Research progress on roles and mechanisms of DNA hydroxymethylation in health effects induced by arsenic exposure / 环境与职业医学

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

Burden of epilepsy in China and its provinces, 1990 to 2019: findings from the Global Burden of Disease Study 2019 / 中华医学杂志(英文版)

BACKGROUND@#Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces.@*METHODS@#We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019.@*RESULTS@#In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92-1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33-133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03-98.74%) and 35.72% (95% UI: 0.47-86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43-5.66]/100,000), Qinghai (1.80 [95% UI: 1.15-2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88-1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39-0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44-0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41-0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased.@*CONCLUSIONS@#The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.

Efficacy of Bevacizumab Combined with Paclitaxel and Platinum-Based Chemotherapy in Advanced Metastatic Cervical Cancer and Its Effect on T Lymphocyte Subsets and Tumor Markers / 肿瘤防治研究

Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.

Construction and management model practice of a patient-derived xenograft model platform / 中华医学科研管理杂志

Objective:In the era of precision medicine, there is an urgent need for a preclinical evaluation method with a high cost-benefit ratio to improve the effectiveness and value of clinical trials.Methods:Taking clinical needs and scientific research purposes as the starting point, the platform focused on four aspects of project management, information retrieval, quality control, and practical application, and introduced in detail the management practice of building a patient-derived xenograft model platform system.Results:With the support of the institutional system, quality control system, and information system, the patient-derived xenograft model platform was formed with standardization as the core. With the assistance of this platform and scientific research management, as of December 2021, there are 48 animal models of patient-derived xenograft in the database. In total of 6 SCI scientific and technological articles were published using these animal models, with a total impact factor of 36.77 (the highest single article was 7.333). In total of 6 direct industrial projects, 6 clinical trial-related projects, and 4 NSFC projects were approved with a total research fund of 1.5 million yuan.Conclusions:Continuous construction and improvement of the existing platform will help promote the development of basic research translation and clinical research in the field of oncology, and accelerate the development of new oncological diagnosis and treatment models, thereby benefiting more patients.

Study on predicting the risk of retinal vein occlusion based on nomogram model and systemic risk factors / 中华眼底病杂志

Objective:To establish and preliminarily validate a nomogram model for predicting the risk of retinal vein occlusion (RVO).Methods:A retrospective clinical study. A total of 162 patients with RVO (RVO group) diagnosed by ophthalmology examination in The Second Affiliated Hospital of Xi'an Jiaotong University from January 2017 to April 2022 and 162 patients with age-related cataract (nRVO group) were selected as the modeling set. A total of 45 patients with branch RVO, 45 patients with central RVO and 45 patients with age-related cataract admitted to Xi'an Fourth Hospital from January 2022 to February 2023 were used as the validation set. There was no significant difference in gender composition ratio ( χ2=2.433) and age ( Z=1.006) between RVO group and nRVO group ( P=0.120, 0.320). Age, gender, blood routine (white blood cell count, hemoglobin concentration, platelet count, neutrophil count, monocyte count, lymphocyte count, erythrocyte volume, mean platelet volume, platelet volume distribution width), and four items of thrombin (prothrombin time, activated partial thrombin time, fibrinogen, and thrombin time) were collected in detail ), uric acid, blood lipids (total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, lipoprotein a), hypertension, diabetes mellitus, coronary heart disease, and cerebral infarction. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were calculated. The single logistic regression was used to analyze the clinical parameters of the two groups of patients in the modeling set, and the stepwise regression method was used to screen the variables, and the column graph for predicting the risk of RVO was constructed. The Bootstrap method was used to repeated sample 1 000 times for internal and external verification. The H-L goodness-of-fit test and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discrimination of the nomogram model. Results:After univariate logistic regression and stepwise regression analysis, high density lipoprotein, neutrophil count and hypertension were included in the final prediction model to construct the nomogram. The χ2 values of the H-L goodness-of-fit test of the modeling set and the validation set were 0.711 and 4.230, respectively, and the P values were 0.701 and 0.121, respectively, indicating that the nomogram model had good prediction accuracy. The area under the ROC curve of the nomogram model for predicting the occurrence of post-stroke depression in the modeling set and the verification set was 0.741 [95% confidence interval ( CI) 0.688-0.795] and 0.741 (95% CI 0.646-0.836), suggesting that the nomogram model had a good discrimination. Conclusions:Low high density lipoprotein level, high neutrophil count and hypertension are independent risk factors for RVO. The nomogram model established based on the above risk factors can effectively assess and quantify the risk of post-stroke depression in patients with cerebral infarction.

