Objective To investigate the effect of hemoglobin A1c variability on the incidence of malignant tumors in type 2 diabetes mellitus (T2DM) patients, and to provide a reference for the prevention and treatment of diabetes. Methods A retrospective cohort study was used to integrate Shanghai malignant tumor registration information and T2DM patient management information of Minhang Districts in Shanghai. A record linkage was carried out using ID numbers for patients who had been diagnosed through the Cancer Registry System. Average Real Variability（ARV）was used to assess the variability for hemoglobin A1c results, with no less than 3 measurements and no more than 1 follow-up visit per year. Cox proportional hazards regression models and Restricted Cubic Splines (RCS) were used for statistical analysis. ARV was grouped using quartile classification, represented by Q1, Q2, Q3, and Q4, respectively. Cox regression was performed using unadjusted model I and model II adjusted for gender, age, and group. Results A total of 2 762 research subjects were included in the present study, with 45.84% males and 54.16% females. The average age was (63.58±10.11) years, and an average follow-up time was (9.96±3.66) years. Malignant tumor incidence rate was 345.45/100 000 person years. There was statistical significance among different ARV groups (P=0.01). COX regression analysis of model I and model II showed that compared with Q1, the risk of Q4 group was significantly increased, with HRs of 2.72 (1.56-4.74) and 2.68 (1.53-4.68), respectively. The RCS graph's analysis showed that except for the ≥65-year-old group, the risk of tumor incidence gradually increased with the increase of ARV coefficient. Conclusion The variability of hemoglobin A1c is positively associated with the risk of occurrence of malignant tumors in type 2 diabetes patients. It is necessary to strengthen the monitoring of hemoglobin A1c and to reduce the health hazards caused by fluctuations in hemoglobin A1c.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors. With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity (CTR-CVT) in tumor patients, noninvasive imaging technologies play pivotal roles in the risk stratification, early diagnosis, monitoring and follow-up for CTR-CVT. In recent years, the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies, with several pertinent guidelines and expert consensus documents issued in China and abroad. However, there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology. Therefore, the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology, the Ultrasound Branch of the Chinese Medical Association, and the Chinese Society of Echocardiography convened experts to formulate the "Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity". Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad, and in conjunction with data derived from evidence-based medical research in China, this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT, aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.

Objective To investigate the predictive value of pan-immune inflammatory values(PIV)in the prognosis of patients with ischemic stroke(AIS)treated with intravascular intervention combined with tirofiban.Methods 102 AIS cases admitted to the Department of Neurology of the First People's Hospital of Zhaotong from January 2019 to December 2023 and treated with intravascular intervention combined with Tirofiban were selected as the study objects.The patients were divided into the mild group(n=9),moderate group(n=45)and severe group(n=48)according to the score of NIHSS after the admission.According to the mRS 90 days after the treatment,the cases were divided into the good prognosis group(n=63)and poor prognosis group(n=38).Data were collected and analyzed.The predictive value of PIV level in patients with ischemic stroke treated with intravascular intervention combined with tirofiban was evaluated by ROC.The risk factors of adverse outcomes in patients with ischemic stroke treated with intravascular intervention combined with tirofiban were investigated by multivariate Logistic regression.Results A total of 102 patients with ischemic stroke were included.The PIV level in the good prognosis group 331.1(221.9,662.7)was lower than that in the poor prognosis group 1 025.7(451.5,1 841.3)(P<0.05).PIV level in the severe group was higher than that in the mild and moderate groups,and PIV level in the moderate group was higher than that in the mild group(P<0.05).The AUC(95％CI)of PIV for predicting adverse outcomes of intravascular intervention combined with tirofiban in patients with ischemic stroke was 0.750(95％CI 0.654～0.831),the cut-off point was 834.92,the specificity was 85.71％and the sensitivity was 65.79％.NIHSS score>18(OR=5.944 95％CI 2.011～19.137),PIV>834.92(OR=4.863,95％CI 1.410～18.685)were the risk factors for the poor outcome of intravascular intervention combined with tirofiban in patients with ischemic stroke(P<0.05).Conclusion Elevated PIV is closely related to the poor outcomes in patients with ischemic stroke treated with intravascular intervention combined with Tirofiban.High PIV and NIHSS scores are both risk factors for the poor prognosis in patients with ischemic stroke,and can be used as the sensitive indicators for the early identification.

