Research and practice of medical laboratory applied talent training program in local colleges and universities / 中华医学教育探索杂志

Objective:To analyze the implementation effects of a medical laboratory talent training program based on local colleges and universities' applied talent-oriented cultivation principal as well as students' interests and industry needs.Methods:Based on the design principals of clarifying the professional orientation, meeting the national standard, reconstructing the curriculum system, introducing the spirit of innovation and entrepreneurship, and multi-dimensional collaborative education, as well as the reverse design path of the outcome-based education concept, we have built a medical laboratory applied talent training system focusing on humanity education, solid foundation, broad employment, and good competency and in accordance with the "three complete education" strategy, along with measures including creating an applied teaching atmosphere, developing an applied curriculum teaching model, providing vocational guidance and improving vocational identity, and promoting education via evaluation. The system was applied to the training and practice of students of grades 2021 and 2022 majoring in medical laboratory technology. SPSS20.0 software was used for statistical analysis.Results:With the concept of application-oriented talent training and the "four-in-one" practical teaching model, students' skills were improved, and the training path was broadened. Compared with those trained with the original program (grades 2019-2020), the graduates trained with the new program (grades 2021-2022) showed a significantly decreased employment rate in medical laboratory jobs in medical institutions from 71.25% to 42.86% ( χ2=12.36, P<0.001), a significantly increased employment rate in in-vitro diagnostics industry from 3.75% to 17.14% ( χ2=7.44, P<0.05), and a significantly increased rate of applying for postgraduate education from 17.05% to 32.86% ( χ2=4.74, P<0.05). Conclusions:The medical laboratory talent training program based on the talent training principal of local colleges and universities combined with students' interests and industry needs can help improve the quality of talent training and broaden the employment path of graduates.

The Influence of Late Pregnancy Perineal Massage Combined with Hip Training on Labor Outcomes and Psychological Elasticity of Primiparous Pregnant Women / 实用医学杂志

Objective To investigate the effects of perineal massage combined with hip joint exercise on the outcome of delivery and mental resilience of primipara.Methods 90 pregnant women in the third trimester(after 36 weeks)who obtained the knowledge about perineal massage from midwife clinic were randomly divided into two groups with 45 cases each.The control group received regular antenatal examination and family self-exercise;the experimental group received perineal massage and hip joint training combined treatment.The delivery outcome,birth experience and maternal mental resilience of the two groups were compared.Results the number of vaginal delivery in the experimental group were higher than that in the control group(P<0.05);the second stage of labor was significantly shorter than that of the control group(P<0.05);the perineal integrity rate was higher than that of the control group(P<0.05);the scores of all dimensions in delivery experience questionnaire were higher than that of the control group(P<0.05);the scores of all dimensions in maternal mental resilience were higher than those of the control group(P<0.05)after intervention.Conclusion The perineal massage which conducted by midwives combined with hip movement can effectively improve the quality of delivery,relieve the negative emotions of pregnant women,improve the psychological elasticity level of pregnant women,and improve the delivery outcomes.

Effect of the protein kinase RNA-like endoplasmic reticulum kinase pathway in endoplasmic reticulum stress on hepatic stellate cell activation and collagen type I expression / 临床肝胆病杂志

ObjectiveTo investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic initiation factor 2α （eIF2α） pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells （HSC）. MethodsPathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis （S1-S4） and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy， and immunohistochemistry was used to measure the protein expression levels of PERK， eIF2α， and C/EBP homologous protein （CHOP）. Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin （0， 125， 250， 500， and 1 000 nmol/L）， and qRT-PCR was used to measure the mRNA expression level of PERK， while Western blot was used to measure the protein expression levels of PERK， inositol requiring protein 1 （IRE1）， activating transcription factor 6 （ATF6）， CHOP， and α-smooth muscle actin （α-SMA）. The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group； qRT-PCR was used to measure the mRNA expression levels of PERK， eIF2α， and α-SMA， Western blot was used to measure the protein expression levels of PERK， phosphorylated eIF2α （p-eIF2α）， and α-SMA， and immunofluorescence assay was used to measure the expression of collagen type I alpha 1 （COL1A1）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with normal liver tissue， the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK， eIF2α， and CHOP （Z=-3.56， t=-5.75， Z=-3.52， all P<0.001）. Compared with the solvent group， the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK， CHOP， IRE1， ATF6， and α-SMA （all P<0.05）. Compared with the control group， the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK， eIF2α， and α-SMA and the protein expression levels of PERK， p-eIF2α， and α-SMA （all P<0.05）， and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group （P<0.05）. ConclusionPERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells， suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.

