Maresin1 inhibits the NF-κB/caspase-3/GSDME signaling pathway to alleviate hepatic ischemia-reperfusion injury / 中华肝脏病杂志

Objective: To investigate the role of Maresin1 (MaR1) in hepatic ischemia-reperfusion injury (HIRI). Methods: The HIRI model was established and randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (IR group), and a MaR1 ischemia-reperfusion group (MaR1+IR group). MaR1 80ng was intravenously injected into each mouse's tail veins 0.5h before anesthesia. The left and middle hepatic lobe arteries and portal veins were opened and clamped. The blood supply was restored after 1h of ischemia. After 6h of reperfusion, the mice were sacrificed to collect blood and liver tissue samples. The Sham's group abdominal wall was only opened and closed. RAW267.4 macrophages were administered with MaR1 50ng/ml 0.5h before hypoxia, followed by hypoxia for 8h and reoxygenation for 2h, and were divided into the control group, the hypoxia-reoxygenation group (HR group), the MaR1 hypoxia-reoxygenation group (MaR1 + HR group), the Z-DEVD-FMK hypoxia-reoxygenation group (HR+Z group), the MaR1 + Z-DEVD-FMK hypoxia-reoxygenation group (MaR1 + HR + Z group), and the Con group without any treatment. Cells and the supernatant above them were collected. One-way analysis of variance was used for inter-group comparisons, and the LSD-t test was used for pairwise comparisons. Results: Compared with the Sham group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, and IL-18 in the IR group were significantly higher (P < 0.05), with remarkable pathological changes, while the level in the MaR1 + IR group was lower than before (P < 0.05), and the pathological changes were alleviated. Compared with the Con group, the HR group had higher levels of IL-1β and IL-18 (P < 0.05), while the MaR1 + HR group had lower levels of IL-1β and IL-18 (P < 0.05). Western blot showed that the expressions of caspase-3, GSDME, and GSDME-N were significantly higher in the HR group and IR group than in the other groups; however, the expression was lower following MaR1 pretreatment. The Z-DEVD-FMK exploration mechanism was inhibited by the expression of caspase-3 in HIRI when using MaR1. Compared with the HR group, the IL-1β and IL-18 levels and the expressions of caspase-3, GSDME, and GSDME-N in the HR + Z group were decreased (P < 0.05), while the expression of nuclear factor κB was increased, but following MaR1 pretreatment, nuclear factor κB was decreased. There was no significant difference in the results between the MaR1 + H/R group and the MaR1 + H/R + Z group (P > 0.05). Conclusion: MaR1 alleviates HIRI by inhibiting NF-κB activation and caspase-3/GSDME-mediated inflammatory responses.

Exploration of making removable partial denture by digital technology / 中华口腔医学杂志

To explore the digital manufacturing process of distal extension removable partial denture. From November 2021 to December 2022, 12 patients (7 males and 5 females) with free-ending situation were selected from the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University. Three-dimensional model of the relationship between alveolar ridge and jaw position was obtained by intraoral scanning technique. After routine design, manufacturing and try-in of metal framework for removable partial denture, the metal framework was located in the mouth and scanned again to obtain the composite model of dentition, alveolar ridge and metal framework. The free-end modified model is obtained by merging the digital model of free-end alveolar ridge with the virtual model with the metal framework. The three-dimensional model of artificial dentition, and base plate was designed on the free-end modified model, and the resin model were made by digital milling technology. The removable partial denture was made by accurately positioning the artificial dentition and base plate, bonding metal framework with injection resin, grinding and polishing the artificial dentition and resin base. Compared with the design data after clinical trial, the results showed that there was an error of 0.4-1.0 mm and an error of 0.03-0.10 mm in the connection between the resin base of artificial dentition and the connecting rod of the in-place bolt and the connection between artificial dentition and resin base. After denturen delivery, only 2 patients needed grinding adjustment in follow-up visit due to tenderness, and the rest patients did not find any discomfort. The digital fabrication process of removable partial denture used in this study can basically solve the problems of digital fabrication of free-end modified model and assembly of artificial dentition with resin base and metal framework.

Improving the understanding of PI-RADS in practice: characters of PI-RADS 4 and 5 lesions with negative biopsy / 亚洲男科学杂志(英文版)

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.

