Disulfide bridge-targeted metabolome mining unravels an antiparkinsonian peptide

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Effect of Modified Cangfu Daotantang on Glucose and Lipid Metabolism in Simple Obese Children with Phlegm Dampness and Stagnation / 中国实验方剂学杂志

ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation. MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group， and the even number was included in the basic treatment group， with 30 cases in each group. On the basis of signing the informed consent notice， the treatment group was given modified Cangfu Daotantang combined with basic treatment， while the control group was only given basic treatment. After three months of treatment， the body mass index （BMI）， glucose and lipid metabolism level ［total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， fasting plasma glucose （FPG）， fasting insulin （FINS）， and homeostasis model assessment-insulin resistance （HOMA-IR）］， the change in the total score of traditional Chinese medicine （TCM） syndromes， and the effective rate of treatment were observed and compared. ResultAfter treatment， the BMI of the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the BMI level in the observation group decreased significantly （P<0.05）. After treatment， the levels of TC， TG， and LDL-C in the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the levels of TC， TG， and LDL-C in the observation group decreased significantly （P<0.05）. In addition， the level of TC in the observation group improved significantly compared with that in the control group （P<0.01）. The levels of FPG， FINS， and HOMA-IR in the observation group and the control group were significantly lower than those before treatment （P<0.05）. After treatment， compared with the control group， the levels of FPG， FINS， and HOMA-IR in the observation group were significantly reduced （P<0.05）. The level of FPG in the observation group was significantly improved compared with that in the control group （P<0.01）. After treatment， the total score of TCM syndromes in the two groups decreased significantly （P<0.01）. Compared with the control group， the total score of TCM syndromes in the observation group was lower （P<0.01）. After treatment， the total effective rate of treatment was 86.67% （26/30） in the observation group and 73.33% （22/30） in the control group. By rank sum test， the total effective rate of the observation group was better than that of the control group （Z=-2.100， P<0.05）. ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value， which is worth further in-depth research and promotion.

Expression of CD226 in the small intestinal group 3 innate lymphoid cells (ILC3) in mice / 细胞与分子免疫学杂志

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.

Associations between educational burden and depression and anxiety symptoms among middle school students in Taizhou City / 中国学校卫生

Objective@#To investigate the prevalence of depression and anxiety symptoms among middle school students in Taizhou, Zhejiang Province, and its associations with their educational burden, so as to provide a theoretical reference for making more targeted psychological interventional measures.@*Methods@#A cross sectional study was conducted by multi stage cluster sampling from September to November 2022 from 30 schools in five districts and counties of Taizhou, with a final sample of 8 128 junior and senior high school students completing the online surveys on the Questionnaire Star platform. The Educational Stress Scale for Adolescents (ESSA) was used to measure academic stress; the Child Depression Inventory (CDI) and the Generalized Anxiety Disorder Scale (GAD-7) were used to screen students depression and anxiety, respectively. The relationships between educational burden and depression and anxiety symptoms were analyzed by Logistic regression models.@*Results@#The prevalence of depression and anxiety were 19.3% and 11.1%, respectively. The average score of middle school students study pressure was (52.8±11.5). The number of extracurricular classes was <1, the time length of extracurricular courses was <1 hour per day, and students averagely spend 3.6 hours per day on homework assigned by school teachers. Nearly 30.0% students had ≤0.5 of discretionary time school days and 28.5% students had ≤2 on weekends. About 30.8% students though they do worse in their academic performance. According to the results of binary Logistic regression analysis, after controlling the demographic variables, the score in Study Pressure Scale, the number of extracurricular classes, the volume of homework and the time length of extracurricular courses were positively associated with depression and anxiety ( OR =1.09, 1.07, 1.08, 1.05, 1.04, 1.08, 1.08, 1.08, 1.06, 1.09, 1.07, 1.47, 1.34, 2.84 ; 1.08, 1.06, 1.08, 1.04, 1.03, 1.05, 1.05, 1.05, 1.05, 1.07, 1.06, 1.48, 1.23, 1.75, P <0.05). Students with overage grades had a higher risk of depression symptoms ( OR=1.34, P <0.05).@*Conclusions@#Academic burden has negative effects on depression and anxiety of students in Taizhou. It is advisable to alleviate academic stress, so as to improve the mental health of students.