Difference analysis of ADE signal for irinotecan in adults and children / 中国药房

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Difference analysis of ADE signal for irinotecan in adults and children / 中国药房

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Study of the effect of PU-H71 on increasing radiosensitivity of cervical cancer cells / 中华放射肿瘤学杂志

Objective:To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells.Methods:The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results:PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair.Conclusion:PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Analysis of related factors of emotional and behavioral abnormalities in children with overactivity of bladder / 现代泌尿外科杂志

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Development of a perineal pain management scheme after vaginal delivery based on integrated maternity and childbirth / 现代临床护理

Objective To propose an integrated management scheme for perineal pain after vaginal delivery.Methods Literature review and Delphi inquiry were conducted to propose the perineal pain management scheme after vaginal delivery from November 2022 to April 2023.A total of 21 experts were consulted with 2 rounds of correspondence.Results Questionnaires collected from the two rounds of correspondence consultations were both at 100.0%.The expert authority coefficients for the two rounds were 0.930 and 0.935,respectively,with the expert coordination coefficients of the two rounds at 0.109(P<0.001)and 0.392(P<0.001),full mark rate 100%.A total of 3 primary items,15 secondary items and 40 tertiary items were summarised for the perineal pain management scheme after vaginal delivery in relation to prenatal prophylaxis,intrapartum protection and postnatal treatment.Conclusions The developed perineal pain management scheme after vaginal delivery is scientific and reliable.It provides a scientific reference for the prevention and treatment of perineal pain after vaginal delivery.

Study on molecular mechanism Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma in the treatment of ulcerative colitis based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To investigate the pharmacological effects and molecular mechanisms of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma for the treatment of ulcerative colitis based on the network pharmacology and molecular docking methods.Methods:TCMSP database was applied to get the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma, and SwissTargetPrediction database was applied to predict their targets; OMIM, DrugBank, TTD, PharmGKB and GeneCards databases were used to obtain the disease targets of ulcerative colitis; Venn Diagram website was used to draw the venn diagrams of drug-disease intersecting targets; drug-component-target network diagrams were created in Cytoscape 3.8.2, and the targets and active components with high correlation in the network were analyzed; protein interaction networks of intersecting targets were constructed using the String platform, and the NetworkAnalyzer plug-in in Cytoscape 3.8.2 was applied to Topology analysis and screening of core targets were performed using the Metascape platform; GO and KEGG analysis were performed using the Metascape platform; molecular docking validation was performed using vina inside pyrx software.Results:A total of 14 active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma were screened, and the core components were kaempferol, stigmasterol, hederagenin, α-amyrin; 148 drug targets, 1 307 disease targets and 50 drug-disease intersection targets were obtained; there were 23 core points such as ESR1, PTPN2, PIK3R1, SRC, EGFR, and AKT1. The results of GO analysis indicated that the targets were mainly located in the cell membrane region and were involved in the regulation of biological functions such as monooxygenase and oxidoreductase activities, as well as the regulation of hormones and lipids, etc. The results of KEGG pathway enrichment analysis revealed that the main enrichment pathways were PI3K-Akt, JAK-STAT and MAPK signaling pathways. The molecular docking results showed that the main components, kaempferol and serpentine, could bind stably to several core targets such as PIK3R1 and ESR1. Relevant literature has verified the pharmacological action of each core component.Conclusions:Kaempferol, hederagenin and α-amyrin are the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma. They play therapeutic roles in improving immune dysregulation, reducing inflammatory response, inhibiting epithelial cell apoptosis and repairing mucosal damage by regulating targets such as PIK3R1, PTPN2 and ESR1, and modulating PI3K-Akt pathway, JAK-STAT pathway and MAPK pathway.

