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.

Analysis of cell mutation types of colorectal neuroendocrine tumors / 基础医学与临床

Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Application and research progress of nanotechnology in atherosclerosis / 实用医学杂志

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.

Exploring the efficacy of roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with diabetic kidney disease based on microvascular complications / 中国医师进修杂志

Objective:To investigate the effect of roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with diabetic kidney disease (DKD), and its effects on iron metabolism, microinflammation status and microvascular complications.Methods:The clinical data of 89 hemodialysis renal anemia patients with DKD from January 2020 to October 2021 in Beijing Geriatric Hospital were retrospectively analyzed. Among them, 44 patients (control group)were treated with recombinant human erythropoietin and levocarnitine for renal anemia, and 45 patients (study group) were treated with recombinant human erythropoietin, levocarnitine and roxadustat for renal anemia. Both groups were treated for 3 months. The efficacy was compared between two groups. The laboratory indexes were measured before treatment and after 1, 3 months of treatment, including anemia related indexes such as hemoglobin, red blood cell count and mean corpuscular volume (MCV); iron metabolism indexes such as serum iron, ferritin and transferrin saturation (TSAT); inflammatory indexes such as interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). The adverse reactions were recorded. The patients were followed up for 1 year after treatment, the incidence of diabetic microvascular complications, including diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR), was recorded.Results:The total effective rate in study group was significantly higher than that in control group: 93.33% (42/45) vs. 77.27% (34/44), and there was statistical difference ( χ2 = 4.60, P<0.05). There were no statistical differences in the laboratory indexes before treatment between two groups ( P<0.05); the hemoglobin, red blood cell count, MCV, serum iron, ferritin and TSAT after 1 and 3 months of treatment in study group were significantly higher than those in control group, the IL-8, CRP and TNF-α were significantly lower than those in control group, and there were statistical differences ( P<0.01 or <0.05). There was no significant difference in the incidence of adverse reactions between two groups ( P>0.05). After 1 year follow-up, 2 cases were lost in study group and 3 cases in the control group. The incidence of DR and DPN in study group were significantly lower than those in control group: 0 vs. 14.63% (6/41) and 2.33% (1/43) vs. 19.51% (8/41), and there were statistical differences ( χ2 = 4.75 and 4.81, P<0.05). Conclusions:Roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with DKD is reliable and safe, and can effectively relieve anemia symptoms, improve iron metabolism, reduce inflammatory response, and reduce the risk of diabetic microvascular complications.

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.

HBV serological characteristics between NRR samples and OBI samples of from blood donors in Hefei / 中国输血杂志

【Objective】 To analyze the correlation of HBV serological characteristics between non-reproducible reactivity (NRR) samples and occult hepatitis B virus infection (OBI) samples for blood screening. 【Methods】 A total of 144 samples with negative ELISA (HBV, HCV and HIV test) results and reactive nucleic acid tests(NAT) were collected from January 2021 to January 2023 in Anhui Blood Center, including 92 reactive samples by TMA method (combined ID-NAT) and 52 HBV DNA reactive samples by PCR method (ID-NAT). Supplementary differential testing and ID-NAT by PCR were performed on the reactive samples of the combined ID-NAT, samples that were non-reactive by both differential testing and ID-NAT by PCR were included in the NRR group, and samples that were reactive for HBV DNA detected by either method were included in the OBI group. Supplemented with HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc tests, the differences in serological pattern and positive rate between NRR samples and OBI samples were analyzed. 【Results】 A total of 53 samples were negative for differential testing and ID-NAT and were included in the NRR group, 91 samples were detected as HBV DNA reactive in either method and were included in the OBI group. HBsAg and HBeAg were not detected by serological testing in either group. The detection rates of anti-HBs, anti-HBc and anti-HBe in the NRR group and the OBI group were 64.15% vs 47.25%, 86.79% vs 94.51%, 35.85% vs 52.75%, respectively. Comparison of serological patterns between the two groups: the most frequent pattern in the NRR group was anti-HBs (+ ) and anti-HBc (+ ) (32.08%), and the most frequent pattern in the OBI group was anti-HBe (+ ) and anti-HBc (+ ) (37.36%). 【Conclusion】 There were differences in some of the test results between the NRR samples and the OBI samples in HBV serological testing, and higher anti-HBc positive rate in the NRR samples suggests a higher possibility of HBV infection.

