Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L / 药学学报

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Computational Study of Fenestration and Parallel Grafts Used in Aortic Arch Lesion / 医用生物力学

Objective To explore hemodynamics of the aortic arch and supraarch vessels after thoracic endovascular aortic repair with fenestration and parallel grafts techniques, and compare the differences of these techniques. Methods Four patients with aortic arch lesions whose supraarch vessels were reconstructed by different surgical techniques (fenestration, chimney and periscope) were studied, and three-dimensional (3D) geometric models were established based on postoperative image data. The physiological flow obtained from two dimensional (2D) phase contrast magnetic resonance imaging were imposed on the ascending aorta inlet and the supraarch vessels outlets. The pressure waveform of 3-element Windkessel model was imposed on the descending aorta outlet. Through computational fluid dynamics ( CFD ) simulations, the hemodynamic parameters were obtained, including the pressure of supraarch vessels, the velocity vector of the stent inlet, and the relative residence time. Results The pressure change of the periscope stent was the largest, followed by the fenestration stent, and the pressure change of the chimney stent was the smallest. The velocity of the fenestration and periscope stent inlet was uneven, which might form vortex. The velocity of the chimney stent inlet was even. The high relative residence time concentrated in distal end of the fenestration stent outer wall, the ‘gutter’ part, and the place where the chimney and periscope stent adhered to the vessel wall. Conclusions The pressure difference between the inner and outer walls of the fenestration and periscope stent was high, so it was recommended to use the balloon-expandable stent. The pressure difference between the inner and outer walls of the chimney stent was low, so it was recommended to use the self-expanding stent. The predicted location of thrombosis was consistent with the clinical follow-up data, so it may be used for surgical planning and risk assessment of interventional treatment of aortic arch lesions.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Otologic disorders and management strategies in Turner syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the incidence and risk factors of otologic disorders in patients with Turner syndrome (TS), so as to provide management strategies for ear health. Methods: This study is a prospective study based on questionnaires and a cross-sectional study. The TS patients who visited our hospital from 2010 January to 2021 March were included (A total of 71 patients with TS were included in this study. the age of TS diagnosed was 3- to 11-year-old, age of visiting ENT department was 4- to 27-year-old) and the incidence of otologic diseases in different age groups was investigated by questionnaires. The cross-sectional study included ear morphology and auditory function assessment, and further analysis of the risk factors that related to ear disease. Prism was used for data analysis. Results: The investigation found that the incidence of acute otitis media in patients aged 3-6 and 7-12 years was higher than that of patients over 12 years old, which was 33.8%(24/71), 42.9%(30/70)and 23.5%(8/34), respectively; 21.1% (15/71) of patients were recurrent acute otitis media in patients aged 3-6 years, and about 46.6% (7/15)of them persisted beyond 6-year. The prevalence of otitis media with effusion in the three groups was 32.4%(23/71), 34.3%(24/70)and 38.2%(13/34), respectively; the recurrence rate of tympanocentesis was 100%(7/7), 42.9%(3/7)and 50.0%(1/2), which was significantly higher than that of grommet insertion. For age groups of 3-6 and 7-12 years, the prevalence of acute otitis media and secretory otitis media was lower in the X chromosome structure abnormal patients; while for patients older than 12 years, otitis media with effusion was the highest prevalence in Y-chromosome-containing karyotypes. In addition, the prevalence of acute otitis media and otitis media with effusion in patients with other system diseases were increased significantly. A cross-sectional study found that 7.0% (5/71)of the lower auricular, 4.2% (3/71)of the external auditory canal narrow, and 38.0% (27/71)of the tympanic membrane abnormality. 35.2%(25/71) had abnormal hearing, including 17 cases of conductive deafness, 6 cases of sensorineural hearing loss, and 2 cases of mixed deafness. The rest of the patients had normal hearing, but 6 of them had abnormalities in otoacoustic emission. Eustachian tube function assessment found that the eustachian tube dysfunction accounted for 38%(27/71). Hearing loss and abnormal Eustachian tube function were not significantly related to karyotype(Chi-square 2.83 and 2.84,P value 0.418 and 0.417), but significantly related to other system diseases(Chi-square 13.43 and 7.53,P value<0.001). Conclusions: The incidence of TS-related otitis media and auditory dysfunction is significantly higher than that of the general population. It not only occurs in preschool girls, but also persists or develops after school age. Accompanied by other system diseases are risk factors for ear diseases. Clinicians should raise their awareness of TS-related ear diseases and incorporate ear health monitoring into routine diagnosis and treatment.

