Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective:To explore the characteristics of nail fold microcirculation in hemodialysis patients and its correlation with cardiovascular events.Methods:The clinical data of 185 patients undergoing regular hemodialysis in Dongguan Donghua Hospital from January 2017 to December 2021 were retrospectively analyzed. Among them, there were 76 cases of cardiovascular events (cardiovascular events group) and 109 cases of no cardiovascular events (non-cardiovascular events group). The nail fold microcirculation detector was used to detect the nail fold microcirculation of the first row of capillaries in the nail fold dermal papilla of the left ring finger. The nail fold microcirculation indexes and morphology integral, flow integral, loop integral, total integral were recorded. The general information and laboratory indexes (peripheral venous blood) were recorded. The value of total integral of nail fold microcirculation in predicting the cardiovascular events in hemodialysis patients was evaluated using the receiver operating characteristics (ROC) curve.Results:The age, proportion of hypertension, proportion of diabetes, C-reactive protein (CRP), alkaline phosphatase and N-terminal pro-brain natriuretic peptide (NT-ProBNP) in cardiovascular events group were significantly higher than those in non-cardiovascular events group: 58 (44, 69) years vs. 49 (40, 63) years, 97.4% (74/76) vs. 83.5% (91/109), 43.4% (33/76) vs. 24.8% (27/109), 9.02 (2.73, 11.70) mg/L vs. 3.76 (1.28, 11.70) mg/L, 82 (75, 97) U/L vs. 72 (59, 82) U/L and 2 652 (1 020, 5 359) ng/L vs. 1 894 (780, 4 601) ng/L, the creatinine and triglyceride (TG) were significantly lower than those in non-cardiovascular events group: (961.95 ± 277.11) μmol/L vs. (1 058.93 ± 284.66) μmol/L and (1.73 ± 1.02) mmol/L vs. (2.27 ± 2.02) mmol/L, and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in gender composition, dialysis age, dialysis time, dialysis pathway, blood routine, serum iron, serum ferritin, total iron binding capacity, serum potassium, serum calcium, serum phosphorus, parathyroid hormone, urea nitrogen, albumin, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol between two groups ( P>0.05). There was statistical difference in erythrocyte aggregation between two groups ( P<0.05); there were no statistical differences in the number of vascular loops, diameter of input branch, diameter of output branch, length of loop, diameter of loop top, blood flow rate, clarity, condition of cross loop, condition of malformed loop, shape of nipple and subpapillary venous plexus between two groups ( P>0.05). The morphology integral and total integral in cardiovascular events group were significantly higher than those in non-cardiovascular events group: 1.8 (1.1, 3.1) scores vs. 1.4 (0.8, 2.5) scores and 4.2 (2.4, 6.1) scores vs. 3.1 (1.8, 5.2) scores, and there were statistical differences ( P<0.05); there were no statistical differences in flow integral and loop integral between two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of the total integral of nail fold microcirculation for predicting cardiovascular events in hemodialysis patients was 0.590 (95% CI 0.506 to 0.673), the best cut-off value was 2.85 scores, the sensitivity was 69.7% and the specificity was 45.9%. Conclusions:The nail fold microcirculation disorder is more serious in hemodialysis patients with cardiovascular events. The nail fold microcirculation detection may help to predict cardiovascular disease.

Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.

Objective:To screen plasma metabolic markers in patients with unexplained recurrent spontaneous abortion (URSA) by non-target metabolomics approach.Methods:From September 2022 to May 2023, the plasma of 23 URSA pregnant women with threatened abortion who visited the outpatient clinic of Gansu Provincial Maternity and Child-care Hospital in the first trimester (URSA group) was collected, and the plasma of 22 healthy pregnant women in the first trimester who underwent prenatal examination during the same period (normal control group) was collected. Plasma metabolomics was analyzed by ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS), fold change analysis, principal component analysis and partial least square discriminant analysis were applied to screen for differential metabolites, and the metabolites and their pathways associated with URSA were screened using receiver operating characteristic (ROC) curve and pathway enrichment analysis.Results:There were no significant differences in age, body mass index and gestational weeks between URSA and normal control group(all P<0.05). Metabolomics analysis using UPLC-MS showed that a total of 526 metabolites were detected from plasma, of which 33 were found to be differential metabolites associated with URSA based on the screening standards. Six potential metabolites with large area under the curve (AUC) were identified by ROC curve analysis, including phosphatidylethanolamine (AUC=0.972, 95% CI: 0.920-1.000), santene hydrate (AUC=0.902, 95% CI: 0.786-0.982), L-leucine (AUC=0.884, 95% CI: 0.772-0.960), cembrene (AUC=0.881, 95% CI: 0.758-0.956), caffeine (AUC=0.875, 95% CI: 0.756-0.962), and 4-hydroxybenzoic acid propyl ester (AUC=0.864, 95% CI: 0.732-0.946). The AUC for the combined diagnosis of URSA by the six metabolites was 0.983 (95% CI: 0.929-1.000). Pathway enrichment analysis of the differential metabolites showed that the pathogenesis of URSA was associated with a variety of metabolic pathways including caffeine metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. Conclusion:The plasma metabolic profiles of pregnant women with normal pregnancies versus URSA differ in early pregnancy, and six potential metabolites such as phosphatidylethanolamine, santene hydrate, L-leucine, cembrene, caffeine, 4-hydroxybenzoic acid propyl ester, and their metabolic pathways may be involved in the pathogenesis of URSA.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .

