Mechanism of Prunellae Spica Against Breast Diseases： A Review / 中国实验方剂学杂志

Prunellae Spica is the dry ear of the labiaceae plant Prunella vulgaris， which is a traditional medicine and food plant with many functions. Prunellae Spica can clear liver-fire， improve eyesight， disperse knot detumescence. It owns hot and bitter flavors and cold property. It goes to the liver， gallbladder meridian， and is a kind of commonly-used antifebric. Prunellae Spica has been used in the treatment of mammary gland diseases since ancient times.The mammary abscess， mammary nodules， mammary carcinoma of traditional Chinese medicine all belong to breast disease， and the liver meridian is most closely related to these diseases. With the development of social life， breast disease has gradually become the most primary health problem for women. Modern pharmacological studies show that Prunellae Spica contains terpenoids， phenolic acids， flavonoids and other biological active components， which have anti-inflammatory， antibacterial， hormone regulation， anti-tumor and other effects. Prunellae Spica inhibits the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） pathway to play an anti-mastitis role， interferes with the effects of estrogen receptors or regulates lipid levels to treat breast hyperplasia， and treats breast cancer through promoting the apoptosis of breast cancer cells， inhibiting the migration of breast cancer cells， regulating the division of breast cancer cells and other ways. While referring to the relevant literature， it was found that Prunellae Spica often exerted pharmacological effects through multi-channels and multi-target regulation， but most of the studies did not specify the specific target of its effect， which needs further study. In this review， the effects and mechanisms of Prunellae Spica in the treatment of various breast diseases were summarized， so as to provide a reference for further research on the wider clinical therapeutic effects of Prunella subtilis and its therapeutic effects on breast diseases.

Effects of parental involvement on children s eye use behavior / 中国学校卫生

Objective@#To analyze the correlation between parental involvement and the formation of good eye use behavior in children,and to provide theoretical basis for more accurate prevention and control of myopia.@*Methods@#A total of 2 726 children and their parents from 3 primary schools were selected from April to May 2021 by clustering sampling method. Children s ocular parameters, eye use behavior, general characteristics of parents, and parental involvement were collected through ocular measurements and questionnaires, respectively.@*Results@#Parental involvement was associated with family economic, parental education level, and parental myopic status( P <0.05). Children s myopia risk was associated with parental involvement: lower myopia risk was associated with frequent parental involvement in behavioral management of child sleep and child outdoor activities( P <0.01). Parents who always/frequently participate in the management of children s eye behavior have an average daily screen time of <2 h ( OR= 1.95 , 95%CI =1.31-2.90), and daily outdoor activity time>2 h ( OR=0.78, 95%CI =0.65-0.93), daily sleep time >8 h ( OR= 0.52 , 95%CI =0.40-0.68), daily continuous reading and writing time <1 h ( OR=1.33, 95%CI =1.30-1.56), reading and writing The distance from the desktop > 30 cm ( OR=0.57, 95%CI =0.34-0.95) had a statistically significant effect ( P <0.05).@*Conclusion@#High parental involvement may help school age children develop good eye habits and reduce the risk of childhood myopia. Parental involvement is higher among those who had myopia themselves, and parental involvement is positively associated with total household income and parental literacy.

A long-term ischemic stroke risk score model in patients aged 60 years and older with obstructive sleep apnea: a multicenter prospective cohort study / 南方医科大学学报

