Analysis of factors for serious early complications after primary debulking surgery in elderly patients with advanced epithelial ovarian cancer / 中华老年医学杂志

Objective:To investigate the factors for serious complications within 30 days after surgery in elderly patients with advanced epithelial ovarian cancer(EOC)who undertook primary debulking surgery(PDS).Methods:The clinical data of International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC/Ⅳ EOC patients aged≥60 years who received PDS in gynecological department of National Cancer Center and National Center of Gerontology between January 2014 and December 2018 were retrospectively analyzed.Clavien-Dindo scoring system was applied to grade the complications within 30 days after surgery.The serious early postoperative complications were those of grade Ⅲ or above occurred within 30 days after surgery.Multivariate Logistic regression analysis was used to screen the independent risk factors of serious complications within 30 days after surgery.Results:A total of 133 patients were included in this study and serious complications rated 11.3%(15/133). The mean age of patients in severe complication group was significantly higher than that in the control group[(69.80±6.56) vs.(65.87±5.14), t=2.699, P=0.008]. The proportion of patients with preoperative ECOG score≥2 was significantly higher in the severe complication group than that in the control group[26.7%(4/15) vs.5.9%(7/118), χ2=4.985, P=0.026], and the proportion of preoperative hypoalbuminemia(<35 g/L)was significantly higher in the severe complication group[20.0%(3/15) vs.3.4%(4/118), χ2=4.897, P=0.027]. However, there was no significant difference in intraoperative bleeding, R0 resection rate as well as surgical complexity( χ2=1.964, 0.330, 4.637, all P>0.05)between the two groups.Multivariate Logistic regression analysis showed that the independent factors for serious early postoperative complications were age≥70 years( OR=4.345, P=0.028), ECOG score≥2( OR=25.619, P=0.008)and preoperative albumin <35 g/L( OR=6.733, P=0.040). Conclusions:In the elderly ovarian cancer patients, individualized perioperative management should be strengthened for the patients with factors associated with serious early postoperative complications, in order to reduce severe complications and improve the prognosis.

Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol / 中华劳动卫生职业病杂志

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 μmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3β (p-GSK3β) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 μmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3β were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

Characteristics of severe adenovirus pneumonia complicated with plastic bronchitis in children / 中国小儿急救医学

Objective:To summarize the clinical characteristics and investigate risk factors associated with the development of plastic bronchitis(PB)in pediatric patients who have severe pneumonia caused by adenovirus(HAdVs)infections.Methods:We retrospectively reviewed the clinical manifestations, laboratory results, radiological examinations, and treatment courses of 258 children who were diagnosed as HAdVs associated severe pneumonia between 1st January, 2015 and 31st October, 2019 at Shenzhen Children′s Hospital.According to the presence of PB, patients were divided into PB group( n=45)and non-PB group( n=213). Results:In PB group, the male to female ratio was 1.65∶1(including 28 boys and 17 girls)and the median age was 41.0(18.5, 65.5)months.Patients younger than 6 years of age accounted for 80.0%(36/45)and older patients accounted for 20.0%(9/45). The major clinical symptoms of patients in PB group were high fever(95.6%, 43/45), cough(100.0%, 45/45)and conjunctivitis(33.3%, 15/45). Physical examinations revealed that most patients had tachypnea(80.0%, 36/45)and crackles(80.0%, 36/45). Compared to patients in non-PB group, the duration of fever in PB group was significant longer( Z=-13.519, P<0.001). Compared to non-PB group, there was a significant decrease of the lymphocyte count[2.24(1.44, 3.84)×10 9/L vs.1.75(1.21, 3.03)×10 9/L] and a significantly increase of the procalcitonin level[0.46(0.19, 1.73)ng/mL vs.1.54(0.37, 2.96)ng/mL] in PB group( P<0.05). Chest radiological examinations revealed that patients in PB group had higher rates to develop pleural effusion(62.2% vs.42.3%) and atelectasis(57.8% vs.22.1%) of the lungs compared to non-PB group( P<0.05). The majority of patients improved after resolution of symptoms(97.8%, 44/45) in PB group.Only one patient(2.2%, 1/45) died due to discontinuation of treatment.Conjunctivitis( P<0.001, OR=108.514, 95% CI 17.476-673.791), tachypnea( P<0.001, OR=18.788, 95% CI 5.172-68.246), pleural effusion( P=0.007, OR=3.363, 95% CI 1.389-8.139) were independent risk factors associated with the development of PB in children with HAdVs associated severe pneumonia. Conclusion:Pre-school age children are at higher risk to develop HAdVs related severe pneumonia that complicated with PB.Fever and cough remain the main clinical symptoms.The presence of PB is associated with longer period of fever and higher risks to have pleural effusion and atelectasis.Conjunctivitis, tachypnea orpleural effusion are higher risk to develop PB in those with HAdVs associated severe pneumonia.