Objective To evaluate and summarize the evidence related to the prevention of parenteral nutritional support complications in inpatients,and to provide an evidence-based basis for guiding healthcare professionals to prevent parenteral nutritional support complications in a scientific and standardized manner.Methods Computerized search was conducted in UpToDate,BMJ Best Clinical Practice,Centre for Evidence-Based Health Care database of the Joanna Briggs Institute in Australia,Ontario Registered Nurses Association website in Canada,National Institute for Health and Clinical Excellence website in the United Kingdom,Scottish Intercollegiate Guidelines Network,Guidelines International,New Zealand Guidelines Collaborative,American Society for Parenteral and Enteral Nutrition website,European Society for Clinical Nutrition and Metabolism Society website,International Practice Guidelines Registry Platform China Clinical Guidelines Repository,Medical Pulse,PubMed,Cochrane Library,Web of Science,CINAHL,Embase,China Biomedical Literature Database,CNKI,Wanfang Database,etc.The search period was from the time of database construction to October 2023.After literature screening and quality evaluation,the evidence extraction and integration were carried out.Results A total of 16 papers were included,including 3 clinical decision-making,1 evidence summary,4 guidelines,6 expert consensuses,and 2 systematic evaluations.27 pieces of best evidence were extracted from 3 areas,namely metabolic complications,mechanical complications,and infectious complications.Conclusion This study summarized the evidence related to the prevention and management of complications of parenteral nutrition support in adult inpatients,aiming to provide an evidence-based basis for healthcare professionals to develop scientific and standardized measures for the prevention and management of complications of parenteral nutrition support.

Objective To construct a nomogram risk prediction model for symptomatic cerebrovas-cular ischaemia based on intra-plaque neovascularisation in carotid arteries in patients with ische-mic cerebrovascular disease(ICVD).Methods A retrospective study was conducted on 320 ICVD patients who were consecutively admitted to Wuhan Fourth Hospital from April 2020 to April 2024.In a ratio of 3∶1,240 cases were assigned into a training set and 80 cases into a validation set.The patients in the training set were further divided into 147 cases in the symptomatic sub-group and 93 cases in the asymptomatic subgroup according to the presence or absence of relevant symptoms or signs.Multifactorial logistic regression analysis was used to identify the risk factors for symptomatic ischemia in ICVD patients,and a nomogram risk prediction model was construc-ted and the prediction efficacy of the model was evaluated.Results The proportions of plaque multiplicity,ulcerated plaque,stenosis ≥70％,and intra-plaque neovascularization were signifi-cantly higher in the symptomatic subgroup than the asymptomatic subgroup(P＜0.05,P＜0.01).Multifactorial logistic regression analysis showed that plaque multiplicity(OR=1.261,95％CI:1.088-1.539,P=0.003),ulcerated plaque(OR=1.458,95％CI:1.132-1.661,P=0.001),and stenosis ≥70％(OR=2.023,95％CI:1.458-2.561,P=0.001),and intra-plaque neovasculariza-tion(OR=1.206,95％CI:1.057-1.489,P=0.002)were independent risk factors for the occur-rence of symptomatic cerebral ischemia in ICVD patients.H-L deviation test showed that the con-structed nomogram risk prediction model had a good fit(x2=9.362,P=0.295).Internal and ex-ternal validation showed that the calibration curves for both the training and validation sets were consistent with the original curves,and the AUC value was were 0.871 and 0.864,respectively.De-cision curve analysis showed that the model had a significant standardized clinical net benefit when the predicted risk threshold exceeded 0.01.Conclusion Ultrasonography is instructive in as-sessment of the presence or absence of intra-plaque neovascularization in carotid atherosclerotic plaques.And our constructed nomogram risk prediction model has good predictive value for the development of symptomatic cerebral ischemia.