Effect of Danggui Niantongtang on Expression of Autophagy-related Proteins LC3， Beclin1 and p62 in Rats with Adjuvant Arthritis Differentiated into Wind-damp-heat Impediment / 中国实验方剂学杂志

ObjectiveTo observe the preventive and control effects of Danggui Niantongtang against adjuvant arthritis differentiated into wind-damp-heat impediment in rats and its influences on the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 （LC3）， homolog of yeast Atg6 （Beclin1） and p62. MethodThe six-week-old male SD rats were randomly divided into the normal group， wind-damp-heat impediment model group， low-， medium-， and high-dose Danggui Niantongtang （5.67， 11.34， 22.68 g·kg-1） groups， and methotrexate （MTX， 1.35 mg·kg-1） group， with 10 rats in each group. A rat model of adjuvant arthritis was established by subcutaneous injection of inactivated Mycobacterium tuberculosis into the tail root， followed by exposure to the manual climatic box for 16 d for inducing the wind-damp-heat impediment. The drugs were administered intragastrically on the day of immunization for 28 d. The general conditions of rats were observed and the swelling degree of toes and arthritis index （AI） were detected. The pathological changes in the synovial tissues of the knee joints were observed by hematoxylin-eosin （HE） staining. The mRNA expression levels of LC3， Beclin1， and p62 in the synovial tissues were measured by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， followed by the assay of their protein expression by Western blot and immunohistochemistry. ResultCompared with the normal group， the wind-damp-heat impediment model group exhibited significantly increased swelling degree of toes （P<0.01）， increased AI （P<0.01）， proliferated synovial cells （P<0.01）， up-regulated LC3 and Beclin1 protein and mRNA expression （P<0.01）， and down-regulated p62 protein and mRNA expression （P<0.01） after 16， 20， 24， 28-d medication. Compared with the wind-damp-heat impediment model group， each medication group displayed alleviated toe swelling and synovial hyperplasia to different degrees， decreased mRNA and protein expression levels of LC3 and Beclin1 （P<0.01）， and increased p62 mRNA and protein expression （P<0.05，P<0.01）， with the best outcomes observed in the medium-dose Danggui Niantongtang group. ConclusionDanggui Niantongtang effectively relieves adjuvant arthritis due to wind-damp-heat impediment in rats， which may be related to its regulation of the expression of autophagy-related proteins LC3， Beclin1， and p62 and the inhibition of autophagy.

Effect of Danggui Niantongtang on Autophagy and Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocyte / 中国实验方剂学杂志

ObjectiveTo explore the effect of Danggui Niantongtang （DGNTT） on cell apoptosis and autophagy in rheumatoid arthritis （RA） fibroblast-like synoviocytes （FLS）. MethodRA-FLS were isolated and cultured from the synovial tissue of RA patients. The cells were treated with 10% blank serum （blank control group）， 10% sera containing low， medium and high doses of DGNTT. Wound healing assa and cell invasion test were applied to observe the effect of RA-FLS invasion technique. The apoptosis and autophagy level of RA-FLS cells was detected by Hoechst33342 method and monodansylcadaverine （MDC） staining. The mRNA and protein expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， microtubule-associated protein 1 light chain 3 （LC3）， autophagy key molecular yeast Atg6 homolog 1 （Beclin1） were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）and Western blot. ResultCompared with the blank control group，each dose of serum could slow down the wound healing and significantly Reduce the number of RA-FLS cells invading the lower chamber（P<0.01），the mRNA and protein expression levels of Bcl-2，LC3，Beclin1 were significantly decreased（P<0.01）， and Bax were significantly increased（P<0.01）. Hoechst33342 results showed that low， medium and high doses DGNTT could promote RA-FLS cell apoptosis. After MDC staining，autophagosome in low， medium and high doses DGNTT decreased significantly（P<0.01）. ConclusionDanggui Niantongtang can effectively inhibit the proliferation of fibroblast-like synoviocytes. Its mechanism may be related to promote apoptosis and inhibit autophagy of fibroblast-like synoviocytes.

