BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective To explore the efficacy of single and combined parameters from 4 non-Gaussian diffusion models for differentiating breast imaging reporting and data system(BI-RADS)MRI category 4 benign and malignant breast tumors.Methods A total of 161 BI-RADS MRI category 4 breast lesions from 159 patients were retrospectively enrolled.Based on pathological results,the lesions were divided into malignant group(n=132)and benign group(n=29).The apparent diffusion coefficient(ADC)values were calculated from diffusion weighted imaging(DWI)sequences.Multi-b-value diffusion imaging data were acquired and fitted using 4 non-Gaussian models to obtain respective parameters,including diffusion kurtosis imaging(DKI),stretched exponential model(SEM),continuous-time random walk(CTRW)and fractional order calculus(FROC)model.Univariable and multivariable logistic regression analyses were employed to identify the diffusion quantitative indicators useful for differentiating benign and malignant BI-RADS MRI category 4 breast tumors.Receiver operating characteristic(ROC)curves were drawn,and the optimal threshold was determined using Youden index.The differentiating performance of ADC value,single parameter and their combination from non-Gaussian diffusion models were assessed and compared according to the area under the curve(AUC)of ROC curves,as well as the sensitivity,specificity and accuracy under the optimal thresholds.Results In malignant group,αCTRW,KDKI and μFROC values were higher,while ADC,DCTRW,DFROC,DDCSEM,αSEM and DDKI values were lower than those in benign group(all P＜0.05).Multivariable logistic regression analysis identified DCTRW and αCTRW values as independent factors for differentiating benign and malignant BI-RADS MRI category 4 breast tumors(both P＜0.05),and a combined model was then constructed.The AUC of the combined model was higher than that of each single parameter including ADC,DCTRW and αCTRW values(all P＜0.05).Conclusion The combined model of DCTRW and αCTRW had better efficacy than each single parameter for differentiating benign and malignant BI-RADS MRI category 4 breast tumors.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

We reported the clinical,imaging,and treatment process of a patient with severe cranial penetrating injury caused by a nail from a nail gun that accidentally shot into the eye and penetrated into the skull while working.The patient was admitted to the Qingpu Branch of Zhongshan Hospital,Fudan University after being injured by the nail gun.The patient was admitted to the hospital 1 hour after injury with coma.After admission,the foreign body was completely removed and part of the hematoma was cleared through emergency surgery.After surgery,there were high-risk complications such as cerebral edema peak,intracranial hypertension,intracranial infection,cerebrospinal fluid leakage,and intracranial pseudoaneurysm.The patient eventually regained consciousness and was transferred to rehabilitation treatment.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective:To explore the changes in plasma lipoprotein associated phospholipase A2(Lp-PLA2)and silencing information regulatory protein 1(SIRT1)in patients with sepsis complicated with acute kidney injury(AKI)and their relationship with short-term prognosis.Methods:243 sepsis patients who received treatment in our hospital from May 2022 to May 2024 were prospective selected,including 80 sepsis patients with AKI(AKI group)and 163 sepsis patients without AKI(non AKI group),the plasma Lp-PLA2 and SIRT1 levels between the two groups were compared.They were divided into good prognosis group and poor prognosis group according to 28 d prognosis after admission in AKI group.The influencing factors of short-term prognosis in sepsis patients complicated with AKI were analyzed by multiple logistic regression model.The short-term prognostic value of plasma Lp-PLA2 and SIRT1 alone and in combination for sepsis complicated with AKI patients was analyzed using receiver operating characteristic(ROC)curve.Results:Compared with non AKI group,AKI group had higher Lp-PLA2 and lower SIRT1(P＜0.05).39 deaths within 28 d after admission in AKI group(poor prognosis group),41 cases survived(good prognosis group),with poor prognosis rate of 48.75％(39/80).Sequential organ failure assessment(SOFA)score,acutephysiology and chronic health evaluationⅡ(APACHEⅡ)score,creatinine(Scr),lactate dehydrogenase albumin ratio(LAR)in poor prognosis group were higher than those in good prognosis group,while procalcitonin(PCT)was lower than that in good prognosis group(P＜0.05).Compared with the good prognosis group,poor prognosis group had higher Lp-PLA2 and lower SIRT1 at admission(P＜0.05).Elevated SOFA score,elevated Scr,elevated APACHEⅡ score,and elevated plasma Lp-PLA2 were risk factors for poor prognosis in sepsis patients complicated with AKI(P＜0.05),while elevated plasma SIRT1 was a protective factor(P＜0.05).ROC curve analysis results showed that,the combined detection of plasma Lp-PLA2 and SIRT1 predicted a poor prognosis for sepsis patients with AKI with an area under the curve(AUC)of 0.935,which was better than the prediction of 0.813 and 0.858 for plasma Lp-PLA2 and SIRT1 alone.Conclusion:Sepsis complicated with AKI patients have elevated plasma Lp-PLA2 and decreased SIRT1,combined detection of the two can assist in predicting the risk of poor prognosis.