MTBSTFA derivatization-LC-MS/MS approach for the quantitative analysis of endogenous nucleotides in human colorectal carcinoma cells / 药物分析学报

Endogenous ribonucleotides(RNs)and deoxyribonucleotides(dRNs)are important metabolites related to the pathogenesis of many diseases.In light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with N-(t-butyldimethylsilyl)-N-methyltri-fluoroacetamide(MTBSTFA)was developed to determine RNs and dRNs in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85％methanol followed by a simple derivatization reaction within 5 min at room temper-ature contributed to shortened analysis time.The derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical Cig column and eluted by ammonium acetate and acetonitrile in 9 min.Under these optimal conditions,good linearity was achieved in the tested calibration ranges.The lower limit of quantitation(LLOQ)was determined to be 0.1-0.4 μM for the tested RNs and 0.001-0.1 μM for dRNs.In addition,the precision(CV)was＜15％and the RSD of stability was lower than 10.4％.Furthermore,this method was applied to quantify the endogenous nucleotides in human colorectal carcinoma cell lines HCT116 exposed to 10-hydroxycamptothecin.In conclusion,our method has proven to be simple,rapid,sensitive,and reliable.It may be used for specific expanded studies on intracellular pharmacology in vitro.

Relationship between interpregnancy interval and neurodevelopment among 6-month-old infants / 预防医学

Objective@#To examine the relationship between interpregnancy interval (IPI) and neurodevelopment among 6-month-old infants, so as to provide insights into the prevention of neurodevelopmental abnormalities among infants.@*Methods@#Puerparas with full-term delivery at Anhui Province Maternity and Child Health Hospital from April 2017 to July 2018 and their babies were recruited. The demographic features, behaviors during pregnancy, IPI and birth outcomes were collected through questionnaires and medical records. The neurodevelopment was evaluated using the Ages and Stages Questionnaire (third edition) among infants at 6 months of age. The association between IPI and neurodevelopment was examined using multivariable logistic regression analysis.@*Results @#Totally 485 maternal-newborn pairs were investigated, and the puerparas had a mean age of ( 29.43±4.40 ) years. There were 330 puerparas ( 68.04% ) with normal pre-pregnancy body mass index, 325 puerparas ( 67.01% ) with eutocia, 233 puerparas (48.04%) with the first delivery, 44 puerparas ( 9.07% ) with IPI of less than one year and 208 puerparas ( 42.89% ) with IPI of one year and greater. There were 246 male babies ( 50.72% ) and 437 babies ( 90.10% ) with normal birth weight. A total of 148 newborns were diagnosed with neurodevelopmental abnormalities, with a detection rate of 30.52%. Of all newborns with neurodevelopmental abnormalities, there were 45 babies with communication abnormalities ( 9.28% ), 87 babies with gross motor abnormalities ( 17.94% ), 73 babies with fine motor abnormalities ( 15.05% ), 68 babies with abnormalities of solving problems ( 14.02% ) and 60 babies with personal-social abnormalities ( 12.37% ). Multivariable logistic regression analysis showed a reduced risk of infant's communication abnormalities ( OR=0.273, 95%CI: 0.090-0.833 ), gross motor abnormalities ( OR=0.340, 95%CI: 0.150-0.770 ), fine motor abnormalities ( OR=0.266, 95%CI: 0.106-0.670 ), personal-social abnormalities ( OR=0.321, 95%CI: 0.121-0.851 ) and neurodevelopmental abnormalities ( OR=0.353, 95%CI: 0.171-0.730 ) among puerparas with IPI of one year and greater as compared to those with IPI of less than one year, and no significant difference was seen in infant's neurodevelopmental abnormalities between puerparas with the first delivery and with IPI of less than one year.@*Conclusion@#IPI is associated with neurodevelopmental abnormalities among 6-month-old infants.

Specific blockade of muscle acetylcholine receptor by α-conotoxin MIA and MIB / 药学学报

The α-conotoxins are peptide toxins that are identified from the venom of marine cone snails and they hold outstanding potency on various subtypes of nicotinic acetylcholine receptors (nAChRs). nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, so nAChR dysfunctions have been involved in a variety of severe pathologies. Four types of α-3/5 conotoxins MI, MIA, MIB and MIC have been found from Conus magus. Among them, the activity and selectivity of MIA and MIB have not been well studied. In this study, four α-3/5 conotoxins MI, MIA, MIB and MIC were synthesized by solid peptide synthesis method, and the bioactivities of them were screened by double electrode voltage clamp electrophysiology. The results showed that MIA and MIB selectively inhibited muscle type acetylcholine receptors with IC50 values of 14.45 and 72.78 nmol·L-1, respectively, which are slightly weaker than MI and MIC. Molecular docking results have shown MIA and MIB interact with muscle-type nAChRs with similar mechanism. The reasons for activity differences may relate to the size of the N-terminal amino acids. Together, the conotoxins MIA and MIB may have the potential to develop as a tool for detect the function of muscle type nAChRs, as well as the diagnosis or treat of related diseases.

