SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity / 药物分析学报

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Effectiveness and security of anisodine hydrobromide tablets in treating nonarteritic anterior ischemic optic neuropathy: a Chinese multicenter nonrandomized controlled study / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Comparison of clinical characteristics and outcomes of infants with moderate and severe acute respiratory distress syndrome diagnosed according to baseline oxygenation index / 中国小儿急救医学

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

The value of bedside ultrasound and biomarkers in the diagnosis of sepsis-induced myocardial dysfunction and prognosis of septic shock in children / 中国小儿急救医学

Objective:To evaluate the feasibility of using bedside ultrasound and serum biomarkers for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic shock patients.Methods:The patients diagnosed as septic shock were enrolled in the study from January 2019 to July 2021 in PICU at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Bedside ultrasound results were recorded at day 1, 2, 3, 7 and 10.Blood samples were collected at the same time, markers of myocardial injury were detected, and prognosis was recorded at 28 days.According to the left ventricular ejection fraction (LVEF), children with septic shock were divided into SIMD group and non-SIMD group.Those with LVEF <50% or decreased by ≥10% from baseline level were defined as SIMD.Differences in cardiac ultrasound parameters and biomarkers between two groups were compared.Logistic regression analysis was performed to determine the independent risk factors for SIMD and the independent risk factors for death at 28 days after septic shock.The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different indicators in predicting SIMD and the death outcome of children with septic shock on 28 days.Results:A total of 57 children were enrolled, including 28 cases in SIMD group and 29 cases in non-SIMD group.Univariate analysis showed that there were statistically significant differences in pediatric critical illness score, N-terminal B-type natriuretic peptide(NT-proBNP), LVEF and left ventricular short axis shortening rate between two groups ( P<0.05). Logistic analysis demonstrated that LVEF( OR=0.890, 95% CI 0.818-0.969, P=0.007)and NT-proBNP ( OR=1.000, 95% CI 1.000-1.000, P=0.015)could independently predict SIMD.There were 42 cases in survival group and 15 in non-survival group according to the prognosis on 28 days.Univariate analysis showed that there were significant differences in pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I, and mitral annular plane systolic excursion(MAPSE)( P<0.05). Logistic analysis showed that only MAPSE independently predicted mortality( OR=85.670, 95% CI 1.685-4 356.736, P=0.026). Compared with MAPSE(AUC=0.727), MAPSE combined with pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I(AUC=0.926) could be better to predict the 28 days prognosis of patients with septic shock on 28 days. Conclusion:NT-proBNP increases significantly in the early stage of SIMD.MAPSE shows no difference between SIMD and non-SIMD patients.MAPSE is correlated with the prognosis of patient with septic shock.

Gut microbiota and neonatal necrotizing enterocolitis / 中国小儿急救医学

The pathophysiology of neonatal necrotizing enterocolitis (NEC) is not clear, but is considered to be multifactorial.Immaturity of the gut, hypoxia-ischemia, formula feeding and microbial dysbiosis play roles in inducing intestinal inflammatory response.This review discussed the development process of infant gut microbiota, the factors affecting neonatal intestinal colonization, the roles of gut microbiome in the pathogenesis of NEC, and the manifestations of early microecology disorder in NEC.In addition, studies on the use of probiotics to prevent NEC and the risks of using probiotics in preterm infants were also summarized.

Construction of sensitive index system of nursing quality in patients with acute ischemic stroke patients undergoing interventional thrombectomy / 中国实用护理杂志

Objective:To construct a sensitive index system of nursing quality for patients with acute ischemic stroke patients undergoing interventional thrombectomy, so as to provide a scientific basis for interventional thrombectomy care for acute ischemic stroke.Methods:Taking the "structure-process-result" three-dimensional quality model as the theoretical framework, through evidence-based literature search, the item pool was drawn up, and finally the indicators and their weights at each level were determined by two rounds of Delphi method in December 2021 and January 2022 and analytic hierarchy process.Results:The positive coefficients of the two rounds of inquiries to experts were 0.92 and 1.00, respectively, the authority coefficients were 0.913 and 0.917, and the Kendall coefficients were 0.141 and 0.202, respectively. The final index system consisted of 3 primary indicators, 9 secondary indicators and 50 three-level indicators.Conclusions:The nursing sensitive quality index system for patients with acute stroke patients undergoing interventional thrombectomy constructed in this study has high reliability and scientificity, which can provide target incentives for clinical nurses and provide reference for the development of specialized nursing sensitive quality indicators.