Effects of oxidative stress, PSMB5, TFEB, and lysosomes on sodium arsenite-induced liver injury in rats / 环境与职业医学

Background Liver damage presented in endemic arsenic poisoning is usually serious. Studies have shown that oxidative stress, proteasome beta 5 subunit (PSMB5), regulatory transcription factor EB (TFEB), and lysosomes are associated with liver injury, but their specific links to arsenic-induced liver injury remain unclear. Objective Using a sodium arsenite (NaAsO2)-induced rat liver injury model established earlier by the research group, the expressions of PSMB5, TFEB, and lysosomal associated membrane protein 1 (LAMP1) in liver tissues were detected. Methods Twenty-four SPF Wistar rats were randomly divided into control group, and low, medium, and high dose groups, with 6 rats in each group, half male and half female. The exposure concentrations were 0, 25, 50, and 100 mg·L−1 NaAsO2 solutions for 24 weeks. At the end of the experiment, liver was dissected after rats were anesthetized. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bile acid (TBA), and catalase (CAT) in liver tissues were detected by chemical colorimetry, and the levels of lipid peroxide (LPO), 4-hydroxynonenal (4-HNE), LAMP1, and cathepsin D (CTSD) in liver tissues were detected by enzyme-linked immunosorbent assay (ELISA); the transcriptional expression levels of PSMB5 and TFEB in liver tissues were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the protein expressions of PSMB5, TFEB, and phosphorylated TFEB (p-TFEB) in liver tissues were detected by immunohistochemistry. Results The results of chemical colorimetry and ELISA showed that compared with the control group, the liver homogenate levels of ALP, TBA, and LAMP1 of each arsenic-exposed group, the ALT and LPO in the medium and high concentration groups, the 4-HNE and CTSD in the high concentration group were increased, while the CAT activity of each arsenic-exposed group was decreased (P<0.05). The results of real-time fluorescence quantitative PCR showed that the transcription levels of PSMB5 and TFEB in the liver tissues of each arsenic-exposed group were decreased compared with those of the control group (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression of PSMB5 of each arsenic-exposed group were decreased, the expression of TFEB in the medium and high concentration groups was decreased, while the expression of p-TFEB of each arsenic-exposed group was increased (P<0.05). The expression of TFEB protein gradually decreased in the nucleus, while the expression of p-TFEB protein gradually increased in the cytoplasm, but no expression of p-TFEB was found in the nucleus. The results of Pearson correlation analysis showed that PSMB5 in liver tissues was positively correlated with CAT (r=0.818, P＜0.05), and negatively correlated with 4-HNE and p-TFEB (r=−0.582, r=−0.899; P＜0.05); TFEB was negatively correlated with CTSD and LAMP1 (r=−0.457, r=−0.564; P＜0.05); CTSD was positively correlated with ALT and ALP (r=0.529, r=0.485; P＜0.05). Conclusion Long-term exposure to NaAsO2 can induce oxidative stress, inhibit the expression of PSMB5 and TFEB, promote the accumulation of p-TFEB in the cytoplasm, decrease the nuclear entry of active TFEB, damage the lysosome, and cause liver damage.