Family report of Wolf-Hirschhorn syndrome in twins / 中华神经科杂志

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

Efficacy and safety of thrombolytic therapy with intravenous alteplase in elderly patients with acute cerebral infarction on maintenance dialysis / 中华老年医学杂志

Objective:To investigate the efficacy and safety of thrombolytic therapy with intravenous alteplase(rt-PA)for elderly acute ischemic stroke patients on maintenance hemodialysis.Methods:In this retrospective study, data of 165 elderly patients with acute cerebral infarction on maintenance dialysis, aged 65-85, treated at the Stroke Center of the Fourth Central Hospital Affiliated to Nankai University between May 2018 and March 2021, were collected.Based on whether intravenous thrombolysis with alteplase(rt-PA)was used and differences in thrombolytic schemes, patients were divided into a conservative treatment group( n=58, receiving only standardized secondary stroke prevention), a low-dose rt-PA group( n=57, receiving rt-PA intravenous thrombolysis, 0.6 mg/kg)and a standard-dose rt-PA group( n=50, receiving rt-PA intravenous thrombolysis, 0.9 mg/kg). The safety and efficacy of rt-PA treatment were assessed. Results:The rate of effectiveness at 24 h and the rate of good prognosis at 7 d were 64.9%(37/57)and 70.2%(40/57)for the low-dose rt-PA group and 68.0%(34/50)and 74.0%(37/50)for the standard dose group, respectively.There was no significant difference between the two groups( χ2=0.417, P=0.518; χ2=0.636, P=0.425), but these rates were better than 29.3%(17/58)and 41.4%(24/58)for the conservative treatment group( χ2=10.583、16.714, P<0.001). The good prognosis rate at 90 days were 73.7%(42/57), 78.0%(39/50)and 69.0%(40/58)for the three groups, respectively, with no significant difference( χ2=1.126, P=0.569), but the fatality rate for the low-dose rt-PA group was 7.0%(4/57), lower than 18.0%(9/50)( χ2=5.420, P=0.020)for the standard dose rt-PA group and 20.0%(8/58)for the conservative treatment group( χ2=5.048, P=0.025). The incidence of intracranial hemorrhage was 8.8%(5/57)for the low-dose rt-PA group, lower than 24.0%(12/50)for the standard-dose rt-PA group( P=0.032). The incidence of extracranial complications was 15.8%(9/57)for the low-dose rt-PA group, lower than 36.0%(18/50)for the standard-dose group( P=0.017). Conclusions:For elderly patients with acute cerebral infarction on maintenance hemodialysis, intravenous thrombolytic therapy with low dose rt-PA should be considered with caution.

Application value of psTg combined with lymph node ratio in prognosis of papillary thyroid cancer patients treated with 131I / 中华核医学与分子影像杂志

Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.