Construction and application of neonatal asphyxia risk prediction model in cesarean section / 中国实用护理杂志

Objective:To establish a risk prediction model for neonatal asphyxia in cesarean section and test its application effect.Methods:This was a retrospective study. We retrospectively analyzed the clinical data of 2 244 infants (modeling group) who were delivered by cesarean section in Affiliated Hospital of Weifang Medical University from April 2021 to December 2021. Newborns were divided into asphyxia group ( n=176) and non-asphyxia group ( n=2 068) according to the occurrence of neonatal asphyxia. Logistic regression was used to screen the risk factors of neonatal asphyxia in cesarean section and a line chart model was established to predict the risk. Another 683 neonates were selected as validation group for external validation of the model from January to March in 2022. Results:Five factors including preterm birth, fetal distress, fetal growth restriction, abnormal S/D value of umbilical artery and umbilical cord around the neck were included in the prediction model. The area under ROC curve of the modeling group was 0.902, the Youden index was 0.687, the sensitivity was 0.837, and the specificity was 0.850. Hosmer-lemeshow test showed that χ2=1.79, and P=0.877. In the validation group, the area under ROC curve was 0.823, the Youden index was 0.555, the sensitivity was 0.835, and the specificity was 0.720. It showed that the model had a good fitting effect and identification validity. Conclusions:The risk prediction model has a good clinical application value in the prediction of neonatal asphyxia in cesarean section, and provides reference for obstetricians to take preventive management measures of neonatal asphyxia in time.

The role of Huaiqihuang Granules in the long-term management of bronchial asthma in young children: a multicenter real-world study / 中华实用儿科临床杂志

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Newest etiology of infantile spasms syndrome / 中华实用儿科临床杂志

Infantile spasms syndrome (ISs) is a kind of catastrophic epileptic encephalopathy.Epileptic spasms originating in infancy or early childhood, typically accompanied by an electroencephalographic pattern of hypsarrhythmia, and developmental regression are common clinical manifestations.ISs prognosis is primarily determined by its etiology.In recent years, the rapid development of neuroimaging and genetic detection technology has greatly enriched the etiological spectrum of ISs, especially the genetic-related etiology.Likewise, the etiological categorization of ISs has gotten increasingly specific in response to clinical demands.Despite these advances, the etiology of ISs remains complicated and variable, with around one-third of children having unidentified causes.Consequently, more detection methods and studies are still needed to identify other potential etiologies.The etiologic categorization of ISs will be evaluated in this article.

Asymptomatic cerebral artery stenosis and cognitive impairment / 国际脑血管病杂志

Asymptomatic cerebral artery stenosis (aCAS) is closely associated with cognitive impairment, which can lead to multiple cognitive domain impairments, thereby affecting the behavior and daily life of patients. This article reviews the main involved cognitive domains, injury mechanisms, and treatment in different types of aCAS, with the aim of increasing attention to aCAS, early clinical intervention, and delaying cognitive deterioration.

Clinical observation of venetoclax-based treatment regimens for acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

Progress of minimal residual disease monitoring in adult acute lymphoblastic leukemia / 白血病·淋巴瘤

Acute lymphoblastic leukemia (ALL) is a malignancy originating from B-/T-lineage lymphoid progenitor cells. With the continuous development of new drugs as well as therapeutic regimens, adult ALL patients have improved complete remission rates and overall survival rates, but the survival rate of patients after relapse remains low. The positive minimal residual disease after complete remission is an important reason for relapse. Although minimal residual disease monitoring has been found to be important in predicting patients prognosis in recent years, the uniform stratified treatment protocols have not yet been developed in the clinical practice of adult ALL. This article reviews the prognostic significance of minimal residual disease monitoring at different time points, as well as the progress of removal methods of minimal residual disease.

Development of a portable radiation detector for nuclide identification based on CdZnTe / 中国辐射卫生

Objective To develop a portable nuclear radiation detector with low-energy γ-nuclide recognition capability for rapid measurement of the dose levels in low-energy radiation fields and identification of nuclides. Methods A digital multi-channel circuit was developed for a detector based on the room temperature semiconductor cadmium zinc telluride, nuclide recognition was achieved using an intelligent nuclide recognition algorithm, and the energy response function G(E) was used to calculate the real-time ambient dose equivalent rate H*(10). Results The portable spectrometer had a minimum detectable energy of 20 keV, and the typical energy resolution for low-energy X-rays was > 4.10% at 59.5 keV and 20℃, enabling accurate identification of 241Am nuclide. Conclusion The device has a good measurement performance for low-energy γ/X rays, effectively addressing the limitations of existing devices for monitoring low-energy radiation fields, and provide reliable technical methods for monitoring and emergency response in spent fuel reprocessing plants or nuclear material production plants.