Correlation of cognitive function and clinical characteristics in adolescent depressive disorder patients with self-injury behavior / 中华行为医学与脑科学杂志

Objective:To investigate the correlation between cognitive function and addiction, impulsivity, and anhedonia in adolescent depressive disorder patients with self-injury behavior.Methods:From September 2021 to October 2022, adolescents with depressive disorders who visited the outpatient department of the Qingdao Mental Health Center were enrolled and divided into self-injury group and non self-injury group based on the presence or absence of self-injury behaviors, each with 60 participants.A self-compiled general information questionnaire, the 17 items Hamilton depression rating scale (HAMD-17), the Ottawa self-injury inventory (OSI), the Chinese version of the Barratt impulsiveness scale (BIS-11), and the temporal experience of pleasure scale(TEPS) were used to evaluate both groups.The Chinese brief cognitive test(C-BCT) was used to assess cognitive function in both groups.SPSS 26.0 software was used for statistical analysis, including t-test, χ2 test, Pearson correlation analysis, and multiple linear regression analysis. Results:The self-injury group had higher scores for OSI addiction factors (9.43±8.29) and BIS-11 (67.09±11.48) compared to the non self-injury group (OSI addiction factor scores: 0, BIS-11 scores: 53.70±7.12, t=6.22, 5.91, both P<0.05). TEPS score and C-BCT scores in various dimensions were lower in the self-injury group than those in the non self-injury group ( t=-2.93, -2.01, -2.88, -2.20, -5.35, all P<0.05). Information processing speed was negatively correlated with BIS-11 score ( r=-0.296, P<0.05), and attention score were negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.303, -0.561, both P<0.05) and positively correlated with TEPS score ( r=0.364, P<0.05), including a positive correlation with the scale of anticipatory anhedonia score ( r=0.318, P<0.05). Working memory score was negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.312, -0.416, both P<0.05). Comprehensive ability and executive function scores were negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.308, -0.679, both P<0.05), and positively correlated with TEPS score ( r=0.304, P<0.05). Multiple linear regression analysis showed that BIS-11 scores were influencing factors of C-BCT dimensions ( β=-0.260, -0.592, -0.557, -1.797, t=-2.150, -3.314, -2.285, -5.165, all P<0.05). Conclusion:In adolescent depressive patients with self-injury, cognitive function is correlated with addiction, impulsivity and anhedonia, among which impulsivity is a risk factor for cognitive function.

Associations between the sense of school belonging and mental health status among medical students during the post-epidemic period / 中华医学教育探索杂志

Objective:To explore the status of medical students' sense of school belonging and its relationship with depression and anxiety symptoms in the context of COVID-19 prevention and control.Methods:An online questionnaire survey was conducted among 1 629 full-time students from 8 medical universities. The 18-item psychological sense of school membership scale (PSSM-18), 9-item patient health questionnaire (PHQ-9), and 7-item generalized anxiety disorder scale (GAD-7) were used as measurements. Spearman correlation coefficients were used to analyze the correlations between PSSM-18, PHQ-9, and GAD-7 scores. Logistic regressions were used to analyze the impact of lack of school belonging on depression and anxiety symptoms.Results:The mean score of school belonging was (77.31±14.12), and the detection rates of depression and anxiety symptoms were 25.97% (423/1 629) and 21.92% (357/1 629), respectively. PSSM-18 score was negatively correlated with PHQ-9 scores ( r=-0.52, P<0.001) and GAD-7 scores ( r= -0.49, P < 0.001). After adjusting for covariates, students with low school belongingness had 4.33 times the risk of depression symptoms ( OR=4.33, 95%CI=2.48-7.43) and 5.85 times the risk of anxiety symptoms ( OR= 5.85, 95%CI=3.76-8.15) compared to students with high school belongingness. Conclusion:Lack of school belonging increases the risk of depression and anxiety symptoms. Under the normalization of COVID-19 prevention and control, the school should strengthen health education and support services to improve the students' sense of belonging and alleviate their mental health problems.

