learning models for the differential diagnosis of this disease. The study data were obtained from ambulatory blood pressure examination data of 339 patients collected in outpatient clinics of the Chinese PLA General Hospital from December 2018 to December 2019, including 115 patients with OSAHS diagnosed by polysomnography (PSG) and 224 patients with non-OSAHS. Based on the characteristics of clinical changes of blood pressure in OSAHS patients, feature extraction rules were defined and algorithms were developed to extract features, while logistic regression and lightGBM models were then used to classify and predict the disease. The results showed that the identification accuracy of the lightGBM model trained in this study was 80.0%, precision was 82.9%, recall was 72.5%, and the area under the working characteristic curve (AUC) of the subjects was 0.906. The defined ambulatory blood pressure features could be effectively used for identifying OSAHS. This study provides a new idea and method for OSAHS screening.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Humans ; Hypertension/complications* ; Polysomnography ; Sleep Apnea, Obstructive/diagnosis*