Effects of occupational radiation exposure on peripheral blood lymphocyte count and cell cycle in logging workers / 中国辐射卫生

Objective To investigate the effects of prolonged low-dose neutron-γ radiation on peripheral blood lymphocytes of logging workers. Methods The health information of workers in a logging company was collected by on-site blood sample collection and questionnaire survey. Individual doses of γ and neutron radiation were recorded using LiF elements and CR-39, respectively. Lymphocyte count in peripheral blood was measured by blood cytometer. Cell cycle and cyclins were detected by flow cytometry. Results The annual dose of some logging workers exceeded 5 mSv. Lymphocyte counts showed a difference of 15% between the group exposed to the lowest annual dose of 0–1 mSv (mean: 2.45 × 109/L) and the group exposed to the highest annual dose of 5–25 mSv (mean: 2.08 × 109/L). In comparison to pre-shift workers, logging workers exhibited a G1-phase arrest in the lymphocyte cycle, along with increased expression of cyclins p21 and CDK2. Conclusion Prolonged exposure to low-dose neutron-γ radiation leads to reduced lymphocyte counts as well as changes in lymphocyte cycle and cyclin expression.

Efficacy of the enhanced recovery after surgery approach in endometrial cancer patients treated with surgical staging and its influence on the oxidative stress response / 中华老年医学杂志

Objective:To analyze the efficacy of the enhanced recovery after surgery(ERAS)approach in endometrial cancer patients treated with surgical staging and its beneficial effects on the oxidative stress response.Methods:Eight-two endometrial cancer patients treated with surgical staging at our hospital between March 2020 and March 2022 were recruited and divided into different groups using a computer-generated random number table, with 41 in the control group who were given routine intervention and 41 in the observation group receiving ERAS.Results:About perioperative performances, the oxidative stress response, inflammatory factor levels and complications were compared between the two groups.Results in the observation group, the intraoperative body surface temperature was higher than in the control group[(36.71±0.22)℃ vs.(36.20±0.21)℃, t=10.737, P=0.000], and the time from the end of surgery to first water intake[(4.41±1.30)h vs.(6.79±1.28)h, t=8.353, P=0.000], to first food intake[(7.86±1.35)h vs.(12.88±2.57)h, t=11.073, P=0.000], to first ambulation[(12.92±3.11)h vs.(24.24±5.06)h, t=12.204, P=0.000], to first flatus[(24.11±4.96)h vs.(35.13±6.20)h, t=8.887, P=0.000], to first bowel movement[(2.67±0.63)d vs.(4.03±1.15)d, t=6.641, P=0.000]and the length of hospitalization[(3.31±1.25)d vs.(5.77±1.59)d, t=7.788, P=0.000]were shorter than in the control group.On the third day after surgery, the levels of malondialdehyde[(77.96±7.62)μmol/L vs.(90.16±7.88)μmol/L, t=7.126, P=0.000], advanced oxidation protein products[(33.16±4.75)μmol/L vs.(43.55±5.37)μmol/L, t=9.280, P=0.000], CAT[(22.59±3.01)U/ml vs.(25.12±3.3)U/ml, t=3.609, P=0.000]and reactive oxygen species[(74.13±5.02)pmol/L vs.(90.33±5.89)pmol/L, t=13.404, P=0.000]in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same time points after surgery.On the 3rd day after surgery, the levels of Tumor Necrosis Factor-α, C-reactive protein and interleukin 6 in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same points after surgery(all P<0.05). In the observation group, the incidence of complications was 14.63%, lower than 39.02% in the control group( χ2=6.212, P=0.013). Conclusions:The ERAS approach can achieve significant results in endometrial cancer patients treated with surgical staging.It can not only improve perioperative performance, relieve oxidative stress and lower inflammatory factor levels, but also effectively prevent complications.

Research Progress in the Regulation of Follicle Development by Melatonin / 中国医学科学院学报

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.

Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension / 生理学报

In this study, we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function. Three weeks after subcutaneous injection of MCT or normal saline, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter. Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation. The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation. Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels. The results showed that compared with control rats, RVSP and RVHI were significantly increased in the MCT-PAH rats, and both ACh or SNP-induced vasodilation were worsened. Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7) (1 × 10-9-1 × 10-4 mol/L) caused significant vaso-relaxation. Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation, but had no significant effect on SNP-induced endothelium-independent relaxation. In addition, Ang-(1-7) treatment significantly increased NO levels in HPAECs. The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells. The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor, thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.