Clinical and molecular genetic study of a Chinese Han family with X-linked retinoschisis / 中华实验眼科杂志

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

A qualitative study on the influencing factors of parents′ participation in emotional management of adolescents with affective disorder / 中国实用护理杂志

Objective:To understand the barriers and facilitators to parental involvement in emotionally disturbed adolescents′ emotion management and to provide a basis for healthcare professionals to develop interventions for parental involvement in emotionally disturbed adolescents′ emotion management.Methods:Use of purposive sampling method from July to December 2021, 16 face-to-face semi-structured in-depth interviews were conducted with fathers or mothers of adolescents with affective disorders from the Third Hospital of Daqing City, and the data were analyzed using the Colaizzi 7-step analysis method.Results:Refining the theme from two aspects, one was the hindering factors: parents′ own factors including lack of knowledge about the disease, little time for companionship, poor emotional control, inappropriate communication style, and poor couple relationship; the child′s own factors including pathological factors, personality; environmental factors including academic stress, interpersonal relationships; economic factors including high cost of treatment, life stress. The other was the facilitating factors: support from others including family support, professional help; positive coping including finding coping strategies, change of mindset.Conclusions:Healthcare professionals should pay attention to these influencing factors and construct a program for parental involvement in emotionally disturbed adolescents′ emotion management from various aspects, so that parents can actively participate in their children′s emotion management and promote the rehabilitation of emotionally disturbed adolescents.

Factors affecting decreased ovarian reserve among women of childbearing age / 预防医学

Objective@#To investigate the factors affecting decreased ovarian reserve (DOR) among women of childbearing age, so as to provide insights into prevention of DOR.@*Methods@#Women with DOR at ages of 18 to 40 years that were admitted to Department of Gynecology, Ningbo Women and Children's Hospital during the period from January 2021 to June 2022 were recruited (DOR group), while healthy women at ages of 18 to 40 years during the same period served as normal controls. Participants' demographics, exercise, diet, previous medical history, childbearing history and menstruation were collected using questionnaire surveys. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and estradiol (E2) levels were tested. Factors affecting DOR were identified among women of childbearing age using a multivariable logistic regression model.@*Results@#There were 200 participants in the DOR group, with a median (interquartile range) age of 32 (9) years, and 200 participants in the normal group, with a median (interquartile range) age of 29 (12) years. Multivariable logistic regression analysis showed that underweight (OR=2.935, 95%CI: 1.374-6.269), overweight/obesity (OR=2.612, 95%CI: 1.335-5.065), high-oil-high-glucose-high-salt diet (OR=2.653, 95%CI: 1.616-4.357), menstrual disorder (OR=1.977, 95%CI: 1.284-3.041) and lack of exercise (OR=3.392, 95%CI: 2.052-5.606) were statistically correlated with the development of DOR among women of childbearing age.@*Conclusions@#Underweight, overweight/obesity, high-oil-high-glucose-high-salt diet, menstrual disorder and lack of exercise are factors affecting the development of DOR among women of childbearing age.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Changes in HIV prevalence and intervention service utilization among MSM under sentinel monitoring in Taizhou of Zhejiang Province / 上海预防医学