Molecular biological characteristics of the 2019 novel Coronavirus in Shijiazhuang / 中华检验医学杂志

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses

Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact

Analysis and Enlightenment of Foreign Open Breast Image Datasets / 中国医学科学院学报

With the upsurge of medical artificial intelligence,the use of computer vision technology to study medical images,which can effectively help doctors to identify and screen diseases,has become a focus of researchers.This paper summarizes the basic situation,specific information,related research,and data sharing and utilizing ways of foreign breast image datasets.This review provides inspirations for the opening of Chinese medical and health data.

Clinical feature analysis of 541 children with adenovirus pneumonia / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics of adenovirus (HAdVs) pneumonia in children.Methods:The clinical manifestations, laboratory results, imaging features and treatment courses of 541 children with HAdVs pneumonia treated in Shenzhen Children′s Hospital from January 2017 to August 2019 were retrospectively studied.Results:The number of children diagnosed with HAdVs pneumonia increased year by year.A total of 541 patients were included in this study (214 females and 327 males, median age 31 months). The majority of patients (89.3%, 483/541 cases) were less than 6 years of age.Cough (98.3%, 532/541 cases) was the most common symptom, followed by fever (93.7%, 507/541 cases), tachypnea (36.6%, 198/541 cases) and wheeting (32.5%, 176/541 cases). Thirteen point three percent patients (72/541 cases) had existing primary diseases.Severe HAdVs pneumonia was observed in 33.8% of patients (183/541 cases), the most common intrapulmonary complication were pleural effusion(18.6%, 101/541 cases) and respiratory failure (7.0%, 38/541 cases). In co-infection cases, 46.9% of the patients (254/541 cases) suffered from co-infection with mycoplasma pneumoniae, 21.6% of the patients (117/541 cases) suffered from bacterial co-infection.Ninety-eight point five percent of the patients (533/541 cases) were cured, and 1.5% of the patients (8/541 cases) died or discharged voluntarily.Convulsions [ P=0.026, OR=7.312 (95% CI: 1.267-42.191)] and bacterial co-infections [ P=0.030, OR=2.724 (95% CI: 1.101-6.741)] were independently correlated with the occurrence of severe HAdVs pneumonia. Conclusions:Pre-school aged children are at higher risks of developing HAdVs pneumonia.The majority of patients presents with fever and cough as primary manifestations.Tachypnea and wheezing are also common clinical features of HAdVs pneumonia patients.Approximately a third of children with HAdVs pneumonia may develop into severe pneumonia.The presentation of convulsion and the exis-tence of bacterial co-infections may help to predict the development of severe HAdVs pneumonia in pediatric patients.

Role of oxidative stress-induced AMPK/ULK1 pathway activation and lysosomal dysfunction in arsenic-induced liver injury in rats / 环境与职业医学