Different Characteristics of Psychological and Sleep Symptoms Across Social Media Addiction and Internet Gaming Disorder in Chinese Adolescents- A Network Analysis

Objective@#Previous research has explored a variety of mental disorders associated with Internet Gaming Disoder (IGD) and Social Media Addiction (SMA). To date, few studies focused on the network characteristics and investigated mood and sleep symptoms across SMA and IGD of adolescence at a group-specific level. This study aims to identify different characteristics of IGD and SMA and further determine the group-specific psychopathology process among adolescents. @*Methods@#We conducted a cross-sectional study to recruit a cohort of 7,246 adolescents who were scored passing the cutoff point of Internet Gaming Disorder Scale-Short Form and Bergen Social Media Addiction Scale, as grouped in IGD and SMA, or otherwise into the control group. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item, and Pittsburgh Sleep Quality Index were assessed for the current study, and all assessed items were investigated using network analysis. @*Results@#Based on the analytical procedure, the participants were divided into three groups, the IGD group (n=789), SMA group (n=713) and control group (n=5,744). The edge weight bootstrapping analysis shows that different groups of networks reach certain accuracy, and the network structures of the three groups are statistically different (pcontrol-IGD=0.004, pcontrol-SMA<0.001, pIGD-SMA<0.001). The core symptom of SMA is “feeling down, depressed, or hopeless”, while IGD is “feeling tired or having little energy”. @*Conclusion@#Although IGD and SMA are both subtypes of internet addiction, the psychopathology processes of IGD and SMA are different. When dealing with IGD and SMA, different symptoms should be addressed.

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.

Expression and significance of N-WASP in placentas with preeclampsia / 中国医科大学学报

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

Application of Two-Dimensional Speckle Tracking Technique to Assess Right Heart Function and Right Ventricle-Pulmonary Artery Coupling in Rheumatoid Arthritis / 中国医学影像学杂志

Purpose To assess the right atrial and right ventricular strain and right ventricular-pulmonary artery(RV-PA)coupling in rheumatoid arthritis(RA)via two-dimensional speckle tracking.Materials and Methods Sixty patients with RA in the General Hospital of Ningxia Medical University from June 2020 to June 2022 were prospectively selected,and all RA patients were divided into three groups according to pulmonary artery systolic pressure(PASP),including group A(n=20 cases)with PASP<33 mmHg,group B(n=20 cases)with PASP 33-39 mmHg as mild ePH,and group C(n=20 cases)PASP≥40 mmHg,twenty healthy individuals were selected as the control group.All subjects underwent transthoracic echocardiography,and right atrial and right ventricular systolic function was assessed by two-dimensional speckle tracking technique,and RV-PA coupling was assessed noninvasively by right ventricular free wall strain/pulmonary artery systolic pressure(RV FWS/PASP),pulmonary function was analyzed by pulmonary function instruments.Spearman's analysis was used to analyze the correlation between right heart function and RV-PA coupling to pulmonary diffusion function.Results There were statistical differences in right ventricular base diameter,right atrium diameter,tricuspid annular plane systolic excursion,inferior vena cava diameter,PASP,right ventricular global strain,RV FWS,right atrium strain-reservoi,right atrium strain-conduit(S-CD),RV FWS/PASP among the four groups(F/H=2.369-74.880,all P<0.05).Right atrium strain-reservoi[(36.0±7.9)%vs.(30.9±7.8)%],right atrium S-CD[(19.9±6.9)%vs.(15.3±4.7)%]and RV FWS/PASP(0.96±0.19 vs.0.56±0.13)in group B were significantly lower than those of group A(t=2.040,2.262,7.704,all P<0.05).There was a good correlation between diffusing capacity of the lung for carbon monoxide single-breathmethod and right ventricular global strain,RV FWS,right atrium S-CD and RV FWS/PASP in RA patients(r=0.392,0.472,0.431,0.572,all P<0.05).Conclusion The more increases of pulmonary artery pressures,the more decreases of right heart function in RA patients,and the more uncoupling in RV-PA.Right heart dysfunction and right ventricle-pulmonary artery uncoupling have developed in RA patients with PASP 33-39 mmHg,with association of pulmonary diffusion dysfunction.

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.