Study on network pharmacology and molecular docking of Shenling Baizhu Powder for treating different diseases with same method on type 2 diabetes mellitus and ulcerative colitis / 国际中医中药杂志

Objective:To discuss the molecular association pattern of Shenling Baizhu Powder for type 2 diabetes (T2DM) and ulcerative colitis through network pharmacology method based on the theory of "treating different diseases with same method" in TCM.Methods:The TCMSP and ETCM Chinese medicine chemical composition databases were used to obtain the chemical composition and predict the targets of Shenling Baizhu Powder. The OMIM, GeneCards, DrugBank and TTD disease databases were used to obtain the disease targets of T2DM and ulcerative colitis. The intersection targets of chemical composition of Shenling Baizhu Powder, T2DM and ulcerative colitis were obtained by Bioinformatics platform. Cytoscape 3.8.2 software was used to map the "Chinese materia medica-component-target" network and "effective component- intersection target" network. The GO enrichment analysis and KEGG pathway analysis of the intersection targets were performed with the STRING platform. The intersection target protein-protein interaction network was constructed by STRING database, and core targets were obtained using the CytoNCA plugin of Cytoscape 3.8.2 software. AutodockTools software was applied to validate the molecular docking between the core chemical components and the core targets of Shenling Baizhu Powder.Results:Totally 176 chemical components of Shenling Baizhu Powder, 226 corresponding targets, 11 478 T2DM targets, 4 857 Ulcerative targets of ulcerative colitis, and 162 intersection targets of medicinal chemistry components and diseases were obtained. 1 789 related biological processes, 163 molecular functions, 92 cell constituents, and 192 signaling pathways were obtained by GO enrichment analysis and KEGG pathway analysis. The signaling pathways were mainly about AGE-RAGE, TNF, IL-17,MAPK, PI3K-Akt signaling pathways, etc. The core components of Shenling Baizhu Powder were mainly sitosterol, luteolin, kaempferol, naringenin, beta-carotene, etc. The core targets were EGFR, ALB, IL1B, CASP3, ESR1, VEGFA, PTGS2, TNF, IL6, MYC, AKT 1, JUN, TP53, etc. The core chemical components had tight correlation with the core targets by the molecular docking.Conclusions:By acting on core targets such as TNF, IL1B, IL6, AKT1, VRGFA, PTGS2, MYC, JUN, TP53, and regulating IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, etc., Shenling Baizhu Powder improves tissue inflammation damage, mucosal barrier damage, immune regulation imbalance, intestinal flora dysbiosis, insulin resistance, apoptosis, oxidative stress and other biological processes. Therefore Shenling Baizhu Powder can treat T2DM and ulcerative colitis with the same method.

GID complex regulates the differentiation of neural stem cells by destabilizing TET2 / 医学前沿

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma / 医学前沿

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

A near-infrared spectroscopy study of brain resting state functional connectivity features of frontotemporal lobes in children with autism spectrum disorder / 中国神经精神疾病杂志

Objective To explore the features of frontotemporal lobes'resting-state functional connectivity(rsFC)in preschool children with autism spectrum disorders(ASD)based on functional near-infrared spectroscopy(fNIRS)and to explore the possible neurological markers for early identification of ASD.Methods Sixty-three preschool ASD children and 72 typical development(TD)children were enrolled.Selected bilateral dorsolateral prefrontal cortex(DLPFC),bilateral premotor cortex(PMC),and bilateral temporal lobe(TL)cortex as the regions of interest(ROI).Changes of Oxyhemoglobin in the 6 ROIs in resting-state were measured by using functional near-infrared spectroscopy(fNIRS).Compared the frontotemporal rsFC strength and calculate the laterality index(LI)between two groups.Results Compared with the TD group,rsFC strength was significantly lower in the ASD group(P<0.05),and the differences existed mainly within the left ROIs(0.21±0.11 vs.0.32±0.18),right ROIs(0.16±0.16 vs.0.30±0.14),bilateral DLPFCs(0.20±0.14 vs.0.39±0.17;0.15±0.13 vs.0.36±0.13),bilateral TLs(0.15±0.14 vs.0.28±0.17;0.14±0.15 vs.0.31±0.17),and between the 10 groups of ROIs-ROIs(including right DLPFC-left DLPFC,right DLPFC-right PMC,right DLPFC-left PMC,right DLPFC-right TL,right DLPFC-left TL,left DLPFC-right PMC,left DLPFC-left PMC,left DLPFC-right TL,left DLPFC-left TL,right TL-left TL).There were a significant differences in the rsFC's laterality index of DLPFC and whole-brain between the two groups(t=2.002,P=0.047;t=3.003,P=0.003),and the ASD group showed left-lateralized connectivity.Conclusion Frontotemporal lobe's resting-state functional connectivity is abnormal in preschool children with ASD,characterized by low short-range functional connectivity of bilateral DLPFCs and TLs,low long-range functional connectivity associated with DLPFCs,and left-lateralized connectivity.