Objective·To analyze the epidemiological characteristics of risk factors for cardiovascular diseases and malignant tumors based on the Shanghai community elderly cohort.Methods·The study subjects were selected from the Shanghai community elderly cohort established from February to August 2019,with a total of 17 948 people.The study subjects were divided into 4 groups according to self-reported presence or absence of tumors and/or cardiovascular diseases during the baseline survey:tumor-free and non-cardiovascular disease group,single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group.The differences among the four groups of subjects were collected and compared in terms of demographic characteristics and physiological indicators,daily living habits(smoking,drinking tea,drinking coffee,drinking carbonated drink,drinking alcohol,sedentary time,physical activity level and sleep quality),past medical history,psychological status(depression and anxiety)and dietary compliance.Results·Among the study subjects,60.1%of tumor patients were complicated with cardiovascular diseases.The differences among the four groups of subjects in age,gender,educational level,pre-retirement occupation,waist circumference,hip circumference and body mass index were statistically significant(all P<0.05).Compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group all exhibited lower proportions of smoking and high physical activity levels(all P<0.05),and higher proportion of sedentary time exceeding 4 h/d and poor sleep quality(all P<0.05);the proportion of subjects with past medical histories including hyperlipidemia,peripheral vascular disease,endocrine system disease,respiratory system disease,urinary system disease and digestive system disease of the single cardiovascular disease group and the tumor cardiovascular disease co-occurrence group was higher(all P<0.05),and the proportion of subjects with depression and anxiety was also higher(all P<0.05).Furthermore,compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group had lower compliance rates of poultry,fish,fruit and liquid milk(all P<0.05).Among the four groups,only the compliance rate of vegetable intake exceeded 50%,while the compliance rates of poultry,fish,fruit,liquid milk and tubers were all below 20%.Conclusion·In the elderly population of Shanghai communities,over half of malignant tumor patients are concomitant with cardiovascular diseases.Unhealthy daily habits are prevalent among those with cardiovascular diseases,tumors and tumor-cardiovascular disease co-occurrence.The intake of many foods in the elderly of the community do not reach the levels recommended by Chinese Dietary Guidelines.

Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy,using common laboratory and transthoracic echocardiography indices.Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,between September 2020 and September 2022,were included.General patient information,laboratory test results,and transthoracic echocardiography data were collected.After feature extraction,five machine learning algorithms,including random forest(RF),gradient boosting(GB),support vector machine(SVM),K-nearest neighbor(KNN),and decision tree(DT),were applied to construct a prediction model for the changes of the patients' metabolic state after neoadjuvant therapy,and the prediction performances of the five models were compared.Results·A total of 232 cases with valid clinical data were included,comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy.Feature extraction identified five key features:white blood cell count,hemoglobin,high-density lipoprotein(HDL),interleukin-2 receptor,and interleukin-8.In the multi-feature analysis,the area under the receiver operating characferistic curve(AUC)was higher in the combination of white blood cell count,hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8(RF:0.928 vs 0.772,GB:0.900 vs 0.792,SVM:0.941 vs 0.764,KNN:0.907 vs 0.762,DT:0.799 vs 0.714).The RF,SVM,and GB models showed higher AUC(0.928,0.941,0.900)and accuracy(0.914,0.897,0.776).The SVM model exhibited superior accuracy in the training data compared to the RF and GB models(P=0.394,0.122 and 0.097,respectively).Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators,namely,white blood cell count,hemoglobin,high-density lipoprotein,interleukin-2 receptor,and interleukin-8.SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient's inflammatory metabolic state.