Background A prominent feature of endemic arsenic poisoning is severe liver damage. Studies have found that liver injury is closely related to oxidative stress, lysosomes, and autophagy. Objective Through establishing a liver injury model of rats by sodium arsenite (NaAsO2)administration in drinking water, this experiment is designed to explore the roles of oxidative stress, lysosomes, and AMP activated protein kinase (AMPK)/Unc-51 like kinase 1 (ULK1) pathway in this model. Methods Twenty-four Wistar rats were randomly divided into four groups with six rats in each group (half male and half female), including control group and 25, 50, 100 mg·L−1 NaAsO2 groups. A rat liver injury model was established by drinking water containing NaAsO2 freely for 24 weeks. Then liver of rats was dissected after sacrificed, and the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA), catalase (CAT), lipid peroxidation (LPO), and total antioxidant capacity (T-AOC) in liver tissues were detected by assay kits. The levels of lysosomal-associated membrane protein 2 (LAMP2), cathepsin B (CTSB), and acid phosphatase (ACP2) were determined by enzyme linked immunosorbent assay. The mRNA transcriptional expressions of AMPK, ULK1, microtubule-associated protein light chain 3 (LC3), and sequestosome 1 (p62) were detected by real-time fluorescence quantitative PCR (RT-qPCR). The protein expressions of p-AMPK, p-ULK1, LC3, and p62 were detected by immunohistochemistry. Results Following the NaAsO2 administration, significant differences were found in the levels of ALT, ALP, and TBA among the designed groups (F=12.09, 72.11, and 23.58, P<0.05). Compared with the control group, the levels of ALT in the 50mg·L−1 and 100 mg·L−1 NaAsO2 groups were increased (P<0.05); the levels of ALP and TBA in the 25, 50, and 100 mg·L−1 NaAsO2 groups were increased (P<0.05); the level of LPO in the 100 mg·L−1 group was increased (P<0.05); the levels of CAT and T-AOC in the 25, 50, and 100 mg·L−1 NaAsO2 groups were decreased (P<0.05). According to the results of enzyme linked immunosorbent assay, the levels of ACP2 in the 25, 50, and 100 mg·L−1 NaAsO2 groups, the level of CTSB in the 100 mg·L−1 NaAsO2 group, and the levels of LAMP2 in the 50 and 100 mg·L−1 NaAsO2 groups were decreased compared with the control group (P<0.05). Based on the results of RT-qPCR and immunohistochemistry, the mRNA transcriptional and protein expressions of AMPK, ULK1, and LC3 in some arsenic groups were elevated to varying degrees compared with the control group, and the increment in the 100 mg·L−1 NaAsO2 group was significant for all the indicators (P<0.05); the mRNA transcriptional expressions of p62 in the three arsenic groups and the protein expressions of p62 in the 50 and 100mg·L−1 NaAsO2 groups also increased compared with the control group (P<0.05). Besides, the results of Pearson correlation analysis showed that there was a positive correlation of T-AOC with LAMP2, CTSB, and ACP2 (r=0.651, 0.673, 0.626; P<0.05), a negative correlation of LPO with CTSB and ACP2 (r=−0468, −0.482; P<0.05), a negative correlation of p62 with LAMP2, CTSB, and ACP2 (r=−0.57, −0.626, −0.591; P<0.05), and a positive correlation of p62 with ALT, ALP, and TBA (r=0.709, 0.897, and 0.857, P<0.05). Conclusion Long-term arsenic exposure may induce oxidative stress, damage lysosomes, and activate the AMPK/ULK1 pathway, which can lead to the blockage of autophagy process, and eventually result in liver damage.

Effects of SSRI Antidepressants on Attentional Bias toward Emotional Scenes in First-Episode Depressive Patients: Evidence from an Eye-Tracking Study

Objective@#Attentional biases toward emotional scenes may represent vulnerability and maintenance factors in depression. Antidepressant therapy may improve cognitive function and reduce depression, and is considered as the mechanism of action of antidepressants. Therefore, we conducted an eye-tracking test to examine whether selective serotonin re-uptake inhibitor (SSRI) antidepressants can reduce negative attentional biases and elicit clinical responses in depression. @*Methods@#Twenty first-episode depressive patients freely viewed three types of pictures that depicted different emotional scenes (i.e., positive-control, neutral-control, and negative-control) for 4,000 ms while their eye movements were monitored. The attentional bias to different emotional scenes was assessed before and after eight weeks of SSRI treatment using the eye-tracking method. The control group included a group of healthy individuals. @*Results@#The results revealed that first-episode depressive patients oriented their gaze more frequently to negative images and less to happy images, compared to controls. Importantly, the attentional bias in depressive patients was regulated after eight weeks of SSRI treatment. Patients showed an increased tendency to fixate on positive images and a decreased tendency to focus on negative images. @*Conclusion@#This suggests that SSRI antidepressants decrease vulnerability to negative images, while having an effect on attention in respect to positive images.

LC-MS/MS analysis of pharmacokinetics of 3, 29-dibenzoyl karounitriol in rats following administration of Trichosanthes sustained-release pellets / 南方医科大学学报

OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.