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To investigate the effect of early high-sucrose diet (eHSD) on cognitive function and its regulatory mechanism in 3×Tg-AD mice.Methods:(1) Eighteen specific-pathogen-free (SPF)-grade 2-month-old wide-type (WT) mice were randomly divided into a WT+normal chow diet (NCD) group and a WT+eHSD group, with 9 mice in each group; and 18 SPF-grade 2-month-old 3×Tg-AD mice were randomly divided into a 3×Tg-AD+NCD group and a 3×Tg-AD+eHSD group, with 9 mice in each group. At 2-5 months old, mice in the 4 groups received standard laboratory food+purified water or 30% sucrose water, followed by standard feed for all groups. At 8 months old, cognitive function was assessed by Morris water maze test; fluorescent intensity of AT8 (phosphorylated [p]-tau) and T22 (tau oligomers) in the hippocampal tissues was detected by immunofluorescent staining; concentrations of β-amyloid protein (Aβ) 42 and Aβ 40 were detected by enzyme-linked immunosorbent assay (ELISA); protein expressions of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), p-TBK1, and CCAAT/enhancer-binding protein β (C/EBPβ) were detected by Western blotting; activity of C/EBPβ transcription factor was detected by activity assay; mitochondrial DNA (mtDNA) content in the cytoplasm of cell was detected by real-time quantitative PCR (qPCR). (2) Eighteen SPF-grade 2-month-old 3×Tg-AD mice were randomized into a 3×Tg-AD+eHSD+H-151 group and a 3×Tg-AD+eHSD+dimethyl sulfoxide (DMSO) group, with 9 mice in each group. Mice at 2-5 months old were given standard laboratory food+30% sucrose water; they were, respectively, injected intraperitoneally with STING pathway inhibitor H-151 or DMSO at 5 months old, and continually injected until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, Western blotting and C/EBPβ transcription factor activity experiments were repeated as before. (3) After crossing C/EBPβ heterozygous knockout (C/EBPβ +/-) mice with 3×Tg-AD mice, 3×Tg-AD/C/EBPβ +/- mice were obtained, and 3×Tg-AD mice were used as controls; they were named 3×Tg-AD/C/EBPβ +/-+eHSD group and 3×Tg-AD+eHSD group, with 9 mice in each group. Both groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old, followed by standard feed until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. (4) C/EBPβ transgenic mice (C/EBPβTg) were crossed with 3×Tg-AD mice to obtain C/EBPβTg/3×Tg-AD mice, and Non-Tg/3×Tg-AD mice were used as controls; they were, respectively, named as C/EBPβTg/3×Tg-AD+eHSD+H-151 group, Non-Tg/3×Tg-AD+eHSD+H-151 group, and Non-Tg/3×Tg-AD+eHSD+DMSO group, with 9 mice in each group. All 3 groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old; at 5-8 months old, mice in the C/EBPβTg/3×Tg-AD+eHSD+H-151 group and Non-Tg/3×Tg-AD+eHSD+H-151 group were intraperitoneally injected with H-151, while mice in the Non-Tg/3×Tg-AD+eHSD+DMSO group were injected with DMSO; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. Results:(1) Compared with those in the WT+NCD group and WT+eHSD group, area under the latency curve of 3×Tg-AD+eHSD mice was significantly increased, and proportion of time spending in the targeted quadrant of mice in the 3×Tg-AD+NCD group and 3×Tg-AD+eHSD group was significantly decreased ( P<0.05); compared with that in the 3×Tg-AD+NCD group, proportion of time spending in the targeted quadrant in mice of the 3×Tg-AD+eHSD group was significantly reduced ( P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.076 vs. 2.902±0.399; T22 fluorescent intensity: 1.000±0.145 vs. 2.495±0.273; Aβ 42: 1.000±0.167 vs.1.956±0.132; Aβ 40: 1.000±0.226 vs.1.900±0.116), significantly increased C/EBPβ protein expression and C/EBPβ transcription factor activity (1.000±0.164 vs. 1.804±0.112; 1.000±0.216 vs. 2.743±0.301), and statistically increased mtDNA level detected by D-loop1 and D-loop3 (1.000±0.234 vs. 2.800±0.210; 1.000±0.155 vs. 2.952±0.078; P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.192 vs. 2.093±0.081; p-TBK1/TBK1: 1.000±0.148 vs. 1.561±0.112, P<0.05). (2) Compared with the 3×Tg-AD+eHSD+DMSO group, the 3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers expressions, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.142 vs. 0.538±0.057; T22 fluorescent intensity: 1.000±0.104 vs. 0.665±0.088; Aβ 42: 1.000±0.084 vs. 0.600±0.007; Aβ 40: 1.000±0.138 vs. 0.476±0.083), significantly decreased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.054 vs. 0.468±0.111; p-TBK1/TBK1: 1.000±0.057 vs. 0.598±0.090), and significantly decreased C/EBPβ transcription factor activity (1.000±0.097 vs. 0.445±0.106; P<0.05). (3) Compared with the 3×Tg-AD+eHSD group, the 3×Tg-AD/C/EBPβ +/-+eHSD group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.160 vs. 0.506±0.065; T22 fluorescent intensity: 1.000±0.127 vs. 0.346±0.048; Aβ 42: 1.000±0.017 vs. 0.510±0.101; Aβ 40: 1.000±0.098 vs. 0.586±0.153), and significantly decreased C/EBPβ protein expression (1.000±0.101 vs. 0.568±0.094; P<0.05). (4) Compared with the Non-Tg/3×Tg-AD+eHSD+DMSO group, the Non-Tg/3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, and significantly decreased p-tau and tau oligomers expressions, Aβ 40 concentration in the hippocampus, and the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly decreased STING protein expression and p-TBK1/TBK1 ratio in the hippocampus ( P<0.05). Compared with the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly increased area under the latency curve, significantly decreased proportion of time spending in the targeted quadrant, and significantly increased p-tau and tau oligomers expressions, Aβ 40 and Aβ 42 concentration in the hippocampus ( P<0.05). Conclusion:The eHSD aggravates cognitive impairment in 3×Tg-AD mice through activating cGAS-STING-C/EBPβ pathway.