OBJECTIVE@#To analyze the independent risk factors of long-term ischemic stroke and establish a nomogram for predicting the long-term risks in elderly patients with obstructive sleep apnea (OSA).@*METHODS@#This multicenter prospective cohort study was conducted from January, 2015 to October, 2017 among consecutive elderly patients (≥60 years) with newly diagnosed OSA without a history of cardio-cerebrovascular diseases and loss of important clinical indicators. The follow-up outcome was the occurrence of ischemic stroke. The baseline demographic and clinical data, sleep parameters, laboratory and ultrasound results were collected from all the patients, who were randomized into the modeling group (n=856) and validation group (n=258) at a 3∶1 ratio. LASSO regression was used for variable reduction and dimension screening, and the risk score prediction model of ischemic stroke was established based on Cox proportional hazard regression.@*RESULTS@#In the total of 1141 patients enrolled in this study, 58 (5.08%) patients experienced ischemic stroke during the median follow-up of 42 months (range 41-54 months). The cumulative incidence of ischemic stroke was 5.14% in the model group and 4.91% in the verification group (P < 0.05). Age (HR=3.44, 95% CI: 2.38- 7.77), fasting blood glucose (FPG) (HR=2.13, 95% CI: 1.22-3.72), internal diameter of the ascending aorta (HR=2.60, 95% CI: 1.0- 4.47), left atrial anteroposterior diameter (HR=1.98, 95% CI: 1.75-2.25) and minimum oxygen saturation (LSpO2) (HR=1.57, 95% CI: 1.20-1.93) were identified as independent risk factors for ischemic stroke (P < 0.05 or 0.01). A long-term ischemic stroke risk score model was constructed based the regression coefficient ratios of these 5 risk variables. Before and after the application of the Bootstrap method, the AUC of the cohort risk score model was 0.84 (95% CI: 0.78- 0.90) and 0.85 (95% CI: 0.78- 0.89) in the model group and was 0.83 (95% CI: 0.73-0.93) and 0.82 (95%CI: 0.72-0.90) in the verification group, respectively, suggesting a good prediction efficiency and high robustness of the model. At the best clinical cutoff point, the cumulative incidence of ischemic stroke was significantly higher in the high-risk group than in the low-risk group (P=0.021).@*CONCLUSION@#This model can help to identify high-risk OSA patients for early interventions of the risks of ischemic stroke associated with OSA.

Identification of onco-miRNAs in hepatocellular carcinoma and analysis of their regulatory network / 南方医科大学学报

OBJECTIVE@#To construct the regulatory network of survival-related onco-miRNAs and their target genes in hepatocellular carcinoma (HCC) and verify the interactions between the key miRNAs and their targets.@*METHODS@#We screened survival-related miRNAs in HCC in OncomiR and Oncolnc databases, predicted their target genes using miRNet, and conducted survival and expression analysis using GEPIA2 and Ualcan, respectively. The miRNA-target gene co-expression analysis was performed and the miRNA-target network was constructed. Enrichment analysis was performed in Enrichr and protein-protein interaction analysis in STRING database. We tested the effects of transfection with the mimic or inhibitor of hsa-miR-1226-3p or hsa-miR-221-5p on proliferation of HepG2 cells using CCK8 assay and examined the changes in the expressions of the target genes using RT-qPCR. The effect of transfection with hsa-miR-221-5p mimic or inhibitor on protein expressions of the target genes was examined using Western blotting in. A dual luciferase reporter assay was used to test the interaction between hsa-miR-221-5p and its potential target gene GCDH. We further examined the effect of transfection with hsa-miR-221-5p mimic and pEGFP N1-GCDH, alone or in combination, on proliferation, migration and invasion of HepG2 cells.@*RESULTS@#We identified 223 survival-related miRNAs in HCC from OncomiR and 146 miRNAs from Oncolnc with an intersection of 131 miRNAs, and 48 miRNAs were identified as onco-miRNAs in HCC after survival and expression analysis. Twenty-seven eligible target genes were identified after miRNA-mRNA co-expression analysis. The constructed miRNA-target gene network consisted of 25 miRNAs and 27 target genes. The most enriched term was fatty acid metabolism for the target genes. In HepG2 cells, transfection with the mimic or inhibitor of hsa-miR-1226-3p or hsa-miR-221-5p caused significant changes of the mRNA and protein levels of their respective target genes (P < 0.05). The results of dual luciferase reporter assay confirmed the targeting relationship between hsa-miR-221-5p and GCDH gene (P < 0.05). Transfection with hsa-miR-221-5p mimic significantly suppressed the proliferation, migration and invasion of HepG2 cells, but this effect was obviously relieved by co-transformation with pEGFP N1-GCDH (P < 0.05).@*CONCLUSION@#Fatty acid metabolism might be one of the most crucial pathways that mediate the effect of the oncomiRNAs in HCC, and the hsa-miR-221-5p/GCDH axis is an important molecular mechanism for HCC progression.

Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma / 中国医学科学杂志(英文版)

Objective Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis. Methods A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN. Results Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that "Cell Cycle, Mitotic" was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest. Conclusions Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD.