ObjectiveTo analyze the changes in HIV， syphilis and hepatitis C prevalence among men who have sex with men （MSM） in Taizhou City， Zhejiang Province from 2017 to 2022， and the utilization of HIV intervention services and its influencing factors. MethodsMSM participants were recruited from HIV sentinel surveillance in Taizhou through snowball sampling method. Participants’ socio-demographic characteristics， sexual behavior characteristics， knowledge of HIV and utilization of HIV intervention services were collected and statistically described by questionnaire survey. Blood samples from MSM sentinel population were also collected for HIV， syphilis， and HCV antibody testing. Multivariate logistic regression analysis was used to analyze the influencing factors for utilizing HIV intervention services among MSM. ResultsA total of 2 499 MSM were included in the analysis from 2017 to 2022， with HIV prevalence of 5.8%， syphilis prevalence of 4.0%， and HCV prevalence of 0.6%. The infection rate， proportion of homosexual anal sex and heterosexual sex showed a decreasing trend， while the proportion of condom use during homosexual anal sex， condom publicity and distribution， AIDS consultation and testing， acceptance of peer education， and online temporary homosexual sex showed an increasing trend. All these differences were statistically significant. Multivariate logistic regression analysis showed that COVID-19 epidemic （aOR=1.66， 95%CI：1.04‒2.64） and HIV knowledge awareness （aOR=2.57， 95%CI：1.22‒5.40） were positively correlated with increased acceptance of condom publicity and distribution， and utilization of AIDS counseling and testing. Those who sought male sexual partners through offline route （aOR=3.44， 95%CI： 1.16‒10.21）， and had a history of sexually transmitted diseases within one year （aOR=5.47， 95%CI： 1.04‒28.76） were positively correlated with community-based methadone maintenance therapy， clean needle provision and exchange services， while COVID-19 epidemic （aOR=0.35， 95%CI： 0.14‒0.88） was negatively correlated with the utilization of these services. COVID-19 epidemic （aOR=2.11， 95%CI： 1.54‒2.89）， HIV knowledge awareness （aOR=2.09， 95%CI： 1.08‒4.02）， offline search for male sexual partners （aOR=1.47， 95%CI： 1.03‒2.11）， and awareness of HIV infection of sexual partners （aOR=2.09， 95%CI： 1.62‒2.69） were positively correlated with the increased use of peer education service， while married or cohabited （aOR=0.73， 95%CI： 0.55‒0.98） and VCT （aOR=0.61， 95%CI： 0.46‒0.82） were negatively correlated with utilization of peer education service. ConclusionHIV infection rate of sentinel MSM population in Taizhou decreases， while the utilization of HIV intervention services increases in general. Targeted measures should be developed according to the changes in sexual behavior and HIV intervention services among MSM populations in Taizhou to improve the HIV intervention services for the MSM population.

Qualitative Study on the Psychological Experience of Cancer Patients after Withdrawing from Drug Clinical Trials / 中国医学伦理学

【Objective:】 To understand the real psychological feelings of cancer patients after withdrawing from drug clinical trials, and provide reference for clinical healthcare professionals to serve personalized care for patients in the transitional period after withdrawing from drug clinical trials. 【Methods:】 With the descriptive phenomenology method, 11 subjects who withdrew from drug clinical trials in the oncology department of a tertiary hospital in Shandong Province were selected by intentional sampling method to conduct semi-structured in-depth interviews. Colaizzi seven-step analysis method was used to analyze and sort out records, and refine themes. 【Results:】 The psychological experiences of cancer patients after withdrawing from drug clinical trials were summarized into four themes: benefits of participating in clinical trials, losses of withdrawing from clinical trials, attitudes towards future treatment, and expectations of receiving help. 【Conclusion:】 Cancer patients face great psychological pressure after withdrawing from drug clinical trials and require deep emotional support and humanistic care. Nursing staff should take personalized care measures to meet the special problems of patients’ psychological needs, so as to help patients smoothly pass through the withdrawal stage and enter subsequent treatment.