Correlation between hypersomnia and anhedonia in patients with major depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the correlation between hypersomnia and anhedonia in patients with major depressive disorder.Methods:From November 2018 to May 2019, patients hospitalized with major depressive disorder who met the ICD-10 diagnostic criteria were selected.According to the Epworth Sleepiness Scale (ESS), 46 patients were divided into daytime sleepiness group with ESS ≥ 7, and 171 patients were divided into non-sleepiness group with ESS < 7.The Chinese Revised Social Anhedonia Scale (RSAS) and the Chinese Revised Physical Anhedonia Scale (RPAS) were used to evaluate the patients' anhedonia symptoms.Two-way ANOVA and Pearson correlation analysis were used for data processing.Results:(1)There was no interaction between the hypersomnia and gender on the score of physical anhedonia ( F=0.274, P=0.601). The main effect analysis showed that there was significant difference in the influence of gender on physical anhedonia ( F=10.948, P<0.05). (2)There was interaction between the hypersomnia and age on the score of physical anhedonia ( F=4.396, P=0.013). Further simple effect analysis showed that the score of physical anhedonia in 40-49 age(21.54±12.37) was lower than that in 50-64 age(34.13±12.53) in daytime sleepiness group( P<0.05). (3) There was interaction between hypersomnia and sitting and lying on the score of social anhedonia ( F=4.247, P=0.041). Further simple effect analysis showed that the score of social anhedonia in patients with sitting and lying time less than 2 hours (13.71±5.18) was lower than that in patients with sitting and lying time more than 2 hours (19.75±6.39) in daytime sleepiness group( P<0.05). (4)Pearson correlation analysis showed that the total sleepiness score of depression patients was positively correlated with the social anhedonia score ( r=0.206, P<0.01). After adjusting for gender, age and sitting and lying time, the total sleepiness score was still positively correlated with the social anhedonia score( r=0.225, P<0.01). Conclusion:Hypersomnia may be associated with anhedonia in patients with major depressive disorder.

Research of the correlation between α1-antitrypsin and acute kidney injury after cardiopulmonary bypass / 中华胸心血管外科杂志

Objective:To figure out variety of the plasma level of Alpha-1-Antitrypsin(α1-AT) in patients who undergo AKI following cardiopulmonary bypass(CPB), and whether this biomarker serve as a competent predictor.Methods:We recruited 75 patients undergoing cardiac surgery with CPB from January 2018 to January 2019. Patients were categorized into two groups according to the development of AKI. The relationship between plasma concentration of α1-AT and renal injury in two groups was analyzed.Results:27 patients in the AKI group were aged (54.3±12.2)years old, including 15 males and 12 females, the time of cardiopulmonary bypass was(133.5±34.7)min. In the non-AKI group, 48 cases were aged(47.7±11.3)years old, including 26 males and 22 females, and the time of cardiopulmonary bypass was(133.5±34.7)min. α1-AT was significantly decreased in AKI group at 1 h after operation[(0.53±0.53)g/L vs. (1.46±0.91)g/L, P<0.05]compared with the non-AKI group. The sensitivity and specificity of α1-antitrypsin level at 1h after operation was the highest when α1-AT was 0.675 g/L. CPB time ( OR=5.890, 95% CI: 1.078-32.173) and age ( OR=4.427, 95% CI: 1.113-17.614) were independent risk factors for AKI after surgery, and α1-AT at 1h after CPB ( OR=0.084, 95% CI: 0.021-0.333) were protective factors after operation. Conclusion:Increased concentration of α1-AT after cardiopulmonary bypass at early time is a protective factor for AKI and the concentration of α1-AT in plasma could be used as an early biomarker of AKI after CPB.

