This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is in-volved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregu-lation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatic-ally reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of hu-man STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Fur-thermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regula-ting the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a po-tential inhibitory factor affecting the occurrence and progression of STAD.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective:To explore the association between sleep and myopia among students aged 6-15 years in Tianjin.Methods:A cross-sectional study was conducted.A total of 218 864 primary and secondary school students aged 6-15 years in Tianjin were recruited from January 2023 to May 2023.Basic information and responses to the Children's Sleep Habits Questionnaire (CSHQ) were collected.Logistic regression models were used to assess the association between myopia and sleep.The study followed the Declaration of Helsinki, and the research protocol was approved by the Medical Ethics Committee of Tianjin Medical University Eye Hospital (No.ChiCTR2200065710). All questionnaires and demographic information were collected with parental consent.Results:It was found that 68 121(31.12%) students were myopic and 178 514(81.56%) had sleep disorders.The prevalence of myopia among students with average daily sleep durations of ≤8 hours, >8-9 hours, >9-10 hours, and >10 hours was 52.17%(9 288/17 803), 35.35%(31 037/87 787), 25.18%(24 481/97 216), and 20.64% (3 315/16 058), respectively, and the difference was statistically significant ( χ2=6 835.649, P<0.001). After adjusting for sex, age, body mass index, and potential confounding factors, compared with students with average daily sleep duration of >10 hours, students with average daily sleep durations of ≤8 hours ( OR=1.496, 95% CI: 1.415-1.581, P<0.001), >8-9 hours ( OR=1.364, 95% CI: 1.383-1.447, P<0.001), and >9-10 hours ( OR=1.257, 95% CI: 1.202-1.316, P<0.001) had a higher risk of myopia.Students with sleep disorders, bedtime resistance, sleep-onset delay, irregular sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness were more likely to be myopic. Conclusions:Sleep is a key factor influencing myopia among schoolchildren aged 6-15 years in Tianjin.

Objective:To explore the association between sleep and myopia among students aged 6-15 years in Tianjin.Methods:A cross-sectional study was conducted.A total of 218 864 primary and secondary school students aged 6-15 years in Tianjin were recruited from January 2023 to May 2023.Basic information and responses to the Children's Sleep Habits Questionnaire (CSHQ) were collected.Logistic regression models were used to assess the association between myopia and sleep.The study followed the Declaration of Helsinki, and the research protocol was approved by the Medical Ethics Committee of Tianjin Medical University Eye Hospital (No.ChiCTR2200065710). All questionnaires and demographic information were collected with parental consent.Results:It was found that 68 121(31.12%) students were myopic and 178 514(81.56%) had sleep disorders.The prevalence of myopia among students with average daily sleep durations of ≤8 hours, >8-9 hours, >9-10 hours, and >10 hours was 52.17%(9 288/17 803), 35.35%(31 037/87 787), 25.18%(24 481/97 216), and 20.64% (3 315/16 058), respectively, and the difference was statistically significant ( χ2=6 835.649, P<0.001). After adjusting for sex, age, body mass index, and potential confounding factors, compared with students with average daily sleep duration of >10 hours, students with average daily sleep durations of ≤8 hours ( OR=1.496, 95% CI: 1.415-1.581, P<0.001), >8-9 hours ( OR=1.364, 95% CI: 1.383-1.447, P<0.001), and >9-10 hours ( OR=1.257, 95% CI: 1.202-1.316, P<0.001) had a higher risk of myopia.Students with sleep disorders, bedtime resistance, sleep-onset delay, irregular sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness were more likely to be myopic. Conclusions:Sleep is a key factor influencing myopia among schoolchildren aged 6-15 years in Tianjin.

Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is in-volved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregu-lation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatic-ally reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of hu-man STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Fur-thermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regula-ting the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a po-tential inhibitory factor affecting the occurrence and progression of STAD.

OBJECTIVE To analyze the clinical characteristics and pathogens for mixed infections in children with pertussis,so as to references for clinical diagnosis and treatment.METHODS A retrospective analysis was conduc-ted on the clinical data of 350 children diagnosed with pertussis and hospitalized in Wuhan Children's Hospital from Jan.2022 to Dec.2023.The clinical characteristics,peak white blood cell count,peak lymphocyte ratio,high-sensitivity C-reactive protein or C-reactive protein,procalcitonin and complications were compared between different age groups,as well as between the single infection group and the mixed infection group.RESULTS Mixed infections were observed in 291 children(83.14％),predominantly viral(63.43％,222/350),with human rhinovirus/enterovirus being the most common(32.57％,114/350).For children aged＜6 months,6 months to＜1 year and 1 to＜3 years,the incidence of family contact history of cough,panting,hasty breathing,respira-tory failure,peak white blood cell count and peak lymphocyte ratio were all higher than those aged 3 to＜6 years and≥6years(all P＜0.05).The incidence of post-cough vomiting was higher in children aged 6 months to＜1 year and 1 to＜3 years compared to other age groups(P＜0.05).The length of hospital stay decreased with in-creasing age(P＜0.05).The proportions of children with paroxysmal spasmodic cough,post-cough cyanosis,post-cough flushing,coughing spells,inspiratory three concave sign,pneumonia and pulmonary phlegm rales all generally decreased with age(all P＜0.05).Nodding respiration was only observed in children aged＜1 year(P＜0.05).The incidence of fever,co-infection with bacteria and Mycoplasma pneumoniae infection was higher in children aged 6 months to＜1 year,1 to＜3 years,3 to＜6 years and ≥ 6 years compared to those aged＜6 months(all P＜0.05).The incidence of fever was higher in the mixed infection group than that in the single in-fection group(P＜0.05).Children in the single infection group had longer hospital stays,higher incidence of par-oxysmal spasmodic cough,nocturnal cough,post-cough flushing,coughing spells,pulmonary phlegm rales and higher peak lymphocyte ratio(all P＜0.05).The incidence of paroxysmal spasmodic cough was higher in the sin-gle infection group for children aged＜3 months(P＜0.05).CONCLUSIONS The younger children with pertussis have a higher proportion of family contact history of cough and are more prone to clinical manifestations such as paroxysmal spasmodic cough,post-cough vomiting,post-cough cyanosis,and pneumonia.They also have higher peak white blood cell counts,peak lymphocyte ratios and longer hospital stays.As children'age increased,the in-cidence of fever,bacterial,and mycoplasma infections also increased.The types of pathogens in mixed infections varies with patients' age and pertussis mixed infections may mask typical clinical symptoms.