Characteristics analysis of HBV serological markers of NAT reactive blood donors under different HBsAg status / 中国输血杂志

【Objective】 To investigate the characteristics of HBV serological markers of NAT reactive blood donors under different HBsAg status. 【Methods】 NAT reactive samples, with HBsAg-, HBsAg+ /retest - and HBsAg+ by single reagent were collected from September 2021 to May 2022 in our laboratory. The TMA non-reactive samples were retested by Roche PCR, then HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were detected by ECLI for statistical analysis. 【Results】 A total of 66 samples were collected, among which 55 were HBsAg-/NAT+. The positive rate of anti-HBc, anti-HBs+ anti-HBc, anti-HBe+ anti-HBc was 87.3% (48/55), 43.6% (24/55) and 45.5% (25/55), respectively. The positive rate of anti-HBs was 10.9% (6/55) and the overall negative rate was 1.8% (1/55). In 7 HBsAg+ initially/retest -/NAT+ samples, the positive rate of anti-HBc was 100%(7/7), and the positive rate of anti-HBe+ anti-HBc was 71.4%(5/7). In 4 HBsAg+ /NAT+ samples by single reagent, the positive rate of HBsAg+ anti-HBs+ anti-HBe+ anti-HBc was 50% (2/4), and positive rate of anti-HBe+ anti-HBc was100% (4/4). Samples, not reactive to TMA discriminatory and anti-HBc negative, were also non-reactive to individual PCR retest. There were significant differences in the positive rates of anti-HBe+ anti-HBc between HBsAg-/NAT+ samples and HBsAg+ /NAT+ (single reagent) samples (P<0.05). 【Conclusion】 Most HBsAg-/NAT+ blood donors were occult hepatitis B virus infection.The anti-HBe+ anti-HBc positive were correlated with HBV infection status. Non-reactivity discriminated by TMA plus anti-HBc negative do not exclude HBV DNA non-reactivity.

Detection results of blood donors with HBsAg reactivity to single reagent: a retrospective analysis / 中国输血杂志

【Objective】 To retrospectively analyze the detection results of blood donors with HBsAg reactivity to single reagent detected by enzyme-linked immunosorbent assay (ELISA) in our center, so as to provide basis for further consolidating the blood donor team. 【Methods】 Samples of blood donors who had been deferred for at least 6 months due to HBsAg reactivity to sole ELISA assay were collected, and HBsAg ELISA and NAT were further performed. Meanwhile, HBsAg/HBsAb/HBeAg/HBeAb/HBcAb were detected by Roche electrochemiluminescence immunoassay, and the results were statistically analyzed. 【Results】 Among these 51 selected samples, 45 were negative to two assays, 6 were reactive to sole assay, with reactivity-yield rate at 11.76% (6/51). The results of NAT/ECLIA were all negative. For five indicators of hepatitis B virus infection, 23 samples were all negative and 28 were partially positive, mainly anti-HBs, anti-HBc and anti-HBe. 【Conclusion】 The follow-up detection of HBsAg ELISA sole-reagent reactive samples, supplemented with the detection of HBV serological markers, can reduce the number of deferred blood donors, increase the willingness to donate blood again, and protect the rights and interests of blood donors.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury / 中华医学杂志(英文版)

BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

A case-control study on the risk of stroke in the elderly in Shanghai community / 上海预防医学