Effect of new simple breathing apparatus on oxygen therapy in patients with severe and critical coronavirus disease 2019 / 中华危重病急救医学

Objective:To make a new simple respirator and observe the oxygen therapy effect of the respirator on patients with severe and critical coronavirus disease 2019 (COVID-19).Methods:Based on the infectivity and hospital requirements of COVID-19, a new simple respirator was designed by the medical staff of the Department of Anesthesiology of the Second Affiliated Hospital of Nanchang University, which was applied on the 22 patients with severe and critical COVID-19 who needed oxygen therapy admitted to the Cancer Center of Tongji Medical College of Huazhong University of Science and Technology from February 15th to March 15th in 2020. The new simple respirator contained two National Utility Model Patents (a respirator: ZL 2015 2 0410623.6, a fluid switch and oxygen suction device: ZL 2017 2 0873509.6), which was mainly composed of anesthesia mask and filter, L-shaped connecting tube, soft breathing bladder, connecting tube and elastic fixing belt. When in use, the anesthesia mask was fixed to the patient's mouth and nose with elastic straps, the connecting tube was inserted into the oxygen meter interface, the oxygen flow was adjusted to 6-10 L/min, and the L-shaped connecting tube was opened immediately after the soft breathing bag was full. The carbon dioxide and excess oxygen in the body was discharged from exhaust port. The oxygen flow was lowered to 2-3 L/min, the patient's respiratory rate (RR) was observed through the soft breathing bag fluctuations, and the oxygen flow was adjusted at any time. The changes of pulse oxygen saturation (SpO 2), RR and heart rate (HR) before and after application of new simple respirator were observed, and the blood gas test results of part of the patients were collected. Results:Twenty-two patients with severe and critical COVID-19 had significantly higher SpO 2 at 10 minutes after application of the new simple ventilator than before application (0.994±0.007 vs. 0.952±0.017, P < 0.01), and RR was significantly lower than that before application (times/min: 27.59±3.63 vs. 29.64±3.81, P < 0.01); after 1 day of application, each index was further improved. All 13 patients who received blood gas analysis indicated no carbon dioxide accumulation. Conclusions:The new simple respirator can significantly improve the oxygen therapy effect of patients with severe and critical COVID-19. At the same time, 2019 novel coronavirus (2019-nCoV) can be filtered through the filter to reduce the formation of aerosol and protect the medical staff and patients.

Role of reactive oxygen species-mitochondrial pathway in sodium arsenite-induced apoptosis of L-02 cells / 中华地方病学杂志

Objective:To explore the mechanism of apoptosis induced by sodium arsenite (NaAsO 2) in human hepatic cells (L-02) through reactive oxygen species (ROS) accumulation and mitochondrial dysfunction, and provide experimental evidence for the mechanism of arsenic poisoning. Methods:L-02 cells were divided into control group, NaAsO 2 group (10 μmol/L NaAsO 2), N-acetylcysteine (NAC) group (5 mmol/L NAC), and NaAsO 2 + NAC group (10 μmol/L NaAsO 2, 5 mmol/L NAC), and were cultured in vitro for 24 h. The intracellular ROS level, mitochondrial membrane potential depolarization ratio and cell apoptosis rate were measured by dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence probe, JC-1 staining and Annexin V-FITC/PI double staining, respectively; the mRNA and the protein of Caspase 3, cytochrome C (Cyt-C) and cytochrome C oxidaseⅣ (COXⅣ) were detected by real time fluorescence quantitative PCR (qRT-PCR) and Western blotting, respectively. Results:There were statistically significant differences in intracellular ROS levels (3 857 392.33 ± 44 928.39, 4 515 288.00 ± 32 660.64, 3 670 150.67 ± 101 987.69, 4 035 235.67 ± 99 995.30), mitochondrial membrane potential depolarization ratios (2.16 ± 0.54, 7.95 ± 0.52, 2.70 ± 0.29, 1.01 ± 0.23) and total apoptosis rates (1.45 ± 0.03, 4.27 ± 0.17, 1.87 ± 0.12, 2.52 ± 0.35) between groups ( F = 62.62, 159.81, 112.70, P < 0.05). There were statistically significant differences in Caspase 3, Cyt-C, COXⅣ mRNA expression levels ( F = 9.20, 7.33, 14.87, P < 0.05) and in cleaved-Caspase 3, Cyt-C, COXⅣ protein expression levels( F = 31.42, 8.01, 83.30, P < 0.05) between groups. Compared with the control group, the intracellular ROS level, mitochondrial membrane potential depolarization ratio and total apoptosis rate were significantly increased ( P < 0.05); Caspase3, Cyt-C mRNA and protein expression levels were significantly increased ( P < 0.05), and COXⅣ mRNA and cleaved-Caspase 3, Cyt-C protein expression levels were significantly decreased ( P < 0.05) in NaAsO 2 group. Compared with the NaAsO 2 group, the intracellular ROS level, mitochondrial membrane potential depolarization ratio and total apoptosis rate of NaAsO 2 + NAC group were significantly decreased ( P < 0.05); the Caspase3, Cyt-C mRNA and cleaved-Caspase 3, Cyt-C protein expression levels were significantly decreased ( P < 0.05), the COX Ⅳ mRNA and protein expression levels were significantly increased ( P < 0.05). Conclusions:NaAsO 2 stimulates L-02 cells to produce excessive ROS, which induces mitochondrial depolarization and further triggers mitochondrial damage, resulting in increased release of Cyt-C and activation of the mitochondrial apoptosis pathway that Caspase 3 protein induces apoptosis in L-02 cells, which may be one of the main mechanisms of arsenic-induced liver injury.