Identification of chemical constituents of Xiaochengqi Decoction by UPLC-Q-TOF/Fast DDA combined with UNIFI software / 中国中药杂志

Based on the combination of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF) and Waters UNIFI software, the chemical constituents of the classic prescription Xiaochengqi Decoction were qualitatively analyzed and identified. The UPLC conditions are as follows: Acquity HSS T3 reverse phase column(2.1 mm ×100 mm, 1.8 μm), column temperature of 30 ℃, mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B), and flow rate of 0.3 mL·min~(-1). High-resolution MS data of Xiaochengqi Decoction were collected in ESI~(+/-) modes by Fast DDA. The structures of the chemical constituents were tentatively characterized or identified by UNIFI software according to the retention time of reference standards and characteristic fragment ions in MS profile, and literature data. A total of 233 components in Xiaochengqi Decoction were identified, with 93 from wine-processed Rhei Radix et Rhizoma, 104 from bran-processed Aurantii Fructus Immaturus, and 36 from ginger-processed Magnoliae Officinalis Cortex. These 233 components included anthraquinones, flavonoids, lignans, alkaloids, coumarins, and phenylethanoid glycosides. The result provided experimental evidence for the further study on establishment of quality standard and product development of the formula.

Analysis of chemical constituents in classical prescription Danggui Buxue Decoction based on RP-Q-TOF-MS and HILIC-Q-TOF-MS / 中国中药杂志

The chemical constituents of classical prescription Danggui Buxue Decoction were analyzed by reversed-phase(RP) chromatography and hydrophilic interaction chromatography(HILIC) coupled with quadrupole time-of-flight mass spectrometry. RP separation of Danggui Buxue Decoction was performed on ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 μm), while HILIC separation was on Waters BEH Amide(2.1 mm×100 mm, 1.7 μm). Mass spectrometry(MS) data were acquired in both negative and positive ion modes. Chemical constituents of Astragali Radix and Angelicae Sinensis Radix were searched from Reaxys and thus the in-house library was established. MS data were further analyzed by MassLynx 4.1 combined with in-house library, HMDB, Reaxys, and comparison with reference substances. In conclusion, a total of 154 compounds were identified and characterized: 16 saponins, 44 flavonoids, 10 phthalides, 7 phenylpropanoids, 15 bases and the corresponding nucleosides, 30 oligosaccharides, and 32 other compounds. Among them, 65 compounds were detected by HILIC-MS/MS. This study provides experimental evidences for the material basis research, quality control, and preparation development of Danggui Buxue Decoction and a reference method for comprehensive characterization of Chinese medicine decoctions typified by classical prescriptions.

Molecular mechanism of Ganoderma against gastric cancer based on network pharmacology and experimental test / 中国中药杂志

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.

The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study

Background/Aims@#Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters. @*Methods@#A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency. @*Results@#The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate. @*Conclusions@#The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

Application value of checklist-based transitional care on patients relatives relocation stress in patients undergoing cardiac surgery / 中国实用护理杂志

Objective:To explore the application value of checklist-based transitional care on patients relatives relocation stress in patients undergoing cardiac surgery.Methods:A total of 92 patients who undergoing cardiac surgery were assigned to experimental group ( n=46) and control group ( n=46). Patients in the control group received routine ICU transitional care, the experiment group carried out checklist-based ICU transitional care. The transfer time, time of early ambulation, length of hospitalization and incidence of postoperative complications were compared between two groups. Meanwhile, the relatives stress levels were assessed by family relocation stress scale. Results:The transfer time, time of early ambulation and post-intensive care syndrome rate were (11.80±3.58) min, (18.65±4.63) min and 4.35% (2/46) in the experimental group, significantly lower than those in the control group [(13.83±3.49)min, (21.37±4.97) min, 17.39% (8/46)], the difference was statistically significant ( t value was 2.739, 2.713, χ2 value was 3.866, P<0.05). After ICU transferring, the scores of preparation for relocation, family burden, satisfaction with the relocation process and total relocation stress were 21.11±2.57, 13.83±2.10, 7.57±1.11 and 7.57±1.11, significantly higher than in the control group (19.65±3.28, 19.65±3.28, 6.76±1.62, 46.43±4.11), the difference was statistically significant ( t value was 9.222-20.187, P<0.05). Conclusions:Checklist-based transitional care can reduce ICU transfer time, decrease postoperative pain and complications in patients undergoing cardiac surgery, which can also alleviate the levels of relatives relocation stress.

