This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Objective To explore the expression of serum long noncoding RNA(lncRNA)CCDC18-AS1 and microRNA-501(miR-501)in patients with human papillomavirus(HPV)-infected cervical cancer,and its correlation with prognosis.Methods A total of 78 patients with HPV-infected cervical cancer who underwent treatment in the hospital from May 2019 to May 2020 were enrolled as study group,meantime,80 patients with simple HPV infection and 81 patients with simple non-HPV infected cervical cancer were set as control group 1 and control group 2.Serum lncRNA CCDC18-AS1 and miR-501 expression levels were detected by re-al-time quantitative PCR.Then the clinical features,postoperative overall survival and progression-free surviv-al were analyzed in the study group.Results The relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in the study group were higher than those in control group 1 and control group 2(P<0.05),and the relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in control group 2 were higher than those in control group 1(P<0.05).Pearson correlation analysis showed that serum lncRNA CCDC18-AS1 and miR-501 were positively correlated in the study group(r=0.421,P<0.001).Serum lncRNA CCDC18-AS1 and miR-501 in study group were not related to age,but were related to clinical stage,differentiation de-gree,lymph node metastasis,and squamous epithelial cell antigen(P<0.05).Kaplan Meier analysis showed that the postoperative overall survival and progression-free survival of high lncRNA CCDC18-AS1 and miR-501 expression groups were shorter than those of low expression groups(P<0.05).Conclusion HPV-infec-ted cervical cancer patients have up-regulated expression of serum lncRNA CCDC18-AS1 and miR-501,and the abnormal changes are closely related to patients'clinical characteristics and postoperative survival,so the two indicators could be used as auxiliary indicators for the disease assessment and prognosis evaluation.

Objective To analyze the effect of low-dose methylprednone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase(LDH)in children.Methods Children with Mycoplasma pneumoniae pneumonia(MPP)complicated with elevated LDH were divided into control group and treatment group by random number table method.The control group was given erythromycin treatment,and the treatment group was given low-dose methylprednisolone sodium succinate combined with erythromycin treatment.Clinical efficacy and clinical symptom disappearance time were recorded in both groups.Pulmonary X-ray signs,immune function[T cell subsets(CD4+,CD8+,CD4+/CD8+)],immunoglobulin(Ig)A,IgM and serum LDH were compared between the two groups before and after treatment,and the adverse drug reactions of treatment were observed.Results There were 51 cases in control group and 51 cases in treatment group.The total effective rate in treatment group was 96.00％,which was significantly higher than 81.63％in control group(P＜0.05).The fever abatement times in treatment group and control group were(4.22±0.87)and(5.46±0.98)d;cough disappearance times were(6.31±0.98)and(7.49±1.10)d;disappearance times of pulmonary rales were(7.36±1.14)and(8.61±1.23)d,all with significant difference(all P＜0.05).After treatment,the patchy infiltrating shadow sign rates in treatment group and control group were 2.00％and 16.33％;the bronchial wall thickening sign rates were 4.00％and 18.37％,all with significant difference(all P＜0.05).After treatment,IgA levels in treatment group and control group were(0.55±0.11)and(0.68±0.12)g·L-1;IgM levels were(0.90±0.19)and(1.18±0.21)g·L-1;LDH levels were(229.45±10.30)and(240.18±11.17)U·L-1,all with significant difference(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.00％and 4.08％respectively,without significant difference(P＞0.05).Conclusion Erythromycin combined with low-dose methylprednone in systemic treatment of children with MPP and elevated LDH has a significant efficacy,and it can promote the reductions of inflammation and immune disorders and accelerate the disease outcomes,and it is safe and reliable.

Aim To investigate the influence of different concentrations of dextran sulfate sodium (DSS) and administration approaches on the establishment of mouse model of acute ulcerative colitis(UC). Methods Mice were randomly divided into the normal control group, 3% DSS free drinking group, 4% DSS free drinking group, 30% DSS intragastric administration group and 40% DSS intragastric administration group. The amount and average dosage of intaken DSS by mice in free drinking group were measured and the intragastric administration group were given the same dosage. The survival rate, disease activity index (DAI), the lengths and pathological changes of colon were observed, and the coefficients of variation of each indicator described above were compared among the groups. Results Except for the normal control group, other groups developed experimental UC. Among these four approaches, 3% DSS solution free drinking showed appropriate incidence, higher animal survival rate and operability and lower cost, while there was no significant difference in the coefficients of variation of DAI between 3% DSS solution free drinking group and the others. Conclusion 3% DSS solution free drinking has more advantages in the establishment of a murine model with acute UC than other approaches.

【Objective】 To investigate the temperament factor scores and typing characteristics in infants with early eczema, aiming to provide evidence for early intervention in infant eczema. 【Methods】 It was a retrospective and 1: 2 matched case-control study. Using the domestic standardized Early Infancy Temperament Questionnaire(EITQ), we evaluated the temperament factor scores and temperament types of 56 one-month-old eczema infants and 112 healthy infants and then compared the results. 【Results】 The distribution of temperament types is featured with significantly higher proportion of the male infants with D type and I-D type but significantly lower proportion of the male infants with E type and I-E type in the eczema group compared with those in the control group(all P<0.001). Univariate logistic regression analysis of temperament dimension demonstrated that activity, rhythmicity, adaptability and intensity were the influencing factors of eczema (all P<0.05). Multivariate logistic regression analysis(backward stepwise) of temperament dimension showed that adaptability and intensity were the independent influencing factors, and infants in eczema group had strong adaptability and weak intensity. 【Conclusion】 Infants with early eczema have strong adaptability and weak intensity, we should provide early intervention based on their temperament characteristics.