The effects of greenness exposure on hypertension incidence among Chinese oldest-old: a prospective cohort study.

BACKGROUND: Although the oldest-old (those aged over 80 years) are vulnerable to environmental factors and have the highest prevalence of hypertension, studies focusing on greenness exposure and the development of hypertension among them are insufficient. The aim of this study was to explore the association between residential greenness and hypertension in the oldest-old population. METHODS: This cohort study included data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The oldest-old were free of hypertension at baseline (2008), and hypertension events were assessed by follow-up surveys in 2011, 2014, and 2018. The one-year averages of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) at 500-m buffer before the interview year of incident hypertension or last censoring interview were collected at the level of 652 residential units (district or county). The linear or nonlinear association between greenness and hypertension incidence was analyzed using the Cox proportional hazards model with penalized splines. The linear links between greenness and hypertension incidence were determined using the Cox proportional hazards model included a random effect term. RESULTS: Among 5253 participants, the incidence rate of hypertension was 7.25 (95% confidence interval [CI]: 6.83-7.67) per 100 person-years. We found a nonlinear association between greenness exposure and hypertension risk, and the exposure-response curve showed that 1 change point existed. We examined the linear effect of greenness on hypertension by categorizing the NDVI/EVI into low and high-level exposure areas according to the change point. We found more notable protective effects of each 0.1-unit increase in greenness on hypertension incidence for participants living in the high-level greenness areas (hazard ratio (HR) = 0.60; 95% CI: 0.53-0.70 for NDVI; HR = 0.46; 95% CI: 0.37-0.57 for EVI). In contrast, no significant influence of greenness exposure on hypertension risk was found for participants living in the low-level greenness areas (HR = 0.77; 95% CI: 0.38-1.55 for NDVI; HR = 0.73; 95% CI: 0.33-1.63 for EVI). CONCLUSIONS: Greenness exposure is nonlinearly associated with hypertension risk among the oldest-old, presenting its relationship in an inverse "U-shaped" curve. Greenness is a protective factor that decreases the risk of hypertension.

Role of LXRα/SREBP-1c in arsenic induced lipid metabolism disorders in rats / 中华地方病学杂志