Animal Model of Cystitis Based on Clinical Characteristics of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

Cystitis， one of the most common diseases in the urinary system， is manifested by urinary frequency， urinary urgency， and bladder pain， which are known as the classic symptom triad of bladder irritation， especially in women. In recent years， with the change of the lifestyle， the prevalence of bladder diseases in China is increasing year by year. According to the characteristics of etiology， pathogenesis， and clinical symptoms of cystitis， this paper listed the clinical diagnostic criteria in traditional Chinese medicine （TCM） and western medicine after consulting the relevant literature. Through the analysis of the existing animal model of cystitis， the fit between the model and clinical manifestations was evaluated， and the advantages and disadvantages were summarized. The models induced by "intraperitoneal injection of cyclophosphamide" and "Freund's complete adjuvant combined with bladder catheterization" were proved highly matched with manifestations despite some shortcomings such as long time and high cost. At present， the diagnostic criteria of cystitis are mainly based on western medicine， and the definitive diagnosis of the relevant types still depends on cystoscopy and tissue biopsy. The lack of TCM syndrome model limits the TCM research. Additionally， four diagnostic methods in TCM cannot be well applied to animal models because of the susceptibility to subjective factors. Behavioral tests can be used to determine the model index and develop the relevant behavior rating scale. Therefore， it is necessary to establish an animal model of cystitis in line with the clinical characteristics of western medicine and TCM syndrome differentiation， so as to better promote the study of cystitis.

Design, synthesis, and activity study of α-conotoxin A10LPnIA fluorescent probe / 药学学报

italic>α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems, and is closely related to a variety of neurological diseases and inflammation response. α-Conotoxin [A10L]PnIA, as an antagonist targeting α7 nAChR, plays an important role in studying the physiological and pathological processes involved in α7 nAChR. [A10L]PnIA was labeled with fluorescein 5-carboxytetramethylrhodamine, and the active peptide ([A10L]PnIA-F) was obtained by a two-step oxidative folding procedure in vitro. The Xenopus oocyte expression system and the two-electrode voltage clamp technique were used to identify the potency of [A10L]PnIA-F fluorescent peptide, and its cytotoxicity was detected by mouse macrophages and CCK8 method. The molecular weight of [A10L]PnIA-F fluorescent peptide was identified by mass spectrometry as 2 077.28 Da, which was consistent with the theoretical value. Electrophysiological determination of its half-maximal inhibitory concentration (IC50) for α7 nAChR is 17.32 nmol·L-1, which is consistent with [A10L]PnIA (IC50, 13.84 nmol·L-1). The cytotoxicity test results showed that within the concentration range of 5 nmol·L-1 to 10 μmol·L-1, there was no significant inhibition on the growth of mouse macrophages. The results showed that the α-conotoxin fluorescent probe [A10L]PnIA could provide pharmacological tools for the research of α7 nAChR-related neurophysiological and pathological mechanisms.

Mangiferin attenuates IL / 中南大学学报(医学版)

OBJECTIVES@#Chondrocyte apoptosis is an important process in the pathogenesis of osteoarthritis. Mangiferin exerts multiple pharmacological effects such as anti-inflammatory and anti-apoptosis. However, the role of mangiferin in chondrocyte apoptosis is not clear. In this study, we aimed to explore the role of mangiferin in IL-1β-induced chondrocyte apoptosis.@*METHODS@#ATDC5 cells were randomly divided into a control group, a IL-1β group, a MFN-L group, a MFN-M group, a MFN-H group and a MFN+LY294002 group. Cells in the control group were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN-L group, the MFN-M group and the MFN-H group were pretreated with 5, 10 and 20 μmol/L mangiferin for 1 h respectively, and then they were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN+LY294002 group were treated with LY294002 (25 μmol/L) for 1 h, then mangiferin (20 μmol/L) and IL-1β (10 ng/mL) for 1 h and 24 h, respectively. Cell viability was detected by CCK-8 assay and cell apoptosis was measured by flow cytometry. Colorimetric assay was conducted to measure the caspase-3 activity. The protein levels of Bcl-2, Bax, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway related proteins were detected by Western blotting.@*RESULTS@#Compared to the control group, cell viability was significantly decreased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly increased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly decreased in the IL-1β group (all @*CONCLUSIONS@#Mangiferin could attenuate IL-1β-induced apoptosis of the mice chondrocytes, which is mediated by the activation of PI3K/Akt signaling pathway.

Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation / 中华外科杂志

Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.

Study of quantitative flow ratio-guided surgical coronary revascularization / 上海交通大学学报（医学版）

Objective: To analyze the feasibility, safety and preliminary clinical results of quantitative flow ratio (QFR)-guided surgical coronary revascularization. Methods: From Jan 2018 to June 2019 at the Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, patients undergoing elective cardiac surgery with any coronary stenosis ≥ 50%, evaluated by preoperative coronary angiography visualization, were enrolled consecutively. There were 82 patients with 174 coronary artery vessels. Coronary artery bypass grafting (CABG) was recommended with a QFR value ≤ 0.8. The data of baseline characteristics, surgical procedure and perioperative outcomes were collected and analyzed. Results: QFR analysis was successfully carried out in 82 patients and 174 coronary artery vessels. QFR was detected positive ( ≤ 0.8) in 53 vessels (30.5%) and negative (>0.8) in the remaining 121 vessels (69.5%). As guided with QFR, 39 patients (47.6%) with 62 vessels (35.6%) proceeded to surgery for primary heart disease with concomitant CABG as planned, while the remaining 43 patients (52.4%) with 112 vessels (64.4%) changed revascularization strategy or spared CABG. Fifteen patients with simple coronary artery disease avoided CABG and discharged. Among the remaining 67 patients operated on, there were 2 deaths, 4 hemodialysis for new renal failure, 1 perioperative myocardial infarction and 1 stroke within 30 d. No unplanned revascularization was observed. The composite adverse events occurred in 6 cases (9.0%). Conclusion: QFR-guided surgical coronary revascularization is feasible and safe. This strategy could reduce the unnecessary bypass grafting. Further follow-up and prospective clinical trials are warranted to evaluate the effectiveness.

Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation / 中华外科杂志

Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.

Association of vitamin D and parathyroid hormone levels with glucose metabolism during pregnancy / 中华内分泌代谢杂志

Objective To explore the relationship between different statuses of vitamin D and parathyroid hormone (PTH) during pregnancy with glucose metabolism and the risk of gestational diabetes mellitus (GDM). Methods A total of 4138 pregnant women who had antenatal care in 3 hospitals of Hefei from March 2015 to December 2017 were recruited during 21-24 weeks. Baseline questionnaires were performed and serum 25-hydroxyvitamin D [25(OH) D] and PTH levels were measured in fasting venous blood. Glucose tolerance tests were performed during 24 to 28 weeks. Multivariate linear regression model and multivariate logistic regression model were applied to analyze the differences of glucose metabolism index and GDM risk among pregnant women at different statusesof25(OH)DandPTH.Results Theaveragelevelof25(OH)Dinthesecondtrimesterwas(39.8±16.6) nmol/L, with the median PTH 10.7 (6.9, 16.7) ng/L and the detection rate of GDM 20.4％. Covariance analysis showed no statistically significant association of vitamin D and PTH levels with glucose metabolism indexes. Pregnant women with high PTH and vitamin D deficiency had higher 1h postprandial plasma glucose ( 1hPG) , the area under the glucose curve ( AUCglu ) levels, and GDM risk compared with pregnant women with middle/lower PTH and vitamin D deficiency ( control group, all P<0.05) , and higher PTH accompanied with vitamin D non-deficiency ( Group 2, all P<0.05) . However, significant changes in glucose metabolism indicators and GDM risk were not observed in low-level PTH-pregnant women with vitamin D deficiency ( group 1) and group 2 pregnant women compared with control group. Conclusion There is an interaction between vitamin D/PTH levels and glucose metabolism during pregnancy. Vitamin D deficiency with elevated PTH level is associated with abnormal glucose metabolism.