LC-MS/MS analysis of pharmacokinetics of 3, 29-dibenzoyl karounitriol in rats following administration of Trichosanthes sustained-release pellets / 浙江大学学报·医学版

OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.

Mechanisms for establishment of the placental defensive barrier / 生理学报

Placenta serves as a temporary fetal organ, which mediates maternal-fetal crosstalk and intrauterine fetal growth. Placental defensive barrier is a fundamental physiological function, which balances maternal immune tolerance to the fetus and resistance to pathogens. This review summarizes the latest research progress on the mechanisms of placental barrier formation from the view of placental development. Recent discoveries have shed light on the cellular and molecular properties of placental defensive mechanisms in syncytiotrophoblast, including autophagy, exosome mediated anti-pathogenic pathways, cell-cell junctions and cytoskeleton networks. We also present an overview of placental barrier dysfunction and its implications in intrauterine TORCH infections.

Investigation of relationship of serum and carcinoma levels of plasminogen activator inhibitor-1 with the invasion and metastasis of endometrial carcinoma / 中华老年医学杂志

Objective To investigate the relationship of serum and carcinoma levels of plasminogen activator inhibitor-1 (PAI-1)with clinical characteristics in patients with endometrial carcinoma.Methods Serum level of PAI-1 was determined by using enzyme-linked immunosorbent assay(ELISA) in patients with endometrial carcinoma (n =40),uterine prolapsed with normal endometrial tissues(n=40).The protein expression of PAI-1 in endometrial tissue was detected by using immunohistochemistry in patients with endometrial carcinoma and uterine prolapse patients.Results Serum level of PAI-1 was higher in patients with endometrial carcinoma than in uterine prolapse patients with normal endometrial tissues(19.43±7.12 μg/L vs.6.58±2.33 μg/L,P＜0.05).The rate of positive expression of PAI-1 was higher in endometrial carcinoma tissue than in uterine prolapse tissue[62.5 ％ (25/40) vs.7.5 ％ (3/40),P ＜ 0.01].Compared with early-stage endometrial carcinoma,advanced endometrial carcinoma had an increased rate of positive expression of PAI-1 (P ＜0.01).Compared with endometrioid adenocarcinoma,other pathological types of endometrial carcinoma had an increased rate of positive expression of PAI-1 (P ＜ 0.05).Poorly differentiated endometrial carcinoma versus highly differentiated endometrial carcinoma had an increased positive rate of PAI-1 (P ＜0.05).The rate of positive expression of PAI-1 was higher in endometrial carcinoma with myometrial invasion than without myometrial invasion(25/31 vs.0/9,P＜0.01).Conclusions The expression level of PAI-1 may be related to the invasion and metastasis of endometrial carcinoma.