The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Preliminary study on the value of fetal MRI lung volume and mediastinal shift angle for predicting prognosis of left congenital diaphragmatic hernia / 中华放射学杂志

Objective:To explore the value of fetal lung volume and mediastinal shift angle (MSA) based on fetal MRI in predicting the prognosis of congenital diaphragmatic hernia (CDH).Methods:Fetuses with left CDH that did fetal MRI in Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine from September 2016 to January 2022 were retrospectively collected. There were 65 patients, and their gestational age was 29 (26, 35) weeks when they were diagnosed with left CDH by MRI. Observed fetal lung volume and MSA were measured based on fetal MRI, and observed/expected lung volume (o/eFLV) based on gestational age was calculated. The clinical data were collected from birth to discharge, and patients were divided into survival group and death group in case of prognosis at discharge, with 54 cases in the survival group and 11 cases in the death group. The student′s t test was used to compare the difference of o/eFLV and MSA between the survival group and the death group, and the receiver operating characteristic (ROC) curve was used to evaluate the value of o/eFLV and MSA in predicting the prognosis of left CDH. Results:The o/eFLV of the survival group was 51.5%±18.3%, higher than that of the death group (27.8%±4.4%), and the difference was significant ( t=8.29, P<0.001). The MSA of the survival group was 33.1°±1.2°, lower than that of the death group (41.8°±2.7°), and the difference was significant ( t=-11.15, P<0.001). The area under the ROC curve (AUC) of o/eFLV to predict the fetal survival or death was 0.939 (95%CI 0.851-0.983), the cutoff value was 33.8%, the sensitivity was 100%, the specificity was 88.9%. The AUC of MSA was 0.998 (95%CI 0.941-1.000), the cutoff value was 37.2°, the sensitivity was 100%, the specificity was 98.2%. Conclusions:The o/eFLV and MSA that were measured based on fetal MRI can effectively predict the fetus′s prognosis with left CDH.

Effects of horticultural therapy on social function for elderly inpatients with cognitive dysfunction / 中华行为医学与脑科学杂志

Objective:To investigate the effect of horticultural therapy on social function of elderly inpatients with cognitive dysfunction.Methods:Ninety inpatients with cognitive dysfunction who met the diagnostic criteria of ICD-10 were randomly divided into horticultural research group and control group, with 45 patients in each group.Finally, totally 82 completed the test with 41 in each group.Patients in the two groups were both given drug therapy according to clinical symptoms.At the same time, patients in the research group were given horticultural therapy 3 times a week, 90 minutes each section, for 12 weeks.Scale of social function in psychosis inpatients(SSPI) was used to assess the social function of the patients in the two groups were at baseline, 4, 8 and 12 weekends of the treatment.SPSS 25.0 software was used to conduct chi-square test and independent sample t-test for demographic data of the two groups, and repeated measures ANOVA was performed for SSPI score. Results:The results of repeated measure analysis of variance showed that the group main effect ( F=7.226, F=13.428, F=24.817, F=19.793) and interaction effect between time and group were all statistically significant ( F=29.644, F=42.937, F=53.246, F=67.215)(all P<0.01) in daily living ability (factor Ⅰ), mobility and interaction (factor Ⅱ), social activity skills score (factor Ⅲ) and total score.Simple effect analysis showed there were no statistically significant differences in each factor score and total score between the two groups at the baseline ( P>0.05), and there were statistically significant differences in each factor scores and total score at the end of the 8th weekend ((9.95±2.41), (10.39±3.38), (6.56±3.24), (26.90±7.88) vs (8.10±2.45), (6.88±3.48), (2.81±2.50), (17.78±6.96))and 12th weekend((10.27±2.16), (11.61±3.07), (7.88±3.08), (29.76±7.40) vs (7.56±2.41), (5.78±3.21), (2.34±2.02), (15.68±6.24)) (all P<0.01). The pair-to-pair comparison within the group showed that the differences in factor Ⅱ, factor Ⅲ and total score of the research group at the end of the 12th weekend ((11.61±3.07), (7.88±3.08), (29.76±7.40)) were higher than those at the baseline((8.59±3.93), (4.56±3.32), (22.02±8.35)), 4th weekend((9.07±4.14), (5.12±3.35), (23.59±8.51)), and 8th weekend((10.39±3.38), (6.56±3.24), (26.90±7.88))(all P<0.05). Factor Ⅰ (10.27±2.16) showed a statistically significant difference compared with the baseline (8.88±2.65) and 4th weekend (9.39±2.63)(both P<0.05). All the scores showed an upward trend. Conclusion:Horticultural therapy can improve the social function of elderly inpatients with cognitive impairment.