Silencing Calreticulin Expression Inhibits Invasion Ability of SNK6 Cells in Vitro via Down-Regulating Expression of VEGF and MMP2/9 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of steadily down-regulating the expression of calreticulin (CALR) on the invasion of natural killer/T-cell lymphoma SNK6 cells, and explore its possible mechanism.@*METHODS@#The sequences of specific short hairpin RNA (shRNA) targeting on human CALR were designed, and were inserted into pLKO.1-puro lentivirus vector, and the reconbinant lentivirus vector was obtained; the lentivirus particles were backed by three-plasmid system and transfected into SNK6 cells, the SNK6 cells stably down-regulating the CALR expression were sercened by puromytain, the CALR-silencing effect was verified by real-time PCR and Western blot. CCK-8 assay was used to evaluate the cell viability, The transwell invasion assays was used to analyse invasion of SNK6 cells. The mRNA expression of Calreticulin, MMP2, MMP9 and VEGF was determined by real time PCR, the protein expression of Calreticulin and GAPDH was analyzed by Western blot.@*RESULTS@#The recombinant lentiviral vector pLKO.1-puro-shCALR was successfully constructed, packed into the lentivirus, then the SNK6 cells stably down-regulating Calreticulin expression was obtained. When Calreticulin was down-rengulated in SNK6 cells, the proliferation rate was reduced and the invasion ability was decreased; the mRNA levels of VEGF and MMP-2/9 also were reduced.@*CONCLUSION@#The stable down-regnlation of CALR expression in SNK6 cells can attenuate the imvasiveness of SNK6 cells, which maybe related with transcriptional decrease of MMP2, MMP9 and VEGF.

Cx43 silencing inhibits mechanical stress-induced apoptosis in mouse articular chondrocyte / 中南大学学报(医学版)

To explore the effect of connexin 43 (Cx43) silence on the apoptosis in mouse chondrocyte under mechanical stress.
 Methods: Mouse chondrocyte ATDC5 cells were divided into a control group, a mechanical stress group, a Cx43 siRNA transfection group, a scramble siRNA transfection group, a mechanical stress+scramble group, and a mechanical stress+siCx43 group. Flexcell FX-5000 system was used to produce mechanical stress on ATDC5 cells cultured in vitro. The mRNA and protein level of Cx43 was detected by quantitative RT-PCR (RT-qPCR) and Western blot. The cell activity and cell apoptosis was detected by cell counting kit-8 (CCK-8) method and flow cytometry, respectively. Caspase-3 activity was detected by colorimetric assay. The protein expression of Bcl-2, Bax, p-JNK and JNK was detected by Western blot.
 Results: Mechanical stress upregulated the mRNA and protein expression of Cx43 (both P<0.05). Transfection of Cx43 siRNA significantly decreased Cx43 mRNA and protein level (both P<0.05). After stimulation with mechanical stress, chondrocyte viability was significantly decreased, whereas cell apoptosis and caspase-3 activity were increased (both P<0.05). Mechanical stress obviously upregulated Bax protein level, and downregulated Bcl-2 protein expression and Bcl-2/Bax (both P<0.05). Cx43 siRNA transfection significantly increased cell viability, inhibited cell apoptosis and caspase-3 activity (both P<0.05). Cx43 siRNA also inhibited Bax expression, and increased the Bcl-2 protein expression and Bcl-2/Bax (both P<0.05). Furthermore, Cx43 siRNA significantly suppressed the p-JNK expression induced by mechanical stress (P<0.05).
 Conclusion: Cx43 silence inhibits mechanical stress-induced apoptosis in chondrocyte, which might be mediated by JNK signaling pathway.

Prospective cohort study on association between peri-conceptional air pollution exposure and gestational diabetes mellitus / 中华预防医学杂志

Objective@#To explore the association between the exposure to major air pollutants in pre-pregnancy and early pregnancy (peri-conceptional period) and gestational diabetes mellitus (GDM).@*Methods@#From March 2015 to April 2018, 4 817 pregnancies were recruited at three prenatal check-ups hospital in Hefei (Hefei First People′s Hospital, Hefei. Maternal and Child Care Hospital and the First Affiliated Hospital of Anhui Medical University), China. Questionnaire was used to collect the demographic data, the health status and lifestyle of pregnant women. GDM was diagnosed according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2017 Edition). Logistic regression was used to investigate the association of exposure to major air pollutants (PM2.5, PM10, SO2, CO and NO2) during different periods of pre-pregnancy (12 weeks before pregnancy) and first trimester (12 weeks after last menstruation) and duration of exposure to high levels of pollutants with GDM.@*Results@#The mean±SD of the age of subjects was (29.14±4.19) years old and the prevalence of GDM was 21.4% (n=1 030). The results of multivariate logistic regression analysis showed that after adjusting for confounding factors, the risk of GDM increased gradually with the prolonged exposure time of high-concentration pollutants compared with pregnant women who were not exposed to high pollution during the pre-pregnancy (χ2=61.28, Ptrend<0.001) with the OR (95%CI) values for exposure time of 1, 2, and 3 months about 1.42 (1.10-1.84), 1.73 (1.29-2.33), and 2.51 (1.75-3.59), respectively. In the pre-pregnancy period, in every 10 μg/m3 increase of PM2.5 and PM10, the OR (95%CI) values of GDM were 1.14 (1.08-1.20) and 1.13 (1.08-1.19), respectively; for each increase of 1 μg/m3 and 0.10 mg/m3 of SO2 and CO, the OR (95% CI) values of GDM were 1.03 (1.01-1.05) and 1.07 (1.01-1.13), respectively. For every 1 μg/m3 increase in the average concentration of SO2 in the first trimester, the OR (95%CI) value of GDM was 1.02 (1.01-1.05).@*Conclusion@#PM2.5, PM10, SO2 and CO exposure during the pre-pregnancy and SO2 exposure in first trimester were positively correlated with the risk of GDM.