Objective:To investigate the role of liver X-activated receptor (LXRα)/sterol-regulatory element binding protein (SREBP-1c) in arsenic induced lipid metabolism disorders in rats, and to provide a basis for study the mechanism of arsenic induced lipid metabolism disorders.Methods:Twenty-four healthy clean grade Wistar rats, were randomly divided into 4 groups according to body weight (80 - 100 g) by the random number table method, with 6 rats in each group, half male and half female. Rats in control group were given deionized water by gavage. The low, medium and high arsenic dose groups were given 2.5, 5.0 and 10.0 mg·kg -1·d -1 sodium arsenite solution by gavage, respectively. They were exposed to arsenic for 6 days a week for 4 months. At the end of the experiment, blood and liver samples of rats in each group were collected. The hepatic arsenic content was determined by inductively coupled plasma mass spectrometry (ICP-MS); the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by automatic biochemical analyzer. The mRNA expression levels of LXRα and SREBP-1c in liver tissues were determined by real-time PCR; the protein expression levels of LXRα, SREBP-1c, acetyl CoA carboxylase (ACC) and phospho-ACC (pACC) in liver tissues were determined by Western blotting. Results:The hepatic arsenic contents of rats in low, medium and high arsenic dose groups were (61.04 ± 4.98), (62.66 ± 6.71) and (87.86 ± 13.89) μg/g, respectively, which were higher than that in control group [(2.43 ± 0.63) μg/g, P < 0.05], and the hepatic arsenic content of rats in high arsenic dose group was higher than those in low and medium arsenic dose groups ( P < 0.05). The serum TG levels of rats in low, medium and high arsenic dose groups were (0.90 ± 0.17), (1.28 ± 0.24) and (1.82 ± 0.18) mmol/L, respectively, which were higher than that in control group [(0.50 ± 0.12) mmol/L, P < 0.05]; the serum LDL-C levels of rats in low, medium and high arsenic dose groups were (0.54 ± 0.04), (0.63 ± 0.07) and (0.69 ± 0.08) mmol/L, respectively, which were higher than that in control group [(0.27 ± 0.05) mmol/L, P < 0.05]; the serum TC levels of rats in medium and high arsenic dose groups were (1.88 ± 0.23) and (2.10 ± 0.10) mmol/L, respectively, which were higher than that in control group [(1.51 ± 0.14) mmol/L, P < 0.05]; the serum HDL-C levels of rats in medium and high arsenic dose groups were (0.84 ± 0.11) and (0.71 ± 0.14) mmol/L, respectively, which were lower than that in control group [(1.15 ± 0.08) mmol/L, P < 0.05]; and the serum levels of TG and LDL-C in medium and high arsenic dose groups were higher than those in low arsenic dose group ( P < 0.05), and the serum level of TG in high arsenic dose group was higher than that in medium arsenic dose group ( P < 0.05). The mRNA expression level of hepatic LXRα of rats in high arsenic dose group was higher than those in control group and low arsenic dose group ( P < 0.05); there was no significant difference in mRNA expression levels of hepatic SREBP-1c of rats between low, medium and high arsenic dose groups and control group ( P > 0.05). The protein expression levels of hepatic LXRα of rats in medium and high arsenic dose groups were higher than that in control group ( P < 0.05), and high arsenic dose group was higher than low arsenic dose group ( P < 0.05); the protein expression levels of hepatic SREBP-1c and ACC of rats in high arsenic dose group were higher than that in control group ( P < 0.05). There was a positive correlation between hepatic arsenic content in arsenic-exposed rats and the serum levels of TG, TC, LDL-C, the mRNA expression level of hepatic LXRα, the protein expression levels of hepatic LXRα, SREBP-1c and ACC ( r = 0.84, 0.62, 0.89, 0.55, 0.54, 0.64, 0.70, P < 0.05), and the serum level of HDL-C was negatively correlated with the hepatic arsenic content in arsenic-exposed rats ( r = - 0.75, P < 0.001). Conclusion:Sodium arsenite can increase the serum levels of TG, TC and LDL-C, decrease the serum level of HDL-C and increase the protein expression levels of LXRα and SREBP-1c in liver tissues, suggesting that arsenic induced lipid metabolism disorders in rats may be related to the upstream regulation mechanism of LXRα/SREBP-1c.

Effects of Ginkgo biloba on arsenic-induced lung injury in rats based on HMGB1/RAGE pathway / 中华地方病学杂志

Objective:To investigate the antagonistic and therapeutic effects of Ginkgo biloba on arsenic-induced lung injury in rats and its mechanism.Methods:A total of 42 healthy clean grade Wistar rats, half male and half female, weighing 120 - 130 g, were randomly divided into 7 groups with 6 rats in each group. Two intervention models of Ginkgo biloba antagonism and treatment were established, respectively. The specific treatments were as follows: (1) Experimental study on the antagonism of Ginkgo biloba (4 groups): the control A group was given deionized water; the Ginkgo biloba control (GBE) group was given Ginkgo biloba solution (50 mg·kg -1·bw); the arsenic-treated (As) group was given sodium arsenite solution (10 mg·kg -1·bw); the Ginkgo biloba antagonistic (As + GBE) group was treated with sodium arsenite solution (10 mg·kg -1·bw) and Ginkgo biloba solution (50 mg·kg -1·bw), and the above administration was by gavage for 6 days/week, for 4 months. (2) Experimental study on the treatment of Ginkgo biloba (3 groups): the control B group was given deionized water for 5.5 months; in the arsenism natural recovery (recovery) group, sodium arsenite solution (10 mg·kg -1·bw) was administered by gavage for 4.0 months and deionized water for 1.5 months; the Ginkgo biloba treatment (treatment) group was given sodium arsenite solution (10 mg·kg -1·bw) by gavage for 4.0 months and Ginkgo biloba solution (50 mg·kg -1·bw) for 1.5 months, and the above administration was for 6 days/week. Masson staining was used to evaluate collagen fiber deposition in lung tissue. Western blotting was used to detect the expression level of related proteins in lung tissue homogenates, including inflammatory cytokines matrix metalloproteinase-9 (MMP-9), interleukin (IL)-1β, IL-18; high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) of the HMGB1/RAGE pathway; phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT) of the PI3K/AKT pathway; transforming growth factor (TGF)-β1, SMAD2, p-SMAD2, SMAD3, p-SMAD3 and SMAD4 of the TGF-β1/SMAD pathway. Results:(1) Antagonistic effect of Ginkgo biloba: compared with the control A group, there was no significant change in protein expression and collagen fiber deposition in the lung tissue of GBE group ( P > 0.05); the levels of MMP-9, IL-1β and IL-18 protein expression and collagen fiber deposition in the lung tissue of As group were significantly increased ( P < 0.05); and the levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression were significantly increased ( P < 0.05). Compared with As group, the levels of MMP-9, IL-1β and IL-18 protein expression and collagen fiber deposition were significantly decreased in As + GBE group ( P < 0.05); and levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, and p-SMAD3 protein expression were significantly decreased ( P < 0.05). (2) Therapeutic effect of Ginkgo biloba: compared with control B group, the levels of MMP-9, IL-1β, IL-18 protein expression and collagen fiber deposition were significantly increased in recovery group ( P < 0.05); and the levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression were significantly increased ( P < 0.05). Compared with recovery group, the levels of MMP-9, IL-1β, IL-18, HMGB1, RAGE, PI3K and p-AKT protein expression were significantly decreased in treatment group ( P < 0.05); and there was no significant change in collagen fiber deposition and TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression levels in lung tissue ( P > 0.05). In both experiments, there was no significant difference in the protein expression levels of AKT, SMAD2 and SMAD3 between the groups ( P > 0.05). Conclusion:Ginkgo biloba intervention has ameliorated inflammatory injury and collagen fiber deposition in lung tissue of arsenic-treated rats possibly by inhibiting the expression levels of HMGB1/RAGE pathway-related proteins.