Efficacy of radiofrequency ablation combined with ozone therapy under CT guidance in the treatment of lumbar disc herniation / 中国基层医药

Objective:To investigate the efficacy of radiofrequency ablation combined with ozone therapy under CT guidance in the treatment of lumbar disc herniation.Methods:A total of 93 patients with lumbar disc herniation who were admitted to The First Hospital of Jiaxing from January 2019 to May 2022 were included in this study. They were randomly divided into an observation group ( n = 47) and a control group ( n = 46). The control group was treated with radiofrequency ablation and the observation group was treated with radiofrequency ablation combined with ozone therapy. Efficacy was compared between the two groups at 3 months after surgery. The pain was compared between the two groups before and 7 days and 3 months after surgery. Inflammatory factors were compared between the two groups before and 7 days after surgery. The lumbar spine function was compared between the two groups before and 3 months after surgery. Results:At 3 months after surgery, the excellent and good rate in the observation group was significantly higher than that in the control group [89.36% (42/47) vs. 71.74% (33/47), χ2 = 4.63, P < 0.05). At 7 days and 3 months after surgery, Visual Analogue Scale scores in the observation group were (2.91 ± 0.54) points and (1.32 ± 0.31) points, respectively, which were significantly lower than (3.76 ± 0.62) points and (2.08 ± 0.47) points in the control group ( t = 7.06, 9.22, both P < 0.001). At 7 days after surgery, serum interleukin-1β, interleukin-6, and tumor necrosis factor-α in the observation group were (0.24 ± 0.05) μg/L, (18.49 ± 3.47) ng/L, and (97.94 ± 17.43) ng/L, respectively, which were significantly lower than (0.37 ± 0.09) μg/L, (24.31 ± 4.12) ng/L, and (148.87 ± 20.13) ng/L, respectively in the control group ( t = 8.63, 7.37, 13.05, all P < 0.05). At 3 months after surgery, the Japanese Orthopedic Association score in the observation group was significantly higher than that in the control group [(25.68 ± 2.28) points vs. (21.17 ± 3.24) points, t = -7.78, P < 0.001], and the Oswestry Disability Index in the observation group was significantly lower than that in the control group [(9.84 ± 1.43) points vs. (13.46 ± 2.18) points, t = 9.49, P < 0.001]. Conclusion:Radiofrequency ablation combined with ozone therapy under CT guidance is highly effective on lumbar disc herniation. The combined therapy can reduce pain and inflammatory reactions in patients and improve lumbar function.

Effect of ACE2 deletion on vasoconstriction reactivity of aortic segments in mice with tourniquet shock / 中国病理生理杂志