Effect of Huanglian Wendantang on Classical Pathway of Skeletal Muscle Pyroptosis in IGT Rats / 中国实验方剂学杂志

Objective:To explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）/IL-18 signaling pathway. Method:The SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg^-1d^-1）， and an HLWDT （7.8 g·kg^-1d^-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg^-1d^-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1<italic>β</italic> and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1<italic>β</italic>， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles. Result:Compared with the blank group， the model group showed increased IL-1<italic>β</italic> and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1<italic>β </italic>protein expression in skeletal muscle tissues of the model group was significantly elevated （<italic>P</italic><0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1<italic>β</italic> and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1<italic>β</italic>， and IL-18 in skeletal muscles of IGT rats （<italic>P</italic><0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats<bold>.</bold> Conclusion:HLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1<italic>β</italic> signaling pathway.

Effect of Guizhitang on Atherosclerosis by Regulating Immune and Intestinal Flora / 中国实验方剂学杂志

Objective:To observe the effect of Guizhitang （GZT） on peripheral blood monocytes， intestinal flora and AS plaque formation of ApoE^-/- mice induced by Western diet （WD）. Method:In this study， 40 12-week-old homozygous female ApoE^-/- mice were randomly divided into chow diet （CD） group （ApoE^-/-+CD）， WD group （ApoE^-/-+WD）， GZT group （ApoE^-/-+WD+GZT， 7.83 g·kg^-1） and atorvastatin （Atr） group （ApoE^-/-+WD+Atr， 3.33 mg·kg^-1）. And 10 matched C57BL/6 mice were set as wild CD control group （C57BL/6+CD）. Except the CD group， the rest groups were given WD to induce models. Treatment groups were given Guizhitang or atorvastatin orally in addition to WD， while ApoE^-/-+CD and ApoE^-/-+WD model groups were treated with the same volume of double steam water at the same time. After 4 weeks of intervention， 5 mice in each group were selected to collect the eyeball blood samples. The levels of plasma lipids were detected by automatic biochemical analyzer， and the proportion of peripheral blood mononuclear cells and its subtypes， and the expression levels of surface receptors toll like receptor 4 （TLR4） and CD36 were detected by flow cytometry， the intestinal flora of mice was detected by 16S rDNA sequencing. The remaining 5 mice in each group were intervened for 12 weeks， and the aorta was taken to detect the formation of aortic plaque by oil red O staining. Result:After intervention for 4 week， compared with C57BL/6+CD group， the levels of plasma total cholesterol （TC） and low-density lipoprotein （LDL） levels in ApoE^-/-+CD and ApoE^-/-+WD groups were increased （<italic>P</italic><0.01）. ApoE^-/-+WD group showed increase in the proportion of monocytes， their inflammatory subtypes Ly6C^__， and TLR4 expression on monocyte surface in blood （<italic>P</italic><0.05）. ApoE^-/-+WD group induced the imbalance of intestinal flora， with increase of Firmicutes and decrease of Verrucomicrobia in ileum of ApoE^-/-mice. Compared with ApoE^-/-+WD group， there was no significant change in blood lipid level and monocyte proportion in ApoE^-/-+WD+GZT group， but with decrease in the proportion of Ly6C^__， increase in the proportion of anti-inflammatory subtype Ly6C^-， and decrease in the expression of TLR4 and CD36 on monocyte surface （P<0.05）. ApoE^-/-+WD+GZT group showed decrease of Firmicutes and increase of Bacteroidetes and Verrucomicrobia in ileum of ApoE^-/-mice. After 12 weeks of intervention， ApoE^-/-+WD group showed increase in the number and area of aortic plaques in ApoE^-/-mice. ApoE^-/-+WD+GZT group showed decrease of the area of aortic AS plaques. Conclusion:GZT can reduce the immune damage and imbalance of intestinal flora caused by WD， then inhibit the formation of AS plaque.

The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65

Background@#Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. @*Methods@#Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. @*Results@#The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. @*Conclusion@#The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65

Background@#Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. @*Methods@#Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. @*Results@#The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. @*Conclusion@#The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Clinical significance of CD34 / 医学前沿

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34

Mechanism of Huanglian Wendan Decoction in improving impaired glucose tolerance based on skeletal muscle NLRP3/caspase-1/IL-1β, IL-18 pathway / 中国中药杂志

This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1β(IL-1β), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1β and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1β, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.