Stress Distributions Affected by Different Filling Blocks in Medial Opening Wedge High Tibial Osteotomy / 医用生物力学

Objective To analyze the influence from material and size of the filling block on stress distributions of the tibial osteotomy model. Methods The filling blocks with three different materials (iliac bone, cancellous bone and polyetheretherketone (PEEK)) and five different sizes were established and implanted to the tibial osteotomy models, respectively. The mechanical loads were applied on the model, the stress distribution and edge displacement of the model were analyzed. Results For three kinds of materials, the stress at proximal end of the tibia and the plate, as well as edge displacement in the model implanted with filling block by iliac bone material were lower than those of the cancellous bone and PEEK, but the filling block by iliac bone material had the highest stress. When the filling blocks with different sizes were implanted in osteotomy space, the stress distribution on each part of the tibial osteotomy and edge displacement were different. Especially when the width of the filling block was reduced from 30 mm to 10 mm, the peak stress of the proximal tibia, steel plate and filling block was increased by 49. 3% , 92. 7% and 54. 4% on average. Conclusions Different filling block parameters will affect the stress distribution in different parts of the tibial osteotomy. The research results provide the theoretical basis for parameter selection of the tibial osteotomy filling block in clinic.

Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To evaluate the regulatory effect of berberine on autophagy and apoptosis balance of fibroblast-like synoviocytes (FLSs) from patients with in rheumatoid arthritis (RA) and explore the mechanism.@*METHODS@#The inhibitory effect of 10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine on RA-FLS proliferation was assessed using CCK-8 method. Annexin V/PI and JC-1 immunofluorescence staining was used to analyze the effect of berberine (30 μmol/L) on apoptosis of 25 ng/mL TNF-α- induced RA-FLSs, and Western blotting was performed to detect the changes in the expression levels of autophagy- and apoptosis-related proteins. The cells were further treated with the autophagy inducer RAPA and the autophagy inhibitor chloroquine to observe the changes in autophagic flow by laser confocal detection of mCherry-EGFP-LC3B. RA-FLSs were treated with the reactive oxygen species (ROS) mimic H2O2 or the ROS inhibitor NAC, and the effects of berberine on ROS, mTOR and p-mTOR levels were observed.@*RESULTS@#The results of CCK-8 assay showed that berberine significantly inhibited the proliferation of RA-FLSs in a time- and concentration-dependent manner. Flow cytometry and JC-1 staining showed that berberine (30 μmol/L) significantly increased apoptosis rate (P < 0.01) and reduced the mitochondrial membrane potential of RA-FLSs (P < 0.05). Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01) and increased the expression of p62 protein in the cells (P < 0.05). Detection of mCherry-EGFP-LC3B autophagy flow revealed obvious autophagy flow block in berberine-treated RA-FLSs. Berberine significantly reduced the level of ROS in TNF-α-induced RA-FLSs and upregulated the expression level of autophagy-related protein p-mTOR (P < 0.01); this effect was regulated by ROS level, and the combined use of RAPA significantly reduced the pro-apoptotic effect of berberine in RA-FLSs (P < 0.01).@*CONCLUSION@#Berberine can inhibit autophagy and promote apoptosis of RA-FLSs by regulating the ROS-mTOR pathway.

Preliminary application of combined auditory monitoring technique in resection of vestibular neurinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the value of electrically evoked auditory brainstem response (EABR) monitoring combined with brainstem auditory evoked potential (BAEP) and compound action potential (CAP) monitoring during vestibular schwannoma resection for the protection of the cochlear nerve. Methods: Clinical data from 12 patients with vestibular schwannomas who had useful hearing prior to surgery were analyzed at the PLA General Hospital from January to December 2021. Among them, there were 7 males and 5 females, ranging in age from 25 to 59 years. Before surgery, patients underwent audiology assessments (including pure tone audiometry, speech recognition rate, etc.), facial nerve function evaluation, and cranial MRI. They then underwent vestibular schwannoma resection via the retrosigmoid approach. EABR, BAEP, and CAP were simultaneously monitored during surgery, and patients' hearing preservation was observed and analyzed after surgery. Results: Prior to surgery, the average PTA threshold of the 12 patients ranged from11 to 49 dBHL, with a SDS of 80% to 100%. Six patients had grade A hearing, and six patients had grade B hearing. All 12 patients had House-Brackman grade I facial nerve function prior to surgery. The MRI indicated tumor diameters between 1.1 and 2.4 cm. Complete removal was achieved in 10/12 patients, while near-total removal was achieved in 2/12 patients. There were no serious complications at the one-month follow-up after surgery. At the three-month follow-up, all 12 patients had House-Brackman grade I or II facial nerve function. Under EABR with CAP and BAEP monitoring, successful preservation of the cochlear nerve was achieved in six of ten patients (2 with grade B hearing, 3 with grade C hearing, and 1 with grade D hearing). Successful preservation of the cochlear nerve was not achieved in another four patients (all with grade D hearing). In two patients, EABR monitoring was unsuccessful due to interference signals; however, Grade C or higher hearing was successfully preserved under BAEP and CAP monitoring. Conclusion: The application of EABR monitoring combined with BAEP and CAP monitoring during vestibular schwannoma resection can help improve postoperative preservation of the cochlear nerve and hearing.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Spatial correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in a typical coal-fired pollution fluorosis area / 中华流行病学杂志

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.