Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

OBJECTIVE To explore the effect of Xuanbai Chengqi Decoction on respiratory and oxygenation functions and the ex-pression levels of serum aquaporin(AQP)1 and AQP5 in patients with severe pneumonia complicated with gastrointestinal dysfunction of lung heat and fu-organ repletion type.METHODS 60 patients with severe pneumonia complicated with gastrointestinal dysfunc-tion of lung heat and fu-organ repletion type were randomly divided into control group and treatment group,with 30 cases each.The control group received standardized Western medicine treatment,and the treatment group was treated with Xuanbai Chengqi Decoction in addition to the control group.Both groups were treated for 7 d.The respiratory rate and oxygenation index,mechanical ventilation u-tilization rate,the clinical score including CURB-65 and CPIS scores,TCM syndrome score,gastrointestinal function indicators inclu-ding intra-abdominal pressure,serum gastrin(GAS)and vasoactive intestinal peptide(VIP),AQP1 and AQP5 levels were compared between the two groups before and after treatment.Ventilation utilization and ICU hospitalization days during treatment were compared between the two groups.RESULTS After treatment,compared with the control group,the respiratory rate,TCM syndrome score and intra-abdominal pressure in the treatment group were decreased significantly(P<0.05,P<0.01);meanwhile,the oxygenation index and the levels of serum GAS,AQP1 and AQP5 were increased significantly(P<0.05,P<0.01).CONCLUSION Xuanbai Chengqi Decoction can significantly improve clinical symptoms such as respiratory and oxygenation functions in patients,and its mechanism may be related to the regulation of AQP1 and AQP5.

Objective To explore high density lipoprotein(HDL)/low density lipoprotein(LDL)and total type Ⅰ collagen amino terminal extender peptide(t-PINP)/C-terminal peptide of type Ⅰ collagen β special sequence(β-CTX)and risk of os-teoporosis vertebral fractures(OPVFs)in elderly women.Methods The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed.According to whether or not fracture,patients were divided into non-fracture group(186 patients)and fracture group(260 patients).Univariate analysis was performed to analysis age,body mass index(BMI),N-terminal mioldle molecular fragment of osteocalcin,N-MID OC),t-PINP,β-CTX,25-hydroxyvitamin D[25-(OH)VitD],blood sugar(Glu),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),Ca,P,Mg,urea(UREA),creatinine(Cr)and Cystatin C(CysC),and correlation between OPVFs and the above indexes and lipid,bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL,t-PINP/β-CTX.Logistic regression was used to ana-lyze risk factors and stratification relationship between OPVFs and HDL/LDL,t-PINP/β-CTX.Results There were no signif-icant difference in age and BMI between non-fracture group and fracture group(P＞0.05).Compared with non-fracture group,contents of HDL,t-PINP/β-CTX and HDL/LDL in fracture group were decreased,and contents of β-CTX were increased(P＜0.05).OPVFs was positively correlated with β-CTX(r=0.110,P＜0.05),and negatively correlated with HDL,HDL/LDL and t-PINP/β-CTX(r=-0.157,-0.175,-0.181,P＜0.05).HDL and HDL/LDL were negatively correlated with β-CTX(r=-0.22,-0.12,P＜0.05)and t-PINP(r=-0.13,-0.10,P＜0.05).25-(OH)VitD was positively correlated with TC and HDL(r=0.11,0.18,P＜0.05).HDL/LDL was positively correlated with t-PINP/β-CTX(r=0.11,P=0.02).t-PINP/β-CTX[OR=0.998,95％CI(0.997,1.000),P＜0.05],HDL/LDL[OR=0.228,95％CI(0.104,0.499),P＜0.01]were risk factors for vertebral fracture.The lower levels between two tristratified indicators,the higher the vertebral fracture rate.The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum,with an adjusted OR was[2.112,95％CI(1.310,3.404)]and[2.331,95％CI(1.453,3.739)],respectively.Conclusion Serum low HDL/LDL and t-PINP/β-CTX are independent risk factors for OPVF in elderly women,and have good predictive value for OPVF risk.

Objective To analyze the diagnosis and treatment process of a pediatric patient with Crohn's disease(CD)who was treated with multiple biological agents,and to provide a reference for the treatment and pharmaceutical care.Methods The diagnosis and treatment process of the pediatric patient's disease was analyzed.Drug treatment plans were evaluated through literature research to identify the entry points for pharmaceutical care and medication guidance.Results Clinical pharmacist monitored the pediatric patient's adalimumab maintenance dose,efficacy,and adverse reactions through therapeutic drug monitoring.They recommended clinical adjustments to the maintenance dose of biological agents,so that the pediatric patients could benefit from multiple aspects such as efficacy,safety,and economy.Conclusion Clinical pharmacists should follow up with pediatric patients with CD,and pay attention to medication compliance and adverse reactions in those using biological agents.

Purpose::The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners.Methods::Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized.Results::There is a significant correlation observed between each criterion of skull and brain injury ( p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. Conclusion::The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory disease of the digestive tract with unknown etiology, complicated pathogenesis and diverse clinical manifestations.Biologic therapies, particularly anti-tumor necrosis factor-α antibodies, have fundamentally changed the treatment and course of IBD in children.In recent years, more biologics have been applied to pediatric IBD.This review summarizes the application of different biologics in pediatric IBD and elaborates on the latest research progress in their mechanism of action, efficacy, safety, clinical conversion and combined application, so as to improve the optimal treatment of IBD by pediatricians.

Objective:To explore the mechanism of miR-30e-5p inhibiting the invasion and migration of hepatoma cells by targeting phosphoinositide-3-kinase catalytic delta polypeptide(PIK3CD)-mediated phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of the rapamycin(mTOR)signaling pathway.Methods:HepG2 cells were divided into control group,miR-30e-5p mimics group,PIK3CD knockdown group,negative control group,and miR-30e-5p mimics+PIK3CD overexpression group by transfecting the corresponding plasmids,the expression of miR-30e-5p,PIK3CD and PI3K/AKT/mTOR signaling pathway was detected by qRT-PCR and Western blot;the proliferation rate of Hep G2 cells in each group was detected by CCK-8 method;cell migration and invasion were measured by cell scratch test and Transwell test;the expression of matrix metalloproteinase(MMP)2,MMP9,E-cadherin,N-cadherin,Vimentin in Hep G2 cells of each group were detected by Western blot.The targeting regulation of miR-30e-5p on PIK3CD in Hep G2 cells was detected by double luciferase report assay.Results:Compared with the control group,the proliferation rate,migration rate,invasion number,the expression of N-cadherin,MMP2 and MMP9 proteins,the expression of PIK3CD protein and mRNA,p-P13K/PI3K,p-AKT/AKT,and p-mTOR/mTOR in the miR-30e-5p mimics group and PIK3CD knockdown group were lower(P＜0.05),the expression of E-cadherin protein was higher(P＜0.05).Overexpression of PIK3CD attenuates the inhibitory effects of miR-30e-5p mimics on proliferation,migration and invasion of hepatocellular carcinoma cells and elevates the expression of PI3K/AKT/mTOR pathway-related proteins;miR-30e-5p targets down-regulation of PIK3CD expression.Conclusion:Up-regulation of miR-30e-5p can prevent PI3K/AKT/mTOR signal activation by decreasing the expression of PIK3CD,thereby inhibiting the proliferation,migration and invasion of hepatocellular carcinoma cells.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS’s pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS.Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.