Comparison of in vivo pharmacokinetics of five constituents in Zhishi Zhizi Chi Decoction in normal rats and CUMS-induced depressive rats / 中国中药杂志

A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-β-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-β-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)μg·L~(-1)and AUC_(0-t)(612.56±148.50)μg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)μg·L~(-1)and AUC_(0-t)(413.14±76.37)μg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)μg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)μg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)μg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)μg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)μg·L~(-1),and AUC_(0-t)(608.62±289.05)μg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)μg·L~(-1),and AUC_(0-t)(501.07±242.68)μg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)μg·L~(-1)and AUC_(0-t)(141.19±54.63)μg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)μg·L~(-1)and AUC_(0-t)(69.51±14.73)μg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)μg·L~(-1)and AUC_(0-t)(1 292.29±553.73)μg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)μg·L~(-1)and AUC_(0-t)(385.99±138.55)μg·L~(-1)·h for the normal group.

Research progress on determination of intracellular concentration of immunosuppressant / 器官移植

Currently, extracellular concentration measurement is the major approach of therapeutic drug monitoring (TDM) of clinical immunosuppressant in organ transplantation. Its correlation with the efficacy of immunosuppressant remains elusive. With widespread application of liquid chromatography, the detection technology of intracellular concentration of immunosuppressant is gradually mature. Theoretically, it may more accurately reflect the efficacy of immunosuppressant due to that the level of drug exposure in target cells can be directly measured. In this article, the history and present situation of the determination of intracellular concentration of immunosuppressant were summarized, and the association between the determination methods of intracellular concentration of immunosuppressant and drug efficacy was emphatically analyzed. Detection of intracellular concentration of immunosuppressant possesses better application value in clinical practice, which is worthy of promotion in clinical settings.

Effect of daily average temperature on the incidence of allergic rhinitis in Lanzhou / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the effect of daily average temperature on the atteck of allergic rhinitis (AR) by analyzing the changes of the outpatient visits of AR in Lanzhou. Methods: The meteorological and air pollution data of Lanzhou City and the outpatient visits of AR in Departments of Otorhinolaryngology and head and neck surgery of The First Hospital of Lanzhou University, The Second Hospital of Lanzhou University and Gansu Provincial People's Hospital from 2013 to 2017 were collected to describe the meteorological factors, air pollutants and the outpatient visits of AR. The correlation among the three factors was then analyzed by Spearman rank correlation analysis. Using the distributed lag non-linear model, the relationship between daily average temperature and the number of daily outpatient visits of AR was studied and stratified by gender and age with the long-term trend, seasonal trend and other confounding factors controlled. Results: From 2013 to 2017, the outpatient visits of AR in the above three hospitals reached 20 008 person times. Daily average temperature in Lanzhou showed a non-linear correlation to the outpatient visits of AR, with a certain lag effect. When the daily average temperature was 22 ℃ and the cumulative lag was 21 days (lag 0-21 d), the relative risk (RR) peaked at 4.851 (95%CI: 3.986-5.904). The effect of relatively low temperature (2.3 ℃, P25), relatively high temperature (19.8 ℃, P75) and high temperature (25.5 ℃, P95) on lag 0-21 d were the highest, which were 1.761 (95%CI: 1.375-2.255), 4.299 (95%CI: 3.574-5.171) and 3.656 (95%CI: 3.046-4.389), respectively. According to the stratified analysis, low and relatively low temperature had more significant effect on the outpatient visits of AR among women and people aged 0-14 years. When lag was 0-21 days, the RR value of low temperature for female outpatient visits of AR was 1.433 (95%CI: 1.105-1.860); the RR value of relatively low temperature for female outpatient visits of AR was 1.879 (95%CI: 1.460-2.419); the RR value of low temperature for AR outpatient visits for people aged 0-14 years was 1.511 (95%CI: 0.999-2.287), the RR value of relatively low temperature for AR outpatient visits for people aged 0-14 years was 2.051 (95%CI: 1.383-3.042). Relatively high temperature, on the other hand, had a more significant effect on men and people aged 15-59 years. High temperature had a greater impact on the number of AR outpatients in men and people aged 0-14 years. Conclusions: Temperature may be an important influencing factor of AR onset in Lanzhou. At relatively high temperature (19.8 ℃), the risk of AR outpatient visits is significantly increased, and the cumulative lagged effects are observed. The sensitivity of AR patients to temperature is different in different genders and ages.

Variation analysis of genes associated with Usher syndrome type 1 in 136 Chinese deafness families / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1(MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A, and c.155_166del, c.4802delA of CDH23. The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.