AIM:To observe the effect of angiotensin-converting enzyme 2(ACE2)deletion on vasoconstric-tion reactivity of aortic segments in ACE2 knockout(KO)mice with tourniquet shock(TS).METHODS:The 8-month-old male mice with C57BL/6 background were divided into wild-type(WT)control group,WT-TS group,KO group and KO-TS group,with 10 mice in each group,of which five were used for determination of vascular reactivity,and the other five for the other assays.The hindlimbs of the mice in WT-TS group and KO-TS group were ligated with tourniquet for 2 h and loosened for 4 h.The mice in WT group and KO group were subjected to the same treatment except for tourniquet liga-tion.The vasoconstriction reactivity of the aorta was measured on tensiometer.The morphological damage of the aorta was evaluated by vascular histopathology.Western blot was used to detect the expression of AT1,MAS,ACE and ACE2 pro-teins in aorta.The serum levels of angiotensin(Ang)Ⅱ and Ang-(1-7)were determined by enzyme-linked immunosorbent assay.RESULTS:Compared with WT group,the mice in WT-TS group had lower vascular reactivity to norepinephrine(NE)and obvious vascular lesions.The expression of ACE protein increased significantly(P＜0.01),while the expres-sion of ACE2 decreased(P＜0.05).The expression of AT1 protein in aorta decreased significantly,the expression of MAS protein increased significantly,and the AT1/MAS ratio decreased(P＜0.01).Serum Ang II level increased,serum Ang-(1-7)level decreased,and Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.05).Compared with WT group,vascular reactivity in KO group increased at low concentration of NE(＜10-7 mol/L),and decreased at high concentration(＞10-7 mol/L)without vascular lesion.The expression levels of aortic AT1,MAS and ACE were all elevated(P＜0.05).The serum level of Ang Ⅱ increased(P＜0.05),but the level of Ang-(1-7)had no obvious change.Compared with KO and WT-TS groups,the aortic reactivity in KO-TS group subtracted apparently(P＜0.05),representing its curve shifting to the right obviously.The morphological damage aggravated slightly,and the expression of AT1 and ACE increased slightly in KO-TS group com-pared with WT-TS group(P＜0.05).However,the expression of MAS increased significantly in vascular tissue(P＜0.01).The serum levels of Ang Ⅱ and Ang-(1-7)further increased and decreased,respectively,and the Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.01).CONCLUSION:Deficiency of ACE2 induces severe aortic hyporeactivity to NE during TS,which may be related to the increased imbalance of renin-angiotensin system in ACE2 gene knockout mice.

Promoting effect of AGTR1 blocker olmesartan on the apoptosis of HTF and its mechanism / 中华实验眼科杂志

Objective:To study the effect and mechanism of angiotensin type 1 receptor (AGTR1) blocker olmesartan (OMS) on the apoptosis of human Tenon capsule fibroblasts (HTF).Methods:Tenon capsule tissues were obtained from patients during strabismus surgery in the Second Affiliated Hospital of Xi'an Jiaotong University.Primary HTF were cultured by explant culture.Primary cells were identified by vimentin immunofluorescence staining and flow cytometry.The fibrosis model of HTF was established using 10 ng/ml transforming growth factor-β2 (TGF-β2). The cells were divided into normal control group cultured in culture medium, TGF-β2 group in culture medium containing TGF-β2, TGF-β2+ OMS group in culture medium containing TGF-β2 and OMS, and OMS group in culture medium containing OMS, and were cultured for 48 hours.Cell apoptosis was detected by flow cytometry with annexin V/PI staining.The early apoptosis, late apoptosis, and total apoptosis rates were analyzed.The protein expression of procaspase-9, cleaved caspase-9, bax and bcl-2 in the mitochondrial apoptosis pathway was detected by Western blot.The activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) was detected by colorimetry.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (No.2019-014).Results:Primary HTF were successfully isolated and cultured.The cultured cells were long spindle-shaped and positive for vimentin.The expression rate of vimentin in the primary cells was greater than 99%.A statistically statistical difference was found in the early apoptosis rate, late apoptosis rate, and total apoptosis rate among the four groups ( F=24.92, 3.96, 41.82; all at P<0.05). The early and total apoptosis rates were significantly higher in TGF-β2+ OMS group than normal control group and TGF-β2 group, and the late apoptosis rate in TGF-β2+ OMS group was significantly higher than that of normal control group (all at P<0.05). There were statistically significant differences in cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 among the four groups ( F=4.40, 7.98, 4.61; all at P<0.05). The bax/bcl-2 expression was significantly increased in TGF-β2+ OMS group in comparison with normal control group, and the expressions of cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 were significantly elevated in TGF-β2+ OMS group compared with TGF-β2 group (all at P<0.05). LDH activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (783.99±79.97), (913.16±196.86), (2 529.06±240.21), and (2 134.29±138.96) μmol/(min·L), respectively, showing a statistically significant difference ( F=24.95, P<0.05). Compared with normal control group and TGF-β2 group, LDH activity in TGF-β2+ OMS group was increased, and the differences were statistically significant (both at P<0.05). SOD activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (50.35±0.97), (41.61±4.56), (28.88±3.26), and (37.61±4.83) μmol/(min·L), respectively, showing a statistically significant difference ( F=5.71, P<0.05). SOD activity was reduced in TGF-β2+ OMS group compared with normal control group and TGF-β2 group, reduced in OMS group compared with normal control group, and the differences were statistically significant (all at P<0.05). Conclusions:AGTR1 blocker OMS can promote the apoptosis of HTF effectively.Mitochondrial apoptosis pathway mediated by bax/bcl-2/caspase-9 and oxidative stress pathway are the potential mechanisms that OMS regulates the apoptosis of HTF.