Association between vitamin D level and lipid metabolism during second trimester / 中华流行病学杂志

Objective@#To explore the relationship between the vitamin D levels and lipid metabolism during second trimester.@*Methods@#A total of 1 875 pregnant women who were in the second trimester and had antenatal care in 3 hospitals in Hefei of Anhui province from March 2015 to February 2018 were included. Baseline questionnaire survey was performed, and fasting venous blood samples were collected from the pregnant women to detect serum 25(OH)D, cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. Cubic non-linear model and linear regression model were used to analyze the linear relationship between vitamin D levels and lipid metabolism indicators in the second trimester.@*Results@#The vitamin D deficiency rate was 75.3% (1 412/1 875) in the pregnant women. The mean levels of lipid metabolism indicators TC, TG, HDL-C and LDL-C were (233.22±38.87), (226.24±83.88), (79.04±12.77), and (109.54±25.95) mg/dl respectively. Multivariate linear regression model results showed, compared with Q5 of the 25(OH)D, the TC and TG levels of Q1-Q4 groups significantly increased, and the LDL-C of Q1 and Q2 groups significantly increased. The highest difference between TC, TG and LDL-C was observed in Q1 group. (TC: β=16.88, 95%CI: 10.50-23.26; TG: β=34.92, 95%CI: 21.32-48.53; LDL-C: β=9.06, 95%CI: 4.77-13.35). No significant differences in HDL-C level among the 5 groups were observed. When stratified with vitamin D deficiency the results showed that, when 25(OH)D was <50 nmol/L, TC, TG and LDL-C levels decreased by 3.53 (95%CI: 1.30-5.75), 7.42 (95%CI: 2.41 to 12.44) and 2.08 mg/dl (95%CI: 0.60-3.57) along with a 10 nmol/L increase of 25(OH)D, the difference was statistically significant, and when 25(OH)D was ≥50 nmol/L, no significant correlation was found between 25(OH)D level and TC, TG and LDL-C levels. No significant relationship between 25(OH)D level and HDL-C level was observed regardless of vitamin D deficiency.@*Conclusions@#There was a nonlinear relationship between vitamin D levels and lipid metabolism indicators in the second trimester. There was a significant negative correlation between 25(OH)D level and lipid metabolism indicators only in the deficiency of vitamin D.

The association of Vitamin D levels with lipid metabolism during pregnancy / 中华预防医学杂志

Vitamin D deficiency is common in pregnant women, and it is associated with multiple gestational complications, fetal intrauterine dysplasia, and maternal and infant health in postpartum period. Vitamin D involved in lipid metabolism may affect maternal-fetal health during pregnancy through this biological pathway. This review provides an overview of three main aspects, including, the effect of vitamin D on the mechanism of lipid metabolism, the relationship between vitamin D and lipid metabolites in pregnant women and women with pregnancy complications. An association between vitamin D status and lipid metabolism at different stages of pregnancy has been justified in most current studies, and the underlying mechanism has also been partly elucidated. Given some gestational complications, such as gestational diabetes and pre-eclampsia, pregnant women with these conditions are often associated with abnormal lipid metabolism and vitamin D deficiency. There is no doubt that the studies on the vitamin D supplementation and lipid metabolism improvement could have crucial clinical significance for this population. More randomized controlled trials with multi-center, large sample and multi-dose interventions are needed in the future to provide scientific evidence for clinical practice.