ObjectiveTo explore the risk factors of stroke， and to provide reference for the prevention and health management of stroke. MethodsFrom February 2022 to March 2022， four community residents over 60 years old with stroke in Shanghai were randomly selected as the case group （n=100）， and non-stroke residents were selected as the control group （n=100）. The survey was in the form of questionnaires to record and compare the age， body mass index （BMI）， blood lipids， blood pressure-related indicators， family history of other diseases， living habits， mood and sleep conditions of all subjects. The value of predicting the incidence of stroke among the elderly in Shanghai community was analyzed by receiver operating characteristic （ROC）， and the influencing factors of stroke were analyzed by logistic model. ResultsBMI， hypertension， heart disease， diabetes， transient ischemic attack （TIA）， dyslipidemia， family history of stroke， smoking， lack of exercise or only light physical labor， SBP， DBP， TG levels were significantly higher in the case group （P<0.05）. The level of HDL-C was significantly lower than that in the control group （P<0.05）. BMI， SBP， DBP， TG， HDL-C predicted the incidence of stroke by ROC analysis （P<0.05）. Logistic regression analysis showed that BMI≥23.820 kg·m-2， heart disease， diabetes， TIA， dyslipidemia， family history of stroke， smoking， lack of exercise or only light physical labor， SBP≥139.535 mmHg， DBP≥89.605 mmHg， TG≥1.565 mmol·L-1 and HDL-C≤1.105 mmol·L-1 were risk factors for stroke （P<0.05）. ConclusionPhysical health status including blood lipids and blood pressure， family history of certain diseases， and living habits could be important risk factors for stroke in the elderly in Shanghai community. Preventive intervention measures for the above factors have important clinical significance.

Effect of music therapy on depression and anxiety in patients with maintenance hemodialysis: a randomized controlled study / 中华肾脏病杂志

Objective:To investigate the effect of music therapy on depression and anxiety status in maintenance hemodialysis (MHD) patients.Methods:The study was a single-center, open, and randomized controlled trial. The patients with regular hemodialysis of more than 3 months and the Beck depression inventory (BDI) scores ≥10 in China Rehabilitation Research Center from March 1 to April 24, 2021 were selected. Random envelope method was used to divide the enrolled patients into music group and control group. The music therapist selected the treatment music and established the preset repertoire library in the music therapy programs, and the total duration of music was about 2 hours. The music group received listening music therapy of 1.0 to 1.5 hours 3 times a week during routine hemodialysis treatment, while the control group only received routine hemodialysis treatment. All the enrolled patients completed treatment of 8 weeks. The BDI and state-trait anxiety inventory (STAI) were used to assess the psychological status of MHD patients before and after treatment.Results:A total of 64 MHD patients were enrolled, aged (59.19±11.61) years old, among whom 38 patients (59.38%) were males. There were 32 patients in the music group and 32 patients in the control group. BDI scores [2 weeks (9.81±6.25) scores, 8 weeks (8.30±8.49) scores, F=49.75, P<0.001] and STAI scores [2 weeks (49.30±7.27) scores, 8 weeks (47.07±7.39) scores, F=13.09, P<0.001] in the music group decreased significantly after 2 weeks of treatment and remained stable for 8 weeks. After treatment, the BDI scores in the music group were significantly lower than those in the control group [2 weeks (9.81±6.25) scores vs (14.13±7.33) scores, t=-2.53, P=0.014; 8 weeks (8.30±8.49) scores vs (12.56±5.67) scores, t=-2.34, P=0.023], and STAI scores in the music group were significantly lower than those in the control group [2 weeks (49.30±7.27) scores vs (54.00±8.36) scores, t=-2.06, P=0.043; 8 weeks (47.07±7.39) scores vs (51.34±8.87) scores, t=-2.06, P=0.044]. Conclusion:Music therapy can improve depression and anxiety of MHD patients quickly and effectively.

Relationship between elevated fibrinogen and early neurological deterioration in type 2 diabetes mellitus patients with acute cerebral infarction / 中华老年医学杂志