Intermediary effect of benefit finding in the mindfulness level and coping style of acute cerebral infarction patients who received interventional therapy / 中国实用护理杂志

Objective:To observe the level of mindfulness and coping style in patients with acute cerebral infarction (ACI) after interventional therapy, and analyze the intermediary effect of benefit finding between them, so as to provide a theorectical basis of implement mindfulness intervention in clinical practice.Methods:The 130 patients with ACI after interventional treatment in the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021 were included in this cross-sectional survey study. The general data questionnaire, Five-factor Mindfulness Scale (FFMQ), Benefit Finding Rating Scale (BFS), and Simple Coping Style Questionnaire (SCSQ) were used to analyze the relationship between benefit finding, mindfulness level and coping style, and the intermediary effect of benefit finding between them.Results:The total FFMQ score of 130 ACI patients after interventional therapy was (123.34 ± 5.14) points. The BFS score, positive coping score and negative coping score were (49.73 ± 3.41), (20.35 ± 2.25), (13.18 ± 1.45) points, respectively. The level of mindfulness and benefit were positively correlated with positive coping ( r=0.687, 0.737, both P<0.05). The level of mindfulness and benefit were negatively correlated with negative coping( r=-0.654, -0.779, both P<0.05). It was found that mindfulness level played a partial intermediatory effect on positive coping and negative coping in ACI patients after interventional therapy, with contribution rates of 49.71% and 64.58%, respectively. Conclusions:Benefit finding plays a partial intermediary effect on the level of mindfulness and coping style of patients with ACI after interventional therapy.

Burden of multiple myeloma in China: an analysis of the Global Burden of Disease, Injuries, and Risk Factors Study 2019 / 中华医学杂志(英文版)

BACKGROUND@#There is limited data to comprehensively evaluate the epidemiological characteristics of multiple myeloma (MM) in China; therefore, this study determined the characteristics of the disease burden of MM at national and provincial levels in China.@*METHODS@#The burden of MM, including incidence, mortality, prevalence, and disability-adjusted life years (DALYs), with a 95% uncertainty interval (UI), was determined in China following the general analytical strategy used in the Global Burden of Disease, Injuries, and Risk Factors Study 2019. The trends in the burden of MM from 1990 to 2019 were also evaluated.@*RESULTS@#There were an estimated 347.45 thousand DALYs with an age-standardized DALY rate of 17.05 (95% UI, 12.31-20.77) per 100,000 in 2019. The estimated number of incident case and deaths of MM were 18,793 and 13,421, with age-standardized incidence and mortality rates of 0.93 (95% UI, 0.67-1.15) and 0.67 (95% UI, 0.50-0.82) per 100,000, respectively. The age-specific DALY rates per 100,000 increased to more than 10.00 in the 40 to 44 years age group reaching a peak (93.82) in the 70 to 74 years age group. Males had a higher burden than females, with approximately 1.5- to 2.0-fold sex difference in age-specific DALY rates in all age groups. From 1990 to 2019, the DALYs of MM increased 134%, from 148,479 in 1990 to 347,453 in 2019.@*CONCLUSION@#The burden of MM has doubled over the last three decades, which highlights the need to establish effective disease prevention and control strategies at both the national and provincial levels.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex

Objective@#Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. @*Methods@#We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. @*Results@#Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. @*Conclusion@#Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Transcatheter aortic valve implantation for native aortic valve regurgitation: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective     To evaluate the efficacy of transcatheter aortic valve implantation (TAVI) for native aortic valve regurgitation. Methods    Literature from The Cochrane Library, PubMed, EMbase, Cochrane Controlled Trials Registry, ClinicalTrials.gov and China Biomedical Literature Database from January 2002 to May 2021 were searched by computer. The literature on TAVI or transcatheter aortic valve replacement treatment for simple aortic reflux were collected. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and assessed the quality of the literature. Meta-analysis was performed using STATA 14.0 software. Results    A total of 15 studies including 1 394 patients were included. The Newcastle-Ottawa Scales of the studies were≥6 points. The success rate of prosthetic valve implantation was 72.0%-100.0%, and there was no report of serious complications such as surgical death, myocardial infarction, and valve annulus rupture. The 30-day all-cause mortality rate was 6.3% [95%CI (3.4%, 9.1%)]. The incidence of stroke within 30 days and the rate of postoperative permanent pacemaker implantation were 2.0% [95%CI (1.0%, 4.0%)] and 6.0% [95%CI (4.0%, 10.0%)], respectively, and were both within acceptable limits. Conclusion    For patients with simple high-risk aortic regurgitation, TAVI can obtain satisfactory treatment effects and has low postoperative complications rate, and it may be a potential treatment option for such patients.

Effect of ROS/NLRP3/Caspase-1 signaling pathway on the apoptosis of retinal pigment epithelial cells induced by high glucose / 中华实验眼科杂志

Objective:To investigate the effect of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome on the proliferation and apoptosis of human retinal pigment epithelial cell line ARPE-19 exposed to high glucose and its mechanism.Methods:ARPE-19 cells cultured in vitro were divided into normal control group and high-glucose group, and were cultured in conventional medium and medium containing 30 mmol/L glucose for 48 hours, respectively.The content of reactive oxygen species (ROS) were detected by fluorescent probe, and the activity of superoxide dismutase (SOD) and the concentration of malondialdehyde (MDA) were tested by biochemical assay.The cells of the two groups were cultured with 0, 2, 5, 10, 15 and 20 μmol/L NLRP3 inhibitor CY-09 for 48 hours, respectively.The proliferation rate of ARPE-19 cells under various concentrations of CY-09 treatment was detected by cell counting kit-8, and the appropriate concentration of CY-09 was determined.ARPE-19 cells were divided into normal control group, normal+ CY-09 group, high-glucose group and high glucose+ CY-09 group.The culture medium in the normal+ CY-09 group and high glucose+ CY-09 group was supplemented with 15 μmol/L CY-09.Flow cytometry was used to detect the apoptosis rate of each group, and Western blot was used to detect the relative expression levels of NLRP3, apoptosis-associated point protein (ASC), Caspase-1 precursor (pro-Caspase-1) and active fragments (cleaved-Caspase-1), B lymphocytoma-2 protein (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3 precursor (pro-Caspase-3) and active fragments (cleaved-Caspase-3). Results:The intensity of ROS fluorescence and MDA concentration were 120 020±3 245, (4.92±0.09) nmol/mg in the high-glucose group, which were both significantly higher than 35 426±811 and (1.78±0.03) nmol/mg in the normal control group, and the SOD activity was (35.65±1.22) μmol/(min·mg) in the high-glucose group, which was significantly lower than (74.96±1.41) μmol/(min·mg) in the normal control group, showing statistically significant differences between the two groups ( t=35.760, 46.960, 29.830; all at P<0.05). The proliferation rate of RPE cells in high-glucose group was significantly lower than that in normal control group, and the difference was statistically significant ( t=18.820, P<0.05). With the increase of CY-09 concentration, the proliferation rate of cells in the high-glucose group was gradually increased.The proliferation rates of cells treated with 10, 15 and 20 μmol/L CY-09 were all significantly higher than those treated with 0 μmol/L CY-09, showing statistically significant differences between them (all at P<0.05). The proliferation rates of cells treated with 15 μmol/L and 0 μmol/L CY-09 were not significantly different in the normal control group ( P>0.05). The apoptosis rate of cells in the high-glucose group was (21.68±0.41)%, which was significantly higher than (6.67±1.05)% in the normal control group and (13.96±0.07)% in the high-glucose+ CY-09 group, and the differences were statistically significant (both at P<0.05). The relative expression levels of NLRP3, ASC, cleaved-Caspase-1, cleaved-Caspase-3 and Bax proteins were significantly higher and the relative expression levels of Bcl-2 protein was significantly lower in the high-glucose group compared with the normal control group, and the differences were statistically significant (all at P<0.05). The relative expression levels of NLRP3, ASC, the active fragment of cleaved-Caspase-1, Bax and cleaved-Caspase-3 proteins were decreased and the relative expression levels of Bcl-2 protein were increased in the normal+ CY-09 group and high glucose+ CY-09 group compared with the normal control group and high glucose group, and the differences were statistically significant (all at P<0.05). Conclusions:NLRP3 inflammasome mediates the high glucose induced RPE cells apoptosis through ROS/NLRP3/Caspase-1 signaling pathway.