Evidence-based practice of the puncture management in hemodialysis patients with difficult new arteriovenous fistula / 中国实用护理杂志

Objective:To explore the puncture management in hemodialysis patients with difficult new arteriovenous fistula based on the finest evidence-based best practice evidence and evaluate the clinical effects.Methods:A team was formed, according to theoretical framework basing on the evidence of continuous quality improvement model, the best evidence-based interventions were obtained by adopting evidence-based practice. Formulated review indicators, evaluated obstacles and promoting factors in the process of practice, and took corresponding action strategies. From February 2020 to June 2020, 30 patients admitted to the dialysis center of Sir Run Run Shaw Hospital of Zhejiang University were recruited in the baseline review group by convenience sampling method. From September 2020 to January 2021, 30 patients from September 2020 to January 2021 were recruited in the after-effect evaluation group. The baseline review group adopted the original difficult new arteriovenous fistula puncture management scheme, and the after-effect evaluation group adopted the difficult autologous new internal fistula puncture management scheme based on the best evidence. The success rate of one puncture of fistula, the incidence rate of hematoma during puncture and dialysis, the incidence rate of discontinuation of treatment and the compliance with examination indexes were compared in the patients before and after applying for the evidences.Results:Compared with the baseline review group, the success rate of one-time puncture of internal fistula in the aftereffect evaluation group increased from 36.7% (11/30) to 73.3% (22/30), the incidence rate of hematoma during puncture and dialysis were decreased from 33.3%(10/30) to 6.67%(2/30) and 40%(12/30) to 0, the incidence rate of discontinuation of treatment were decreased from 40%(12/30) to3.33% (1/30), the difference was statistically significant ( χ2 values were 6.67-11.88, P<0.05). The implementation rate of review indexes in the aftereffect evaluation group was higher than that in the baseline review group, and the difference was statistically significant ( P<0.05). Conclusions:Evidence-based practice can improve the success rate of difficult new arteriovenous fistula, and reduce the incidence of arteriovenous fistula hematoma, reduce treatment interruption, and better maintain the lifeline of patients.

Focus on multimorbidity in arsenicosis, deepen study and prevention strategies in new era / 中华地方病学杂志

With the aging and lifestyle changes of the residents in arsenicosis area, the disease spectrum has also undergone significant changes, and coexistence of chronic diseases in arsenicosis has become a primary threat to residents health. In the future, basic study from a new perspective should be deepen, to explore new pathways for integrated prevention and treatment of chronic diseases of arsenicosis, and build a whole management model of "screening, management, prevention, treatment and study" to guarantee the prevention and treatment of chronic diseases of arsenicosis.