Validation of compound C19 as a glutaminase C inhibitor / 药学学报

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

Risk factors of perinatal complications in patients with pulmonary hypertension underwent cesarean section in 4 Chinese centers / 中华心血管病杂志

Objective: To identify the risk factors related to perinatal complications in patients with pulmonary hypertension underwent cesarean section. Methods: We retrospectively analyzed the medical records of all pregnant women with pulmonary hypertension hospitalized in 4 different hospitals in Shandong province and underwent cesarean section between May 2010 and May 2020. Patients were divided into perinatal complication group and control group according to the presence or absence of perinatal complications. Perinatal complications included aggravated heart function, new onset arrythmias, sudden cardiac arrest, all-cause death within 42 days post cesarean section, postpartum bleeding and thrombotic events. Risk factors of perinatal complications were analyzed. Results: A total of 167 patients (47 cases in the perinatal complication group and 120 cases in the control group) were included in this study. The average age of this cohort was 28(24, 32) years, and 75(44.9%) patients suffered newly diagnosed pulmonary hypertension during pregnancy. The main cause of pulmonary hypertension was congenital heart disease (137(82.0%)). Age, pregnant weeks, percent of primipara, intra-cardiac shunt, and receiving targeted medication therapy, cardiac dimensions were similar between the two groups. A total of 62 complications were recorded in the complication group including 28 cases of aggravated heart function, 4 cases of new onset arrythmias, 2 cases of cardiac arrest, 11 cases of bleeding or thrombotic events and 17 patients were dead. Prevalence of idiopathic pulmonary hypertension and general anesthesia was significantly higher, functional capacity was significantly lower in perinatal complication group than in control group (all P<0.05). The estimated systolic pulmonary artery pressure, serum N-terminal pro-B type natriuretic peptide and total bilirubin (TBIL) levels were significantly higher in perinatal complication group than in control group (all P<0.05). Logistic analysis demonstrated WHO Function Class(FC) Ⅲ/Ⅳ (OR=2.416,95%CI 1.016-5.743, P=0.046) and TBIL level (OR=6.874,95%CI 1.643-28.757, P=0.008) were the independent risk factors of perinatal complications. Conclusion: TBIL and WHO FC are independent risk factors of perinatal complications in pregnant women with pulmonary hypertension underwent cesarean section.

Predictive value of plasma TMAO combined with NT-proBNP on the prognosis and length of hospitalization of patients with ischemic heart failure / 中华心血管病杂志

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.

Effect of Yiqi Fuzheng Jiedu Decoction on Autophagy and Growth of A549 Cells： An Exploration Based on p53/AMPK Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of Yiqi Fuzheng Jiedu decoction （YQFZJDD） on autophagy and growth of A549 cells. Method:A549 cells were intervened with YQFZJDD-containing serum prepared in advance. The levels of microtubule-associated protein 1 light chain 3 （LC3）， homologue of yeast autophagy-related gene 6 （Beclin1）， p62， p53， adenosine 5'-monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mammalian target of rapamycin （mTOR）， and phosphorylated mTOR （p-mTOR） were detected by Western blot assay， and microtubule-associated protein 1A/1B light chain 3B （MAP1LC3B） by immunofluorescence （IF） assay. The proliferation， invasion， and senescence of A549 cells were separately measured by 5-ethynyl-2'-deoxyuridine （EDU） staining， Transwell assay， and <italic>β</italic>-galactosidase staining. In the presence of autophagy inhibitor 3-methyladenine （3-MA， 5 mmol·L^-1）， the cells were divided into the 10% fetal bovine serum （blank） group， 10% control serum （control） group， low-， medium-， and high-dose 10% YQFZJDD-containing serum groups， and high-dose 10% YQFZJDD-containing serum + 3-MA group， followed by the measurement of A549 cell proliferation， invasion， and senescence. In the adoption of p53 inhibitor Pifithrin-<italic>α</italic> （PFT-<italic>α</italic>， 10 μmol·L^-1）， the cells were divided into the control group， PFT-<italic>α</italic> group， high-dose YQFZJDD-containing serum group， and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group. Then the LC3-Ⅱ and Beclin1 expression， MAP1LC3B fluorescence intensity， as well as A549 cell proliferation， invasion and senescence were determined. Result:Compared with the blank group and control group， YQFZJDD-containing serum at the medium and high doses up-regulated the protein expression levels of LC3-Ⅱ and Beclin1 in A549 cells after 48-h intervention in a dose-dependent manner （<italic>P</italic><0.01）. Besides， YQFZJDD-containing serum at the low-， medium-， and high-doses down-regulated p62 and p-mTOR/mTOR expression （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated p53 and p-AMPK/AMPK （<italic>P</italic><0.01）， decreased the number of proliferative and invasive cells， increased the number of senescent cells （<italic>P</italic><0.01）， and enhanced the IF intensity of MAP1LC3B， with the optimal effect observed in the high-dose YQFZJDD-containing serum group （<italic>P</italic><0.01）. Compared with the high-dose YQFZJDD-containing serum group， the high-dose YQFZJDD-containing serum + 3-MA group and high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group exhibited significantly increased proliferative and invasive cells but decreased senescent cells （<italic>P</italic><0.05， <italic>P<</italic>0.01）. Meanwhile， the IF intensity of MAP1LC3B in the high-dose YQFZJDD-containing serum + PFT-<italic>α</italic> group was weakened and the LC3-Ⅱ and Beclin1 protein expression levels declined （<italic>P</italic><0.05， <italic>P<</italic>0.01）. Conclusion:YQFZJDD promotes the autophagy of A549 cells through the p53/AMPK signaling pathway to inhibit their proliferation， invasion and migration but accelerate senescence， thus playing a crucial role in inhibiting the progression of lung cancer.