Role of epigenetic regulation of biological clock genes in tumors / 中国药理学通报

The circadian clock is regulated at the molecular level by transcriptional-translational feedback loop of clock genes, which ensures that a variety of physiological processes have a-round 24 h circadian rhythms, including cell metabolism, cell proliferation, cell apoptosis and tumorigenesis, to maintain the homeostasis. Thus, the disturbance of circadian clock will disrupt homeostasis, causing various diseases, including neoplasm, metabolic syndrome, Parkinson's disease, COPD and cardiovascular diseases. Disturbance of circadian clock is closely related with tumorigenesis, and acts on various molecules and pathways leading to tumorigenesis, including oncogene and tumor suppressor gene, cell cycle, metabolic reprogramming, immune escape, endocrine disruption, alteration of gastrointestinal microbiome. This review focuses on changes in clock genes expression which disrupt cell cycle and may play a role in tumorigenesis, and epi-geneties, an important way to regulate gene expression, which can alter clock gene expression, thus playing an important role in the process of " the alternation of clock gene expression-disruption of cell cycle-tumorigenesis".

Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats / 中山大学学报(医学科学版)

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment / 药学学报

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

Research progress of amniotic membrane transplantation in the treatment of ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Amniotic membrane is the innermost membrane in human placenta. It supports epithelialization and has the characteristics of anti-fibrosis, anti-inflammation and anti-angiogenesis. It is gradually widely used in ophthalmic surgery and other surgical operations. In recently years, the amniotic membrane has been used more frequently in ophthalmic clinic and has achieved better curative effect. This article reviews the application of amniotic membrane transplantation in ocular diseases such as ocular burn, conjunctival disease, corneal disease, pterygium, glaucoma and macular hole. It is expected that amniotic membrane transplantation will bring new ideas for the treatment of ocular diseases.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Preliminary study on dicentric chromosome identification algorithm based on artificial intelligence technology / 中华放射医学与防护杂志

Objective:To explore artificial intelligence technology and propose an algorithm for automatic identification of dicentric chromosomes to realize fast and high-throughput biodosimetry. In order to solve the time-consuming and laborious problem of manual analysis of dicentric chromosomes.Methods:Combining artificial intelligence technology and image processing technology, based on MATLAB software, algorithms like image preprocessing, threshold segmentation algorithm, binarization processing, area identification algorithm, convolutional neural network algorithm and double centripetal recognition algorithm were applied. A fuzzy membership function was defined to describe the degree of each chromosome belonging to a dicentric chromosome, and the discrimination threshold was set to realize the automatic identification of dicentric chromosomes.Results:Through the test on 1 471 chromosome images, compared with manual recognition, the detection rate of dicentric chromosomes cells of this algorithm reached 70.7%.Conclusions:This algorithm method carries out a preliminary study on the automatic identification of dicentric chromosomes with good result.

Effect of Haikunshenxi capsule combined with losartan potassium tablets on renal function and inflammatory factors in patients with chronic kidney disease / 中国医师进修杂志

Objective:To investigate the curative effect of Haikunshenxi capsule combined with losartan potassium tablets on chronic kidney disease (CKD) and its effect on renal function and inflammatory factors.Methods:One hundred patients with chronic kidney disease in Shaoxing Central Hospital from January 2018 to December 2019 were selected and randomly divided into observation group (50 cases) and control group (50 cases). The control group was treated with losartan potassium tablets based on conventional therapy, and the observation group was treated with Haikunshenxi capsulebase on control group. The treatment course of the two groups was 12 weeks. The curative effect, renal function, inflammatory factors, 24h urinary protein (24 h Upro) and glomerular filtration rate (GFR) were compared between the two groups before and after treatment.Results:The total effective rate in the observation group was higher than that in the control group: 90.0%(45/50) vs. 72.0%(36/50), χ2 = 5.26, P<0.05. After treatment, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the two groups were decreased and the levels of Scr and BUN in the observation group were lower than those in the control group: (63.27 ± 2.89) μmol/L vs. (67.89 ± 2.35) μmol/L, (5.23 ± 0.19) mmol/L vs. (5.56 ± 0.16) mmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum C-reactive protein (CRP) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups were decreased and the levels of CRP, IL-6 and TNF-α in the observation group were lower than those in the control group: (2.97 ± 0.34) mg/L vs. (3.58 ± 0.42) mg/L, (3.64 ± 0.68) ng/L vs. (4.97 ± 0.96) ng/L, (14.32 ± 2.17) ng/L vs. (17.86 ± 2.06) ng/L, the differences were statistically significant ( P<0.05). After treatment, the level of 24 h Upro in two groups was decreased, while the level of GFR was increased, and the level of 24 h Upro in the observation group was lower than that in the control group: (0.87 ± 0.09) g vs. (1.15 ± 0.13) g , but the level of GFR in the observation group was higher than that in the control group: (101.73 ± 3.12) ml/(min·m 2) vs. (96.75 ± 2.35) ml/(min·m 2), the differences were statistically significant ( P<0.05). Conclusions:Haikunshenxi capsule combined with losartan potassium tablets has obvious curative effect on patients with chronic kidney disease, and can improve renal function and micro inflammation.

Muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting in the treatment of shoulder-hand syndrome after stroke / 针灸推拿医学（英文版）

Objective: To observe the effect of muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting in improving nail fold microcirculation in the patients with shoulder-hand syndrome (SHS) after stroke, and the effects on hemorrheology, calcitonin gene-related peptide (CGRP) and serum substance P (SP). Methods: A total of 72 patients were randomized into an observation group and a control group by the random number table method, with 36 cases in each group. The control group was treated with physical rehabilitation training, and the observation group was treated with additional muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting treatment. The treatment course lasted for 4 weeks. After treatment, the clinical efficacy of the two groups was compared. The changes in shoulder-hand syndrome scale (SHSS), simplified Fugl-Meyer assessment-upper extremity (FMA-UE), visual analog scale (VAS), activities of daily living (ADL), traditional Chinese medicine (TCM) syndrome score, nail fold microcirculation hemorheology indictors [whole blood viscosity (high-shear, low-shear), hematocrit, erythrocyte sedimentation rate (ESR)], CGRP and SP levels were observed. Results: The total effective rate in the observation group was 86.1％, higher than 63.9％ in the control group (P<0.05). The overall curative effect in the observation group was better than that in the control group (P<0.05). After treatment, the scores of pain sensation, edema, external turn and rotation of the arm in SHSS, and the total score were significantly decreased in both groups (all P<0.05), and each score in the observation group was lower than that in the control group (all P<0.05). After treatment, the scores of VAS and TCM syndrome in both groups decreased significantly (all P<0.05), and the scores of FMA-UE and ADL increased significantly (all P<0.05). The scores of VAS and TCM syndrome in the observation group were lower than those in the control group (both P<0.05), and the scores of FMA-UE and ADL were higher than those in the control group (both P<0.05). After treatment, the whole blood viscosity (high-shear and low-shear) and hematocrit in both groups decreased obviously (all P<0.05), and ESR increased obviously (both P<0.05), and the whole blood viscosity (high-shear and low-shear) and hematocrit in the observation group were lower than those in the control group (all P<0.05), and ESR was higher than that in the control group (P<0.05). After treatment, the peritubular state, loop shape, blood flow and total score of nail fold microcirculation in both groups decreased significantly (all P<0.05), and each score in the observation group was lower than that in the control group (all P<0.05). After treatment, SP in both groups decreased obviously (both P<0.05), CGRP increased obviously (both P<0.05), and SP in the observation group was lower than that in the control group (P<0.05), CGRP was higher than that in the control group (P<0.05). Conclusion: Compared with conventional physical rehabilitation training, muscle regions of meridians warm needling method plus pricking Jing-Well points for blood-letting treatment can significantly reduce the clinical symptoms of SHS, promote the recovery of physical functions, improve the nail fold microcirculation and hemorrheology indictors, and regulate the serum cytokine levels such as CGRP and SP.

Application value of contrast-enhanced ultrasound combined with thyroid imaging reporting and data system classification in the differential diagnosis of benign and malignant thyroid nodules / 中国基层医药