Clinical outcomes of severe calcified lesions after carotid artery stenting / 中华普通外科杂志

Objective:To evaluate the safety and efficacy of carotid artery stenting (CAS) in the treatment of non-circumferential severe calcification using the distal embolic protection device.Methods:Clinical data of patients with severe calcification lesions in cervical carotid artery treated by CAS from Jan 2018 to Dec 2020 at our center was analyzed retrospectively.Results:226 consecutively admitted patients of cervical carotid artery stenosis and non-circumferential severe calcification (CR>270°) underwent CAS using the distal embolic protection device. The technical success rate was 90.26%. No death or myocardial infarction occurred during the perioperative period. Two patients had ipsilateral hemiparesis ischemic stroke during post-dilatation. The incidence of perioperative bradycardia/hypotension was 25.34%. Patients were followed up for 6-36 months, with median follow-up period of 17.3 months. The incidence of mild or moderate in-stent restenosis (<70%) was 16.59%, and the incidence of severe in-stent restenosis or occlusion (>70%) was 3.22%.Conclusions:For carotid artery stenosis with non-circumferential severe calcification in high risk for CEA patients, carotid artery stenting is safe and effective with the aggressive pre-dilation strategies, strict stent selections and implantation standards. The incidence of perioperative death, myocardial infarction or ipsilateral hemiparesis ischemic stroke was low. The patency rate of the carotid stent in the calcification lesion is satisfactory during the mid-term follow-up.

Role of Foxo6 in insulin resistance of vascular endothelial cells induced by high glucose and high fat and its interaction with NF-κB pathway / 中国药理学通报

Aim To investigate the expression of Foxos in human umbilical vein endothelial cells(HUVECs)with insulin resistance(IR)induced by high glucose and high fat(HG/HF)stress and its significance.Methods First, the IR model of endothelial cells was established by HG /HF stress.The differential expression of Foxos gene in normal(Ctrl )group and HG /HF group was observed, and the subtypes with the most significant changes in Foxos were screened out, such as Foxo6.Next, Foxo6 was silenced to observe its role in endothelial cell with IR.Finally, whether the mechanism of Foxo6-mediated IR was related to the interaction of NF-κB signaling was investigated.Results The expression increase of Foxo6 was the most significant among Foxos under the IR condition induced by HG/HF.Using a small RNA interference and plasmid transfection technique, we found that the silence effect of the siRNA3 fragments targeting Foxo6 was the most significant among the siRNAs.Moreover, the further study showed that silencing the Foxo6 gene could significantly reverse the endothelial IR induced by HG/HF, and the mechanism of the reversal effect was related to the interaction between the Foxo6 and NF-κB signal.Conclusions Foxo6 mediates the endothelial cell IR induced by the HG /HF stress.The underlying mechanism is that Foxo6 can interact with NF-κBp65 and activate NF-κB signaling pathway.Silencing Foxo6 can improve the IR of vascular endothelial cells induced by HG /HF stress.

Effect of Danggui Niantongtang on Key Factors of Extrinsic and Intrinsic Apoptotic Pathway in Synovial Tissue of Adjuvant Arthritis Rats / 中国实验方剂学杂志

Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis （AA） rats， and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats， including its body weight， were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 （Fas）， Fas-associating protein with a novel death domain（FADD）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase Caspase-3 （Caspase-3） were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the normal group， the toe volume of the model group increased significantly （<italic>P</italic><0.01）， with significantly proliferated synovial cells， significantly reduced mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 in synovial tissues（<italic>P</italic><0.05，<italic> P</italic><0.01）， and significantly increased Bcl-2 level （<italic>P</italic><0.01）. Compared with the model group， the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated （<italic>P</italic><0.01）， with significantly improved synovial hyperplasia， significantly increased mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 （<italic>P</italic><0.05， <italic>P</italic><0.01）， and significantly decreased expression levels of bcl-2 mRNA and protein （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas， FADD， Bax， Bcl-2 and Caspase-3， and promoting the apoptosis of synovial cells.