Characteristics of sepsis in the emergency department of a tertiary hospital in Tianjin: A 4-year retrospective analysis / 中华急诊医学杂志

Objective:Taking emergency department (ED) as a starting point, to analyze the epidemiological characteristics and mortality risk factors of sepsis, and to provide evidences for ED to carry out the strategy of "three early and two lower" for sepsis.Methods:Based on the ED and inpatient medical record management information platform of Tianjin Medical University Gernal Hospital, adult ED patients with sepsis from January 1, 2017 to December 31, 2020 were included according to the third international consensus definitions for sepsis and septic shock in 2016 and the consensus of Chinese experts on early prevention and blocking of sepsis in 2020. The epidemiological characteristics of patients were retrospectively analyzed. Chi-square test was used to compare the difference of age, sex, hospitalization times, length of stay, hospitalization cost and infection location between dead patients and survival patients, and a stepwise logistic regression model was used to analyze the influencing factors of mortality in hospitalized patients with ED sepsis.Results:A total of 7 494 patients with sepsis in ED were included in this study, and the annual and monthly component ratios varied from 3.8‰ to 6.1‰ and 2.0‰ to 9.0‰, respectively. The main characteristics of patients with sepsis in ED were as follows: 40-69 years old (46.0%), male (59.0%), mostly diagnosed with sepsis (96.8%), mainly treated with urban health insurance (59.6%), and ED diagnosis and treatment fees of 2 000-8 000 Yuan (51.1%). The mortality of hospitalized patients with ED sepsis was 24.4% and that of hospitalized patients with septic shock was 28.8%. The main characteristics of hospitalized patients with ED sepsis were as follows: most of them were male (56.2%) patients over 70 years old (56.0%), most of them were diagnosed with sepsis (94.0%) and hospitalized for the first time (76.0%), the median hospitalization time was 15 d, most of them were hospitalized under urban health insurance (65.2%), and the median hospitalization fees was 47 000 Yuan. The risk factors of death were influenced by age and length of stay. Patients aged 70 years or older had a higher risk of death than those aged from 18 to 39 years, and patients with a length of stay of more than 7 d had a lower risk of death than those with a length of stay of shorter than 7 d. The primary infection focus were mainly respiratory and urinary systems, while the death rate of patients with hematological and abdominal infections was relatively high, and the difference was statistically significant ( P<0.01). Respiratory and abdominal infections were risk factors for death in patients with ED sepsis. Conclusions:The composition ratio of sepsis in ED patients is not regular in time, so vigilance of sepsis in elderly men and patients with respiratory system, blood system, urinary system and abdominal infections should be constantly raised. Patients with sepsis who are older, hospitalized more frequently, hospitalized for a shorter time, and infected in the respiratory system or abdomen have a higher risk of death.