Objective:To investigate the application value of contrast-enhanced ultrasound (CEUS) combined with thyroid imaging reporting and data system (TI-RADS) classification in the differential diagnosis of benign and malignant thyroid nodules.Methods:The clinical data of 157 thyroid nodules from 122 participants who underwent conventional ultrasound and CEUS examination from January 2016 to January 2017 in the First Hospital of Shanxi Medical University, China were collected. The image features were analyzed for conventional ultrasound and TI-RADS classification. According to CEUS results, the thyroid nodules were classified by TI-RADS. Based on pathological results, the efficacy of CEUS combined with TI-RADS classification versus conventional ultrasound combined with TI-RADS classification in the differential diagnosis of benign and malignant thyroid nodules was investigated. Results:The area under the curve of CEUS combined with TI-RADS classification (AUC = 0.900) was greater than that of conventional ultrasound combined with TI-RADS classification (AUC = 0.808). The sensitivity, specificity, accuracy, positive and negative predictive values of conventional ultrasound combined with TI-RADS classification in the differential diagnosis of benign and malignant thyroid nodules were 81.6% (80/98), 67.8% (40/59), 76.4% (120/157), 80.8% (80/99), 68.9% (40/58), respectively. They were 98.0% (96/98), 78.0% (34/59), 90.4% (142/157), 88.1% (96/109), 95.8% (46/48), respectively for CEUS combined with TI-RADS classification. The sensitivity of CEUS combined with TI-RADS classification in the differential diagnosis of benign and malignant thyroid nodules was significantly higher than that of conventional ultrasound combined with TI-RADS classification ( χ2 = 12.50, P < 0.001). Conclusion:CEUS combined with TI-RADS classification is more effective in the differential diagnosis of benign and malignant thyroid nodules than conventional ultrasound combined with TI-RADS classification.

Relationship between free androgen index and insulin function in obese young men aged from 20 to 35 / 中华内分泌代谢杂志

Objective:To analyze the relationship between free androgen index and insulin function in obese young men aged from 20 to 35.Methods:A total of 82 young obese men in Obesity Clinic from February to October 2019 were enrolled in the study. The subjects were divided into 3 subgroups according to free androgen index level tertiles. The blood glucose and insulin levels were tested after oral glucose tolerance test. Homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β cell function (HOMA-β), insulin secretion index, and insulin sensitivity index (Matsuda index) were used to evaluate β cell function in oder to analyze the relationship between free androgen index and insulin function.Results:In young obese men, participants with higher free androgen index levels exhibited less waist circumference, lower body mass index, 1 h postprandial insulin, 2 h postprandial insulin, HOMA-IR level but with a higher total testosterone, sex hormone binding globulin, and Matsuda index level (all P<0.05). There was a negative correlation between the free androgen index and the HOMA-IR ( r=-0.386, P=0.016), and the correlation tended to a linear trend after adjustment for age, sex, body mass index, and waist circumference ( Ptrend=0.034). Free testosterone was positively correlated with Matsuda index ( r=0.280, P=0.004), but the correlation disappeared after adjustment ( Ptrend=0.623). The results of further regression analysis showed that the level of free testosterone index decreased by 14.1% ( OR=0.869, 95% CI0.767-0.984, P=0.028) for each increase of HOMA-IR after adjustment. Conclusion:The level of free testosterone index is a predictor of insulin resistance in obese young men, but the association between this parameter and insulin sensitivity may be caused by obesity.

Relationship between circadian rhythm sleep-wake disorders and the development of malignant tumor / 中国临床药理学与治疗学

The circadian rhythm regulates many physiological processes of the human body. The circadian rhythm sleep-wake disorder refers to a type of disease caused by the mismatch of sleep-wake cycle and circadian rhythm. It affects the human body's cognitive function and metabolic processes. The circadian rhythm sleep-wake disorder also promotes the growth of malignant tumors, directly and indirectly, by changing the expression of clock genes and inhibiting the secretion of melatonin. This article discusses circadian rhythm sleep-wake disorders; the subgroups it includes, the pathological state it causes, and the relationship between it and the development of malignant tumor. We hope to provide possible treatment measures for tumors affected by circadian sleep-wake disorders.

Model informed precision dosing: China expert consensus report / 中国临床药理学与治疗学

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Advances of the Regulation of microRNAs in Follicular Development / 中国医学科学院学报

In recent years,microRNAs(miRNAs)have been detected at different stages of follicular development and in different cells of follicles.Extracellular vesicle(EV)-derived miRNAs have also been detected in the follicular fluid of mature follicles.miRNAs participate in the regulation of normal follicular development,and the regulation disorder may lead to the occurrence of some ovarian diseases.In order to further systematically elucidate the regulatory mechanism of miRNAs on follicular development and find suitable EV-derived miRNAs that can predict oocyte development,we reviewed the functions of miRNAs in follicular development from the perspectives of granulosa cell development,oocyte development,and hormone synthesis.

