Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

Objective To understand the disease acceptance status and related factors in human immunodeficiency virus(HIV)-infected/acquired immunodeficiency syndrom(AIDS)patients,so as to guide the clinical development of intervention measures,and to provide empirical evidence for improving clinical outcomes.Methods Convenience sampling method was used to select 555 HIV-infected/AIDS patients who received treatment in the designated AIDS treatment clinic of a hospital.General data,disease acceptance,disease self-management efficacy and clinical out-comes(such as quality of life,CD4+T lymphocyte count and HIV viral load)of the studied subjects were collected.Results The average disease acceptance of HIV-infected/AIDS patients was(26.08±5.34)points.Multiple linear regression analysis showed that religious belief and self-management efficacy were related factors affecting the di-sease acceptance of patients(both P＜0.05),which could explain the 30.4％variation in disease acceptance of HIV-infected/AIDS patients,and the disease acceptance of patients was closely related to their quality of life(P＜0.001).Conclusion HIV-infected/AIDS patients have a moderate level of disease acceptance.Medical staff should fully consider patients'religious beliefs and self-management efficacy,so as to formulate targeted intervention mea-sures to improve patients'acceptance of disease,and further promote patients'quality of life.

ObjectiveTo investigate the trends in diabetes mortality rate and the characteristics of decreased population in Fengxian District, Shanghai from 2012 to 2021. MethodsData from the death registration records of the residents in Fengxian District between 2012 and 2021, sourced from the Shanghai Death Surveillance System, were analyzed. Indicators such as the crude mortality rate due to diabetes, the standardized mortality rate, years of life lost (YLL), and the probability of premature death were estimated. Annual percentage change (APC) was used to analyze the temporal trends of mortality and the probability of premature death due to diabetes. Rate decomposition analysis was used to assess the contributions of demographic and non-demographic factors to diabetes mortality. ResultsFrom 2012 to 2021, there were 1 471 deaths due to diabetes in Fengxian District, with a crude mortality rate of 27.51/100 000 and a standardized mortality rate of 17.58/100 000. The crude mortality rate showed an overall increasing trend (APC=4.58%, Z=3.49, P<0.05). The potential years of life lost (PYLL) due to diabetes over this period amounted to 9 715 person-years, with a PYLL rate of 1.82 ‰, and the average years of life lost (AYLL) was 11.94 years. The probability of premature death was 0.41% (APC=3.36%, t=2.33, P<0.05). Both population aging and non-aging factors contributed to the increase in diabetes mortality, with overall contribution rates of 67.99% and 32.01%, respectively. Among men, the contribution rates were 60.57% and 39.43%, while among women, they were 79.43% and 20.57%, respectively. ConclusionFrom 2012 to 2021, both the crude mortality rate and the probability of premature death due to diabetes showed an upward trend among the residents in Fengxian District, with a higher YLL. Population aging was the main factor causing the increase in mortality rate, while non-demographic factors had a greater impact on the rise in diabetes mortality among men than that in women. Therefore, the management on male diabetes patients should be strengthened.