Clinical study on different doses of paricalcitol combined with cinacalcet in the treatment of secondary hyperparathyroidism in patients with maintenance hemodialysis / 中国医师进修杂志

Objective:To investigate the clinical value of different doses of paricalcitol combined with cinacalcet in the treatment of secondary hyperparathyroidism (SHPT) in patients with maintenance hemodialysis (MHD).Methods:The clinical data of 90 patients with MHD combined with SHPT from December 2020 to December 2022 in Beijing Geriatric Hospital were retrospectively analyzed. Among them, 30 patients were treated with cinacalcet (control group), 30 patients were treated with fixed dose paricalcitol combined with cinacalcet (experimental group A), and 30 patients were treated with adjusting dose of paricalcitol based on the level of intact parathyroid hormone (iPTH) combined with cinacalcet (experimental group B). All patients were continuously treated for 8 weeks. The blood calcium, blood phosphorus, iPTH, osteoprotegerin, osteocalcin, type Ⅰ collagen carboxy terminal peptide cross-linking (β-CTX), N-terminal medium molecule fragment of calcium (N-MID), fibroblast growth factor-23 (FGF-23) and Klotho protein before treatment and after 4 and 8 weeks of treatment were detected; coronary artery calcification (CAC) score and abdominal aortic calcification (AAC) score were evaluated. The adverse reactions were recorded.Results:There were no statistical differences in the indexes before treatment among three groups ( P>0.05). There were no statistical differences in blood calcium and blood phosphorus after 4 and 8 weeks of treatment among three groups ( P>0.05). After 4 and 8 weeks of treatment, the iPTH, β-CTX, osteoprotegerin, N-MID, osteocalcin and FGF-23 in experimental group A and experimental group B were significantly lower than those in control group, after 4 weeks of treatment: (936.99 ± 202.36) and (635.74 ± 135.44) ng/L vs. (1 028.56 ± 11.39) ng/L, (1.85 ± 0.32) and (1.50 ± 0.27) μg/L vs. (2.27 ± 0.69) μg/L, (71.18 ± 6.98) and (64.33 ± 7.87) ng/L vs. (80.15 ± 10.85) ng/L, (106.36 ± 14.42) and (92.64 ± 11.32) μg/L vs. (135.19 ± 15.18) μg/L, (66.17 ± 8.52) and (60.21 ± 7.85) μg/L vs. (73.15 ± 9.44) μg/L, (109.17 ± 11.24) and (98.50 ± 10.36) ng/L vs. (126.18 ± 15.64) ng/L; after 8 weeks of treatment: (632.17 ± 154.98) and (526.85 ± 98.45) ng/L vs. (819.85 ± 169.78) ng/L, (1.33 ± 0.15) and (1.15 ± 0.20) μg/L vs. (1.78 ± 0.27) μg/L, (65.78 ± 9.74) and (52.77 ± 7.18) ng/L vs. (74.26 ± 11.58) ng/L, (85.64 ± 11.62) and (70.25 ± 8.59) μg/L vs. (105.92 ± 19.17) μg/L, (48.17 ± 5.99) and (41.15 ± 6.44) μg/L vs. (59.24 ± 6.87) μg/L, (90.15 ± 11.25) and (82.58 ± 9.74) ng/L vs. (105.26 ± 14.35) ng/L, the indexes in experimental group B were significantly lower than those in experimental group A, and there were statistical differences ( P<0.05). After 4 and 8 weeks of treatment, the Klotho protein in experimental group A and experimental group B was significantly higher than that in control group, after 4 weeks of treatment: (124.25 ± 14.85) and (146.31 ± 16.85) U/L vs. (107.26 ± 11.36) U/L, after 8 weeks of treatment: (135.62 ± 16.87) and (150.24 ± 17.43) U/L vs. (115.56 ± 15.48) U/L, the Klotho protein in experimental group B was significantly higher than that in experimental group A, and there were statistical differences ( P<0.05). After 4 and 8 weeks of treatment, the CAC score and AAC score in experimental group A and experimental group B were significantly lower than those in control group, the indexes in experimental group B were significantly lower than those in experimental group A, and there were statistical differences ( P<0.05). There was no statistical difference in the incidence of adverse reactions among three groups ( P>0.05). Conclusions:Compared with the fixed dose of paricalcitol combined with cinacalcet therapy, the adjusting the dosage of paricalcitol combined with cinacalcet therapy based on iPTH level has more definite therapeutic effects in patients with MHD combined with SHPT, which can improve bone metabolism and reduce vascular calcification.

Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity / 药物分析学报

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

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.

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.

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.

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.

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.

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.

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.