Factors affecting the failure of non-invasive prenatal testing and the feasibility analysis of retesting / 中华医学遗传学杂志

OBJECTIVE@#To explore the cause for the failure of non-invasive prenatal testing (NIPT) and feasibility of repeated testing.@*METHODS@#Clinical data, test results and pregnancy outcomes of 40 311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed.@*RESULTS@#Among all the pregnant women, 1116 cases failed in the first test, 9 cases (0.81%) had fetal free DNA concentration lower than 4%, 663 cases (59.41%) were retested after the establishment of Z value gray area, and the remainder 444 cases (39.78%) needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%. After retesting, 1069 cases (95.78%) obtained effective NIPT results. The results showed that 53 cases were at high risk (6 cases for trisomy 21, 6 cases for trisomy 18, 13 cases for trisomy 13, 16 cases for sex chromosomal abnormality, 12 cases for chromosomal copy number variation). Forty-eight cases were selected for invasive prenatal diagnosis, and 2 cases of 47, XXY and 2 CNV were confirmed. A total of 47 cases (0.12%) did not obtain results because the concentration of fetal free DNA was lower than 4%. Only 16 cases (34%) chose invasive prenatal diagnosis.@*CONCLUSION@#Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis, and the feasibility of repeated detection is high. In the case of fetal free DNA concentration lower than 4%, the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age, but may delay the diagnosis for fetal aneuploidies. Therefore, personalized estimation should be made according to gestational age and clinical indications. It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.

Study on Quality Risk Management of Ethical Review of Dr ug Clin ical Trials / 中国药房

OBJECTIVE：To pro vide suggestions for imp roving the quality of ethical review of drug clinical trials in China and protecting the rights and interests of subjects. METHODS ：Guided by risk management theory ，the literature research method ， expert opinion method and analytic hierarchy process method were used to sort out the ethical review process of drug clinical trials ， extract and determine the risk factors that affect the quality of ethical review ，and determine the weight of each risk factor. Suggestions were put forward improving the ethical review of drug clinical trials in China. RESULTS & CONCLUSIONS ： Established ethical review risk index system of drug clinical trials included 31 influential factors of 5 aspects；the order of importance（weights）of 5 aspects affecting the quality of ethical review of drug clinical trials was as follows ：the construction of the medical ethics committee （0.263 5），the management of review meetings （0.251 4），follow-up review （0.194 5），the acceptance and processing of review applications （0.189 2），and the management of documents and files （0.101 4）. The influential factors with high weight included “withdrawal of people with conflict of interest in the discussion and voting process （0.078 7）” “timely review or conference discussion of scheme modification ，informed consent modification ，serious adverse events ，etc. （0.070 5）”“clarification and external exhibition of the work process and time of ethical review （0.059 8）”“unified and standardized review standards and approval standards （0.052 1）”，etc. The quality of ethical review can be improved by avoiding people with conflict of interest in the discussion and voting process ，timely reviewing or holding ethics meetings on scheme modification ， informed consent modification ，serious adverse events ，etc.，clarifying the working process and time of ethical review ，and establishing unified and standardized review standards and approval standards.

Effect of fractionated radiotherapy of transplanted hepatocellular carcinoma on the splenic immune cells in mice / 中华放射医学与防护杂志

Objective@#To investigate the effect of fractionated radiotherapy on the immune system of mice with subcutaneously transplanted hepatocellular carcinoma.@*Methods@#Logarithmic growth of mouse hepatocellular carcinoma cells Hepa 1-6 were inoculated subcutaneously on the right side of C57BL/6 J mice (1×107 cells /mice). The tumor-bearing mice were randomly divided into control group (Ctrl) and irradiation group (IR), 20 mice in each group. Additionally, 10 healthy mice were set as normal control group. Local fractionated X-ray irradiation of 8 Gy×3 fraction was given to the subcutaneous tumors, and the dose rate was 0.883 Gy/min. At 7 and 14 d after irradiation, the tumor organ index, spleen organ index, spleen pathological changes, and splenic T lymphocyte subsets, B lymphocyte subsets, and NK cells were detected.@*Results@#Compared with Ctrl, at 7 and 14 d after irradiation, the tumor organ index decreased (t=4.649, 26.34, P<0.05), and the percentage of NK cells increased significantly (t=3.952, 3.633, P<0.05). The percentages of CD3+ , CD4+ , CD3+ CD4+ lymphocytes and the ratio of CD4+ /CD8+ lymphocyte decreased at 7 d after irradiation (t=3.193, 3.656, 3.219, 2.641, P<0.05), and the percentage of CD3+ lymphocyte decreased at 14 d after irradiation (t=3.031, P<0.05). But after irradiation, there were no significant changes in spleen organ index, B lymphocyte, CD3+ CD4+ lymphocyte and CD8+ lymphocyte.@*Conclusions@#Local hepatoma radiotherapy causes imbalance of lymphocytes in distal spleen of mice and hence reduces immunity, which provides a novel mechanism of radiological immunity damage.