Objective:To investigate the relationship between plasma fibrinogen(FIB) levels and early neurological deterioration(END) in elderly patients with type 2 diabetes mellitus(DM) after acute cerebral infarction(ACI).Methods:136 ACI patients admitted to the neurology department of our hospital from January 2018 to December 2019 were included as study subjects.Patients were divided into an END group and a non-END group based on whether END occurred.Univariate and multivariate analyses were conducted to assess the relationship between FIB and END.Elderly patients with concurrent ACI and DM were divided into an END group(18 cases)and a non-END group(26 cases)for propensity score matching analysis.After matching adjustment, age, sex, hypertension, TOAST classification and FIB were analyzed by multivariate Logistic regression.Results:Among 136 patients with ACI, 38(27.9%)had END and 98(72.1%)did not have END and the END group had higher values or percentages than the non-END group in age[(62.3±2.4)ys and(59.2±1.8)ys, t=2.035, P=0.044], history of hypertension(76.3% and 57.1%, χ2=4.295, P=0.038), history of diabetes(47.4% and 26.5%, χ2=5.433, P=0.020), NIHSS score[(8.5±5.7)and(6.1±4.6), t=2.548, P=0.012], TOAST classification(large artery atherosclerosis: 65.8% vs.40.8%, cardioembolism: 5.3% vs.10.2%, small artery occlusion: 23.7% vs.23.5%, other determined cause: 2.6% vs.20.4%, undetermined cause: 2.6% vs.5.1%, χ2=10.314, P=0.035), blood glucose[(8.89±1.28)mmol/L and(7.36±1.64)mmol/L, t=6.048, P=0.000]and FIB level[(3.57±1.33)g/L and(3.07±1.14)g/L, t=2.236, P=0.027]. Multiple regression analysis showed that higher FIB levels were not associated with END( P>0.05). Propensity score matching analysis of 44 patients with concurrent ACI and DM showed that history of hypertension, NIHSS score and FIB level before matching were significantly higher in the END group than in the non-END group( P<0.05)and FIB was higher in the END group than in the non-END group after matching.Multiple regression analysis showed that FIB was significantly associated with END. Conclusions:Increased FIB levels are positively correlated with END in patients with diabetes following acute ischemic stroke and possess good predictive value.

Role of inflammation and apoptosis in right ventricular dysfunction induced by injurious mechanical ventilation in rats / 中华危重病急救医学