Improvement Effects of Water Extract of Glycyrrhiza uralensis on Acute Hepatic Injury Caused by Triptolide and Its Effects on the Levels of IL- 10 and TNF-α in Rats / 中国药房

OBJECTIVE： To observe the improvement effects of water extract of Glycyrrhiza uralensis on acute hepatic injury caused by triptolide and its effects on the levels of IL-10 and TNF-α in rats. METHODS： A total of 60 healthy male SD rats were randomized into blank control group， model group， positive control group （magnesium isoglycyrrhizinate） and G. uralensis water extract low-dose， middle-dose and high-dose groups. Blank control group and model group were given isochoric normal saline intragastrically； positive control group was given Magnesium isoglycyrrhizinate liquid intragastrically （13.5 mg/kg）； G. uralensis water extract low-dose， middle-dose and high-dose groups were given G. uralensis water extract intragastrically 1 mL （120， 240， 480 mg/kg， by the amount of extract）， qd， for consecutive 7 d. At 8th day of administration， model group， positive control group and G. uralensis water extract groups were given Triptolide liquid intragastrically （0.6 mg/kg） to establish acute liver injury model. HE staining was used to detect the pathological changes of liver tissue in rats. The activities of ALT and AST in serum were determined by enzyme coupling reaction. The protein expression of IL-10 and TNF-α in liver tissue were analyzed by Western blotting. RESULTS： Compared with blank control group， obvious pathological changes of liver tissue in rats were observed in model group； serum activities of ALT and AST， the protein expression level of TNF-α in liver tissue were increased significantly， while the protein expression level of IL-10 was decreased significantly （P＜0.01）. Compared with model group， pathological changes of liver tissue were relieved significantly. Except for the activity of AST in serum of rats in G. uralensis water extract low-dose group， the activities of ALT and AST in serum， the protein expression level of TNF-α in liver tissue were decreased significantly in G. uralensis groups， while the protein expression level of IL-10 in liver tissue was increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： G. uralensis water extract can relieve triptolide-induced acute liver injury in rats， the mechanism of which may be associated with expression down-regulation of pro-inflammatory factor TNF-α and expression up-regulation of anti-inflammatory factor IL-10.

Quantitative Expression of RNA from Frozen Organs and Formaldehyde-fixed and Paraffin-embedded Tissues / 法医学杂志

Objective Quantitative analysis and comparison of the expression of ribonucleic acid （RNA） from frozen organs and formaldehyde-fixed and paraffin-embedded （FFPE） tissues. Methods Frozen specimens of human brain, myocardium and liver tissues as well as FFPE samples at different postmortem intervals were collected and mass concentration of RNA was extracted and detected. Reverse transcription-quantitative polymerase chain reaction （RT-qPCR） technology was used to analyze the amplification efficiency and relative expression of each RNA marker. Results The mass concentration and integrity of RNA extracted from FFPE samples were relatively low compared with frozen specimens. The amplification efficiency of RNA markers was related with RNA species and the length of amplification products. Among them, glyceraldehyde-3-phosphate dehydrogenase （GAPDH） and β-actin （ACTB） with relatively long amplification products failed to achieve optimal amplification efficiency, whereas 5S ribosomal RNA （5S rRNA） achieved ideal amplification efficiency and showed quite stable expression across various tissues, therefore it was chosen as internal reference marker. The expression quantity of GAPDH and ACTB in frozen specimens with longer postmortem intervals and in FFPE samples with relatively long amplification products was decreased. The expressions of tissue-specific microRNAs （miRNAs）, GAPDH and ACTB with relatively short amplification products had consistency in the same tissues and FFPE samples. Conclusion Through standardizing the RT-qPCR experiment, selecting the appropriate RNA marker and designing primers of appropriate product length, RNA expression levels of FFPE samples can be accurately quantified.