Objective To explore the effect of controlled low central venous pressure(CLCVP)on venous congestion and postoperative acute kidney injury(AKI)in cardiac surgery under cardiopulmonary bypass(CPB).Methods A total of 137 patients scheduled for elective cardiac surgery under general anes-thesia with CPB were selected,including 73 males and 64 females,aged 18 to 70 years,with a BMI of 20 to 28 kg/m2,and ASA physical status Ⅱ or Ⅲ.The patients were randomly assigned into two groups:the controlled low central venous pressure group(group CL,n=68)and the control group(group C,n=69).In group CL,CLCVP was applied by pumping nitroglycerin to reduce CVP to below 10 mmHg after 20 minutes of CPB cessation until the end of surgery.If necessary,norepinephrine was applied to maintain MAP≥65 mmHg.Patients in group C received standardized anesthesia management.Urine samples were collected before anesthesia induction and 12 hours postoperatively to detect the concentration of kidney injury molecule-1(KIM-1).Urine samples were also collected before anesthesia induction and 2 hours postopera-tively to detect the concentration of neutrophil gelatinase-associated lipocalin(NGAL).Cumulative time a-bove 10,12,16,and 20 mmHg and time-weighted average CVP were used to assess venous congestion.The occurrence of postoperative AKI,stage 2 or above AKI,renal replacement therapy(CRRT),postoperative low cardiac output syndrome(LCOS),acute kidney injury following cardiac surgery(AKICS)score when arriving in ICU,in-hospital mortality,ICU stay,and postoperative hospital stay were recorded.Results Compared with group C,the cumulative time of CVP above 10,12,16,and 20 mmHg after CPB in group CL was significantly shorter,and the time-weighted average CVP was significantly lower(P＜0.05).AKI occurred in 9 patients(13.2%)in group CL and 15 patients(21.7%)in group C postoperatively,and there was no significant difference between the two groups.One case(1.5%)of stage 2 or above AKI oc-curred in group CL and 2 patients(2.9%)in group C,with one patient in group C requiring CRRT.Com-pared with group C,the concentrations of KIM-1 at 12 hours postoperatively and NGAL at 2 hours postoper-atively were significantly lower in group CL(P＜0.05).There were no statistically significant differences between the two groups in LCOS,AKICS score,in-hospital mortality,ICU stay,and postoperative hospital stay.Conclusion Controlled low central venous pressure in cardiac surgery under cardiopulmonary bypass can reduce venous congestion and decrease the occurrence of postoperative renal injury,thereby exerting a certain renal protective effect.

Objective:To investigate the expression level and application value of anti-carbamylated protein(CarP)antibody in rheumatoid arthritis(RA).Methods:Demographic data and laboratory test results of RA patients,non-RA patients and healthy controls in the physical examination center were re-viewed from December 2018 to June 2019 in the Rheumatology and Immunology Department of the Peo-ple's Hospital of Xinjiang Uygur Autonomous Region.The serum concentrations of anti-CarP antibodies in all the subjects were measured by ELISA and statistically analyzed.Results:A total of 259 subjects were included in this study,including 158 in the RA group(45 serum-negative RA patients),59 in the non-RA group and 42 in the healthy control group.The concentration of anti-CarP antibody in RA group[8.31(5.22,15.26)U/mL]was higher than that in non-RA group[4.50(3.35,5.89)U/mL]and healthy control group[3.46(2.76,4.92)U/mL].The concentration of anti-CarP antibody in non-RA group was not significantly different from that in healthy control group(P=0.10).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of anti-CarP antibody in the diagnosis of RA was 58.2％,and the specificity was 93.1％.The sensitivity of the combined detection of anti-CarP antibody,anti-cyclic peptide containing citrulline(CCP)antibody and rheumatoid factor(RF)was 82.3％,and the specificity was 96.5％.The positive rate of anti-CarP antibody in serum-negative RA patients was 44.4％(20/45).Univariate Logisitic regression analysis showed that age,C-reactive pro-tein(CRP),erythrocyte sedimentation rate(ESR),RF,glucose-6-phosphate isomerase(GPI),anti-CCP antibody and anti-CarP antibody were risk factors for RA.Multivariate Logisitic regression analysis showed that anti-CCP antibody and anti-CarP antibody were independent risk factors for RA.Spearman correlation analysis showed that there was no significant correlation between anti-CarP antibody and swol-len joint count(SJC),tenderness joints count(TJC),ESR,disease activity score for 28 joints(DAS28),clinical disease activity index(CDAI),simplified disease activity index(SDAI).The concentration of anti-CarP antibody in RA with bone erosion(n=88)was higher than that in RA without bone erosion(n=70),and there was significant difference between the two groups(P＜0.05).Conclusion:Anti-CarP antibody is an effective serological marker for the diagnosis of RA.The combined detection of RF,anti-CCP antibody and anti-CarP antibody can improve its diagnostic value,and anti-CarP antibody may be an effective assistant diagnostic tool for serum negative RA.The high serum concentration of anti-CarP antibody in patients with RA may indicate an increased risk of bone erosion and should be treated early,but further cohort studies are needed for follow-up observation.