BACKGROUND: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. METHODS: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. RESULTS: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. CONCLUSIONS The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.
Adult ; Cardiomyopathy, Hypertrophic ; physiopathology ; therapy ; Death, Sudden, Cardiac ; prevention & control ; Defibrillators, Implantable ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Tachycardia, Ventricular ; physiopathology ; therapy

Objective To analyze the epidemiological characteristics of dengue fever outbreak in Shaoxing City,and to provide a scientific basis for the prevention and control.Methods A retrospective epidemiological investigation was conducted to search the patients by given definition.Enzyme linked immunosorbent assay (ELISA)was used for detecting the anti -dengue virus antibodies.The serum samples from patients were collected for dengue virus isolation and the positive samples were identified by RT -PCR.Breteau Index was carried out to monitor the density of mosquito larva. Results A total of 42 cases were found with no death reported.The symptoms mainly included fever (1 00%),fatigue (59. 52%),arthralgia(50. 00%),headache (47. 62%)and rash (38. 1 0%).The outbreak lasted for 71 days with the first case occurred in July 1 5 and the last in September 23.The peak was from August 30 to September 5. Thirty seven cases were located in Keqiao District and 5 cases were in Yuecheng District.The male/female ratio was 1 . 33∶1 .The age of cases ranged from 1 0 to 79 years old with the 40 -(1 9. 05%)and 50 -(1 9. 05%)age group making the largest proportion.The outbreak also showed family aggregation.IgM antibody and nucleic acid of dengue virus were detected from serum samples of 1 2 patients.The sequence of the isolation indicated that this outbreak was caused by dengue virus typeⅡ.Conclusion The imported cases,high density of mosquito vector and missed diagnosis might contribute to this outbreak.Developing a practical scheme for mosquito elimination,improving diagnostic capacity of medical staff and their consciousness of reporting could be important ways to control dengue fever.

AlM:To compare the efficacy and safety of latanoprost and brimonidine in the treatment of open angle glaucoma, and provide reference for rational drug use.METHODS:A total of 121 cases ( 136 eyes ) who were diagnosed as primary open angle glaucoma were selected in this study, and they were randomly divided into experimental group (62 cases, 70 eyes) and control group ( 59 cases, 66 eyes) according to different drug treatment. Patients in the control group received brimonidine eye drops twice a day, while patients in the experimental group received latanoprost eye drops once a day. The intraocular pressure, visual acuity and adverse reactions were checked of the two groups in the following 3mo.RESULTS:The intraocular pressure of patients in the control group was 18. 1 ± 1. 3mmHg, while the experimental group was 17. 0 ± 0. 9mmHg after 12wk of treatment, which were both lower than before (P<0. 05). The fluctuation of intraocular pressure in the experimental group was significantly lower than that of the control group. There was no significant difference in the LogMAR visual acuity between before and after treatment in the control group, while the LogMAR visual acuity of the experimental group was significantly improved. The control group had hyperemia, burning sensation, tearing, eyelid edema and other adverse side effects, and the experimental group had little adverse reactions. CONCLUSlON: Latanoprost can significantly reduce intraocular pressure in glaucoma patients with in the follow- up time, and reduce the impact of elevated intraocular pressure in the vision of glaucoma patients, with little adverse reaction, worthy of clinical application.

OBJECTIVETo discuss the effect of calcitonin gene-related peptides (CGRP) on epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs) in vitro.

METHODSThe effect of CGRP on E-cd protein and mRNA expression in both normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR. The signal transduction pathways of CGRP were observed by using protein kinase C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).

RESULTSCGRP increased E-cd mRNA and protein expressions of normal and O3-challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of CGRP on E-cd expression was partly abolished.

CONCLUSIONCGRP increased in cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose-dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC and CaM pathways.

Bronchi ; cytology ; Cadherins ; metabolism ; Calcitonin Gene-Related Peptide ; administration & dosage ; pharmacology ; Cell Line ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Ozone ; RNA, Messenger ; genetics

OBJECTIVETo explore the anti-aging effect of artemisia burning products (ie. smoke of moxibustion) and its proper intervention parameters.

METHODSAccording to factorial experiment design, 70 SAMP8 mice were randomly divided into one model group (group M) and 6 intervention groups: low concentration with 15 min group (group A1), low concentration with 30 min group (group A2), middle concentration with 15 min group (group B1), middle concentration with 30 min group (group B2), high concentration with 15 min group (group C1), high concentration with 30 min group (group C1). There were 10 cases in each group. Ten age-matched SAMR1 mice were used as normal group (group Z). All the mice in the 6 intervention groups were fumed with artemisia burning products of different concentration and time. The content of serum malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and glutathione reductase (GSH-Px) were tested.

RESULTSMDA content in group M was significantly higher than that in group Z (both P < 0.05), while SOD and GSH-Px activity were significantly lower in group M than that in group Z (both P < 0.05). Results of MDA, SOD and GSH-Px in 6 intervention groups were either of no statistically significant differences, or better than that in group M. Among 6 intervention groups, results of MDA and GSH-Px were better in group B1, while the result of SOD was better in group B2. Time factor didn't make any difference, while concentration of artemisia burning products is meaningful. As to SOD and GSH-Px, there's a strong interaction between the two factors.

CONCLUSIONWith certain concentration and time period, the intervention of artemisia burning products can exert anti-aging effect by increasing antioxydative capability and reducing metabolites of free radicals. Middle concentration and 30 minutes are recommended when intervened with artemisia burning products.

Aging ; blood ; metabolism ; Animals ; Antioxidants ; metabolism ; Artemisia ; chemistry ; Disease Models, Animal ; Glutathione Peroxidase ; blood ; Glutathione Reductase ; blood ; Humans ; Male ; Malondialdehyde ; blood ; Mice ; Moxibustion ; Superoxide Dismutase ; blood