OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.
Humans ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms/pathology* ; Lysine/metabolism* ; NF-kappa B/metabolism* ; TNF Receptor-Associated Factor 6/metabolism* ; Transcription Factor AP-1/metabolism* ; Ubiquitin/metabolism*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To master the epidemic trend of human brucellosis in Qinghai Province, so as to provide basis for scientific prevention and control of the disease.Methods:In 2019 and 2020, at the national and provincial brucellosis monitoring sites in Qinghai Province, a total of 18 counties (cities and districts, hereinafter referred to as counties), no less than 400 serum samples were sampled every year for brucellosis Rose-Bengal plate agglutination test (RBPT) and serum tube agglutination test (SAT), which would be tested and judged according to the criteria of "Diagnosis for Brucellosis" (WS 269-2019).Results:In 2019, a total of 1 612 people were monitored in national brucellosis monitoring sites, 93 were RBPT positive, 54 were SAT positive, 54 were diagnosed, and the prevalence rate was 3.35% (54/1 612). In 2020, 1 677 people were monitored in national brucellosis monitoring sites, 151 were RBPT positive, 80 were SAT positive, 80 were diagnosed, and the prevalence rate was 4.77% (80/1 677). There were significant differences in RBPT positive rate, SAT positive rate and prevalence rate among national monitoring sites between the two years (χ 2 = 12.52, 4.24, 4.24, P < 0.05). In 2019, a total of 6 043 people were monitored in provincial brucellosis monitoring sites, 128 were RBPT positive, 91 were SAT positive, 87 were diagnosed, and the prevalence rate was 1.44% (87/6 043). In 2020, 5 664 people were monitored, 108 were RBPT positive, 59 were SAT positive, 52 were diagnosed, and the prevalence rate was 0.92% (52/5 664). There was no significant difference in RBPT positive rate among provincial monitoring sites between the two years (χ 2 = 0.66, P = 0.416), and the differences in SAT positive rate and prevalence rate were statistically significant among provincial monitoring sites between the two years (χ 2 = 4.98, 14.57, P < 0.05). Conclusion:In 2019 and 2020, there are human brucellosis in national and provincial brucellosis monitoring sites in Qinghai Province.

Men who have sex with men (MSM) is a group of people at high risk for HIV infection in China, Pre-exposure prophylaxis (PrEP) is a bioprophylaxis strategy in the prevention of HIV infection in MSM, which can reduce the risk for HIV infection in this population effectively. However, in the paractice, the use level of PrEP in MSM is low in China, and there are MSM who know PrEP but receive no PrEP. This paper summarizes the current status of the awareness, willingness to use, actual use of PrEP in MSM and influencing factors both at home and abroad to provide a reference for the promotion of PrEP use in MSM in China.
Male ; Humans ; Pre-Exposure Prophylaxis ; Homosexuality, Male ; HIV Infections/prevention & control* ; Health Knowledge, Attitudes, Practice ; Sexual and Gender Minorities