A retrospective analysis of infection and antimicrobial susceptibility of genital mycoplasma in Changsha from 2010 to 2017 / 中华检验医学杂志

Objective@#To study the prevalence and antimicrobial susceptibility of Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) in Changsha, and provide laboratory evidence for clinical drug use.@*Methods@#A retrospective study was conducted to analyze 53 006 specimens of suspected genital mycoplasma infection in Xiangya Second Hospital of Changsha District and Hunan Wangwang Hospital from 2010 to 2017, and to analyze the infection rate and drug resistance rate of Uu and Mh.@*Results@#From 2010 to 2017, a total of 53 006 specimens were detected, where there were 16 830 cases of Uu infection, the infection rate was 31.75%; 2 471 cases of Mh infection, the infection rate was 4.66%; and 1 071 cases of Uu and Mh mixed infection, the infection rate was 2.02%. Male Uu infection rate was 19.48%(5 989/30 749), which was lower than the female infection rate 48.71%(10 841/22 257) (χ2=5 091, P<0.001); male Mh infection rate was 3.16%(973/30 749), lower than female infection rate 6.73%(1 498/22 257) (χ2=369,P<0.001). The population of genital mycoplasma infection is concentrated between 20 and 40 years old, accounting for 71.76% (12 077/16 830). The drug resistance rates of Uu and Mh to doxycycline and minocycline were less than 2%, while the drug resistance rate to quinolones was higher; The resistance rate of Uu to macrolide antibiotics such as erythromycin, josamycin and clarithromycin were less than 2%, while the resistance rate to azithromycin, erythromycin and roxithromycin were higher, 29.74%(5 006/16 830) and 53.74%(9 045/16 830), respectively, and the resistance rate of Mh to macrolide antibiotics (except josamycin) was higher than 90%.Between 2010 and 2017, a gradually increasing resistance of ureaplasmas to azithromycin, from 3.81% (46/1 206) in 2010 to 53.15% (1 503/2 828) in 2017, and decreasing resistance to gatifloxacin and thiamphenicol were observed, from 76.78% (926/1 206) and 60.28% (727/1 206) in 2010 decreased to 34.23% (968/2 828) and 37.87% (1 071/2 828) in 2017, respectively. The resistance rate of Mh to gatifloxacin and thiamphenicol were decreased, from 68.93% (122/177) and 41.81% (74/177) in 2010 to 53.54% (159/297) and 21.21% (63/297) in 2017, respectively.@*Conclusions@#Doxycycline, minocyclinum and josamycin are good treatment options for genital mycoplasma in Changsha. The resistance rate of Uu to azithromycin is increasing, suggesting that the abuse of azithromycin is present in Changsha, and indicating that better management of antibiotics is necessary.

Value of Duration of Myocardial Early Systolic Lengthening Assessed by Echocardiogram on Defining the Degree of Coronary Artery Stenosis / 中国循环杂志

Objectives: To evaluate the degree of coronary artery stenosis with duration of myocardial early systolic lengthening derived from 2D speckle tracking imaging (2D-STD in patients with coronary artery disease (CAD). Methods: 185 patients with suspected CAD underwent 2D-STI before coronary CT angiography (CCTA) were included in this study. Duration of myocardial early systolic lengthening, LS, RS, and CS were measured by 2D-STI. According to the results of CCTA, the myocardial segment were divided into normal group (without coronary artery stenosis), mild stenosis group(coronary artery stenosis<50%), moderate stenosis group (50%>coronary artery stenosis < 70%) and severe stenosis group (70%>coronary artery stenosis <100%). Results: Duration of myocardial early systolic lengthening, LS, RS and CS were similar between mild stenosis group and normal group (P>0.05). Duration of myocardial early systolic lengthening was increased, and LS was decreased in moderate stenosis group than in normal group (P<0.05). Duration of myocardial early systolic lengthening was increased, LS, RS and CS were significantly decreased in severe stenosis group than in normal group (P<0.01). The cutoff value of early systolic lengthening for diagnose severe stenosis was 60.0 ms (area under ROC curve [AUCl=0.91, P<0.01), with the sensitivity 85.5% and specificity 74.1%, respectively. Conclusions: Duration of myocardial early systolic lengthening is prolonged in patients with significant CAD (moderate and severe stenosis), and might be used a useful parameter to identify patients with significant CAD (moderate and severe stenosis).