Objective:To investigate whether myocardial inflammation and apoptosis are involved in right ventricular dysfunction (RVD) induced by injurious mechanical ventilation with high tidal volume (VT) in rats.Methods:Total 30 adult male SD rats were randomly divided into the control group (CON group), the low VT ventilation group (LVT group) and the injurious mechanical ventilation group (HVT group), with 10 rats in each group. The CON group was maintained spontaneous breathing, the LVT group and HVT group were ventilated with different VT 6 mL/kg and 20 mL/kg for 4 hours, respectively. The right jugular vein and the left carotid artery were catheterized and connected with the PowerLab biological signal acquisition and analysis system to record heart rate (HR), mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (+dp/dt max). Echocardiography was performed to measure left ventricular end-diastolic diameter (LVEDd), right ventricular end-diastolic diameter (RVEDd), tricuspid annulus plane systolic migration (TAPSE) and myocardial performance index (MPI). The rats were sacrified by cervical dislocation. Specimens of right ventricle tissues were taken for hematoxylin-eosin (HE) staining, and morphological changes of right ventricle tissues were observed under light microscope. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3, apoptosis-related proteins Bax and Bcl-2.Results:HR, MAP, +dp/dt max gradually decreased, while RVSP gradually increased in different group with the increase of VT ventilation. There was no significant difference between the CON group and LVT group. However, there was a statistically significant difference with respect to these index in HVT group as compared to CON group and LVT group [HR (bpm): 397.6±5.7 vs. 433.0±4.8, 441.6±7.8; MAP (mmHg, 1 mmHg≈0.133 kPa): 102.0±2.4 vs. 108.5±2.2, 110.6±2.1; +dp/dt max (mmHg/s): 2 357.65±62.80 vs. 2 661.27±55.62, 2 679.43±75.13; RVSP (mmHg): 28.8±1.0 vs. 22.6±10.8, 21.9±0.4; all P < 0.05]. Echocardiography findings showed that RVEDd/LVEDd and MPI gradually increased, TAPSE gradually decreased in different group with the increase of VT ventilation. There was no significant difference between the LVT group and CON group. However, there was a statistically significant difference with respect to these indexes in HVT group as compared to the CON group and LVT group [RVEDd/LVEDd: 0.36±0.02 vs. 0.26±0.01, 0.23±0.02; MPI: 1.23±0.03 vs. 0.84±0.04, 0.86±0.03; TAPSE (mm): 1.65±0.03 vs. 1.88±0.02, 1.91±0.04; all P < 0.05]. Histopathological observation of the right ventricle tissue showed that myocardial cells of the rats in the CON group were orderly arranged and uniformed in size. In the LVT group, there was a small amount of inflammatory cell infiltration in the myocardial interstitium, while in the HVT group, the myocardial cell arrangement was obviously disordered, the structure was obviously damaged, and more inflammatory cell infiltration was found. RT-PCR and Western blotting analysis showed that the mRNA and protein expressions of IL-6, TNF-α, caspase-3 and Bax in HVT group were significantly higher than those in the LVT group and CON group [mRNA expression (2 -ΔΔCt): IL-6 were 1.97±0.07 vs. 1.09±0.02, 1.02±0.03, TNF-α were 1.69±0.10 vs. 1.10±0.03, 1.05±0.04, caspase-3 were 1.82±0.09 vs. 1.08±0.02, 1.06±0.03, Bax were 2.19±0.14 vs. 1.07±0.03, 1.04±0.03; protein expression (gray value): IL-6 were 0.64±0.02 vs. 0.38±0.03, 0.31±0.04, TNF-α were 0.50±0.04 vs. 0.16±0.01, 0.15±0.01, caspase-3 were 0.58±0.02 vs. 0.29±0.01, 0.25±0.02, Bax were 0.50±0.03 vs. 0.21±0.01, 0.26±0.02; all P < 0.05], and the mRNA and protein expressions of Bcl-2 in the HVT group were lower than those in the LVT group and CON group [mRNA expression (2 -ΔΔCt): 1.23±0.05 vs. 1.43±0.05, 1.50±0.08; protein expression (gray value): 0.42±0.02 vs. 0.62±0.03, 0.65±0.03, all P < 0.05]. Conclusion:Myocardial inflammation and apoptosis may be involved in RVD induced by injurious mechanical ventilation.

Clinical characteristics, treatment and prognosis of myelodysplastic syndrome complicated by acute cerebral infarction / 中国基层医药

Objective:To investigate the clinical characteristics, imaging features, treatment, prognosis, and possible causes of myelodysplastic syndrome complicated by acute cerebral infarction.Methods:The clinical data of four patients with myelodysplastic syndrome complicated by acute cerebral infarction who received treatment at Peking University International Hospital and Beijing Jingcheng Boai Hospital from January to December 2021 were retrospectively analyzed.Results:All four patients experienced myelodysplastic syndrome complicated by acute cerebral infarction for the first time. They were aged 60-69 years, with a median age of 65 years. Bone marrow suppression occurred in the four patients with myelodysplastic syndrome after chemotherapy, resulting in a remarkable reduction in the number of platelets. All four patients had just been transfused with platelets before the onset of myelodysplastic syndrome complicated by acute cerebral infarction. The main clinical manifestations were dyskinesia, language disorder, paresthesia, and dizziness. Three patients had multiple foci, two of them involved bilateral cerebral hemispheres, and only one patient had a single focus. Circulation improvement and symptomatic treatment were given after admission. Two patients with cerebral hernia died, and two patients were discharged after improvement.Conclusion:The pathogenesis of myelodysplastic syndrome complicated by acute cerebral infarction is complex. It includes many causes rather than common risk factors for stroke. Myelodysplastic syndrome complicated by acute cerebral infarction is rare in the clinic. It is difficult to treat, is serious, and has a poor prognosis.