Objective:To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes(MDS)with RUNX1 gene mutation.Methods:Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology,the Second Affiliated Hospital of Air Force Military Medical University from October 1,2015 to October 31,2022 were retrospectively analyzed.Gene mutation detection was performed by second-generation sequencing technology,and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed.Results:A total of 30 cases(16.95％)of RUNX1 gene mutations were detected,including 15 missense mutations(50.0％),9 frameshift deletion mutations(30.0％),4 splice site mutations(13.3％),1 insertion mutation(3.3％),and 1 nonsense mutation(3.3％).Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis(range:62.25-78.50 years old).There were no significantly differences between RUNX1 mutations and wild type patients in age distribution,gender,peripheral blood white blood cell count,hemoglobin level,bone marrow and peripheral blood blasts ratio,IPSS-R cytogenetics,IPSS-R stage,etc.(P＞0.05).However,there were statistically significant differences in platelet count and whether complicated karyotype.Compared with patients without RUNX1 gene mutation,patients with RUNX1 gene mutation had lower platelet count(P=0.018),and were less likely to have complicated karyotype at initial diagnosis(P=0.01).Cox proportional hazards model analysis showed that when other co variates remained unchanged,the higher the platelet count,the better the survival of patients(HR=0.995,95％CI:0.990-0.999,P=0.036);In the IPSS-M prognostic stratification,keeping other covariates unchanged,the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group(HR=0.149,95％CI:0.031-0.721,P=0.018;HR=0.026,95％CI:0.003-0.234,P=0.001).Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time(P＜0.001).Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group.RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients.Conclusion:RUNX1 gene mutation is an adverse prognostic factor in MDS patients,especially in the IPSS-M prognosis stratification group of low-risk,medium-low risk,medium-high risk and WHO classification of early patients.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Objective:To evaluate the effect of different doses of compound sodium chloride injection combined with norepinephrine on prevention of hypotension after lumbar anesthesia in the patients undergoing caesarean section.Methods:A total of 150 patients with a singleton fetus, aged 18-45 yr, at ≥37 weeks of gestation, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with height ≥150 cm, weighing ≤100 kg, with body mass index < 40 kg/m 2, scheduled for elective caesarean section under lumbar anesthesia, were divided into 3 groups ( n=50 each) by the random number table method: compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 groups (group A, group B, group C). Compound sodium chloride injection 4 ml/kg was intravenously injected for liquid preload before lumbar anesthesia, and 0.5% hyperbaric bupivacaine 12.5 mg was injected to the subarachnoid space for lumbar anesthesia. Norepinephrine was intravenously injected at a dose of 6 μg immediately after intrathecal injection, followed by an infusion of 0.05 μg·kg -1·min -1, and infusion was stopped at 5 min after delivery. Compound sodium chloride injection was intravenously infused simultaneously at a rate of 4, 8 and 12 ml·kg -1·h -1 in A, B and C groups, respectively. The maximum diameter of inferior vena cava (IVCmax) and the minimum diameter of inferior vena cava (IVCmin) were measured by ultrasound, and inferior vena cava collapse index (IVC-CI) was calculated at 1 min before fluid preload (T 1), immediately after fluid preload (T 2), at 5 min after anesthesia (T 3), at 5 min after fetal delivery (T 4) and immediately before leaving the operating room (T 5). The incidence of intraoperative adverse events (hypotension, severe hypotension, bradycardia, hypertension, nausea, and vomiting) and neonatal outcomes (umbilical artery blood gas index and Apgar score at 1 and 5 min after birth) were recorded. Results:Compared with group A, IVCmin was significantly increased and IVC-CI was decreased at T 5 in group B, and IVCmin and IVCmax were significantly increased and IVC-CI was decreased at T 5 in group C ( P<0.05). There was no significant difference in IVCmax, IVCmin and IVC-CI at each time point between group B and group C ( P>0.05). There was no significant difference in the incidence of hypotension, severe hypotension, bradycardia, hypertension, nausea and vomiting among the three groups ( P>0.05). There was no significant difference in the results of blood gas analysis of the umbilical artery and Apgar score at each time point after birth among the three groups ( P>0.05). Conclusions:Compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 combined with norepinephrine can effectively prevent the occurrence of hypotension after lumbar anesthesia in the patients undergoing caesarean section without increasing maternal and infant adverse events, and the effect of 8 and 12 ml·kg -1·h -1 for volume supplementation is better than that of 4 ml·kg -1·h -1.

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.
Female ; Male ; Pregnancy ; Animals ; Mice ; Arachidonic Acid ; Ovarian Reserve ; Proteomics ; Ovary ; Lipid Metabolism

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.
Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; B7-H1 Antigen/metabolism* ; Lymphocytes, Tumor-Infiltrating/pathology* ; Carcinoma ; Tumor Microenvironment ; Triple Negative Breast Neoplasms/pathology* ; Prognosis ; Biomarkers, Tumor/metabolism*

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q₁, Q₃) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q₁, Q₃) of 42 (20, 55) and the median exposure period (Q₁, Q₃) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
Male ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology* ; Incidence ; Family Characteristics