Rutaecarpine exerted anti-osteroporosis / 药学学报

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg-1·day-1) and high-dose RUT group (45 mg·kg-1·day-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

Short term result of COOK-ZFEN custom-made endovascular stent graft system for the treatment of short-neck abdominal aortic aneurysm / 中华普通外科杂志

Objective:To evaluate the safety and efficacy of a Zenith fenestrated aortic stent-graft (ZFEN) system in the treatment of short-necked aneurysms.Methods:The clinical data of 5 patients receiving F-EVAR in Zhongshan Hospital, Fudan University from Mar 2018 to Sep 2019 according to the standards of short-necked abdominal aortic aneurysm and COOK ZFEN custom stent were retrospectively analyzed.Results:Patients' average age was (69±11) years old. The time of stent customization was 4-6 weeks. The average maximum diameter of AAA was (60.8±14.0) mm. The average proximal neck diameter was (26.0±2.6) mm and the average length anchoring zone was (6.4±2.2) mm. The rate of technical success was 100%. There was no intraoperative loss of visceral vessels and stent displacement. The meane follow-up time was 6.8 months. The perioperative mortality was 0, and there were no other major complications. There were 3 patients with simple type Ⅱ endoleak and 1 patient with type Ⅲ endoleak. The endoleaks disappeared in 4 patients during follow-up of 3-12 months. 1 patient suffered with type Ⅱ and type Ⅲ endoleak, and the visceral vessels and branching stents were patent in all patients.Conclusion:The short term result of COOK ZFEN stent-graft system was safe and feasible for the treatment of short-necked AAA.

Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia / 中华外科杂志

The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.

Investigation of risk factors for gastric cancer in Hanzhong area and establishment of a gastric cancer risk prediction model based on gastric function index / 公共卫生与预防医学

Objective To investigate the risk factors of gastric cancer in Hanzhong area and establish a gastric cancer risk prediction model based on gastric function indexes. Methods A questionnaire survey was conducted on 227 patients with gastric and non-gastric cancer admitted to the Department of Gastroenterology of Hanzhong Central Hospital from January 2018 to January 2019. The diet, lifestyle habits, family history, and past history of the subjects were collected. Serological tests (including serum PGⅠ,Ⅱ, and G-17), gastroscopy and pathological examination of the samples were carried out. Multi-factor Logistic regression analysis was performed to analyze the high risk factors. The efficacy of serum gastric function for gastric cancer screening was assessed through ROC curve. Results There were no significant differences in the distribution of age (χ2=0.054, P=0.816), gender (χ2=3.823, P=0.051) and BMI (χ2=5.569, P=0.135) between the gastric cancer and non-gastric cancer groups, suggesting that the clinical data between the two groups was comparable. Multivariate logistic regression analysis showed that smoked food intake (P=0.031, 95% CI: 1.150 ~ 17.545) and hyperlipidemia (P=0.039, 95% CI:0.216~0.960) were high risk factors for gastric precancerous lesions, other factors did not show significant high risk (P>0.05). The results of ROC curve showed that the diagnostic efficacy of combined PG I, PG II, and G-17 was significantly higher than that of PG I, PGⅡ, or G-17 alone (P<0.05). Conclusion The risk factors of gastric cancer in Hanzhong area mainly included the intake of smoked food and hyperlipidemia. Patients can be advised to pay attention to diet during clinical treatment. Based on gastric function indexes PG, PGⅡ and G-17, the diagnosis of gastric precancerous lesions had a good prediction. The combined diagnosis is more effective, which provided a theoretical basis for the early diagnosis of clinical gastric cancer.

Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF / 神经科学通报·英文版

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines / 神经科学通报·英文版

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester.@*METHODS@#A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 μmol/L), marginal deficiency (0.70-<1.05 μmol/L), and sufficiency (≥1.05 μmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 μmol/L), marginal deficiency (0.35-<0.70 μmol/L), and sufficiency (≥0.70 μmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio.@*RESULTS@#The average retinol concentration of the pregnant women was (1.15±0.30) μmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) μmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (pm=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (pm= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001).@*CONCLUSION@#There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia / 中华外科杂志

@#The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.

Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia / 中华外科杂志

The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.

Advances in the study of T cell immunity in invasive fungal infections secondary to sepsis / 上海交通大学学报（医学版）

Invasive fungal infections (IFI) has high morbidity and mortality. It is more common in hospital infections, and especially in sepsis, the risk of secondary IFI is increased. Immunosuppression of sepsis may affect immune function of T cells, and various T cells subsets have different effects on various fungal pathogens of IFI. The review discusses the pathophysiological processes, mechanism and therapeutic methods of T cell immunity in IFI secondary to sepsis, in order to summarize the role of T cells in IFI secondary to sepsis and introduce the new immunotherapy.