Allopregnanolone protecting cell line SH-SY5Y against 6-hydroxydopamine-induced lesion / 解剖学报

Objective To clarify the protective effect of allopregnanolone (APα) on cell line SH-SY5Y damaged by 6-hydroxydopamine (6-OHDA) and its possible molecular mechanism. Methods 6-OHDA, APα, γ-aminobutyric acid A receptor (GABAAR) antagonist, voltage-gated L-type Ca2

The value of ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy in patients with COVID-19 / 中华急诊医学杂志

Objective:To assess the value of the ROX index in evaluating the efficacy of high-flow nasal cannula oxygen therapy (HFNC) in patients with coronavirus infected disease (COVID-19).Methods:This is a retrospective study. The included patients were diagnosed as COVID-19 in the intensive care unit (ICU) of the Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 15, 2020 to March 15, 2020. All the patients were treated by HFNC. According to whether the patient subsequently received non-invasive positive pressure ventilation or invasive positive pressure ventilation, patients were divided into the HFNC success group and the HFNC failure group. Parameters in the two groups such as basic characteristics, lactic acid, number of chest radiographs, APACHE II, lymphocyte count, baseline respiratory rate, baseline percutaneous oxygen saturation, baseline PaO 2/FiO 2, baseline ROX index, and ROX index after 2, 6 and 12 h HFNC treatment were analyzed with t test, Chi-square test or rank sum test. Results:A total of 57 cases were included in this study. There were no significant differences in sex, age, comorbidities, lactic acid, quadrants of chest radiograph lung infection, APACHE II, lymphocyte count, and baseline respiratory frequency, transcutaneous oxygen saturation, oxygenation index, and ROX index between the HFNC success group and the HFNC faliure group ( P>0.05). Logistic regression analysis showed that ROX index after 2 h HFNC treatment ( OR=0.069), ROX index after 6 h HFNC treatment ( OR=0.194) and ROX index after 12 h HFNC treatment ( OR=0.036) were all protective factors for the therapeutic effect of HFNC treatment in COVID-19 patients. ROC curve showed that there were significant differences in ROX index after 2 h HFNC treatment, ROX index after 6 h HFNC treatment, and ROX index after 12 h HFNC treatment ( P<0.05). In the evaluation index, the area under the ROC curve of the ROX index after 2 h HFNC treatment was 0.838, the sensitivity was 64.5%, and the specificity was 100%. After 6 h HFNC treatment, the area under the ROX index ROC curve was 0.762, the sensitivity was 64.5%, and the specificity was 92.3%. After 12 h HFNC treatment, the ROX index ROC curve area was 0.866, the sensitivity was 67.7%, and the specificity was 100%. Conclusions:The ROX index can be used to evaluate the efficacy of HFNC in COVID-19 patients in a timely, simple and real-time manner.

Pathological Observation of Blood Stasis Syndrome in Non-diabetic Peripheral Neuropathies: A Retrospective Analysis Based on Nerve Biopsy / 中国结合医学杂志

OBJECTIVE@#To investigate the pathological features of blood stasis syndrome (BSS) in non-diabetic peripheral neuropathy.@*METHODS@#Clinical data of 31 patients with non-diabetic peripheral neuropathy who had undergone nerve biopsy during December 2004 and December 2010 in Xuanwu Hospital Capital Medical University were retrospectively analyzed. According to Chinese medicine (CM) syndrome differentiation and signs, 26 patients were blood stasis type and 5 patients were non-blood stasis type. Clinical and pathological data were compared in detail.@*RESULTS@#Clinically, although both groups shared similar symptoms of limb numbness, weakness and sensory disturbances, the prevalence of neuralgia was much grievous in BSS group (73.1%, 26/31) compared with the non-BSS group (0%, 0/5). As for signs, dermal nutrients disturbance (84.6%, 22/26), dark or purple tongue (100.0%, 26/26), and sublingual varices (80.7%, 21/26) were more common in the BSS group than the non-BSS group (0%, 60%, 20%, respectively). The prevalence of qi deficiency cases (19/26) in the BSS group was significantly higher compared with the non-BSS group (1/5). The unique histological manifestations of BSS were axonal degeneration (16/26 vs 2/5 in non-BSS group), which was the hallmark of ischemia. Cases with BSS had prominent microangiopathy (61.5%, 16/26), manifested as epineurium vasculitis (inflammatory cell infiltrated to the vessel wall, obliteration and recanalization, vascular proliferation, extravascular hemosiderin deposition), angiotelectasis, proliferation and hyaline degeneration of endoneurium capillary. In the BSS group, impaired blood-nerve barrier was indicated by sub-perineurial edema (46.2%, 11/26) and endoneurial edema (15.4%, 4/26). The Renaut body (15.4%, 4/26) and amyloid deposition (3.8%, 1/26) found in the BSS group were absent in the non-BSS group.@*CONCLUSIONS@#BBS was common in non-diabetic peripheral neuropathies. The nerves exhibited ischemic alteration of primary axon degeneration and secondary demyelination. The interstitial tissue revealed microcirculation impairment, blood-nerve barrier disturbance, amyloid deposition and proliferation changes. The high prevalence of qi deficiency also highlights the therapy of promotion of blood circulation and removal of blood stasis.

Allopregnanolone restores dopaminergic neurons and motor performance in Parkinson’s disease mice and its molecular mechanisms / 解剖学报

[ Abstract] Objective To investigate the effects of allopregnanolone (APα) on the dopaminergic neurons in substantia nigra, striatal dopaminergic neural fibers and behavioral performance in Parkinson’ s disease (PD) model mice, as well as its possible molecular mechanisms. Methods C57BL / 6 adult male mice with 20-25 g at 3-month old (n = 90) were successively injected with 6-hydroxydopamine (6-OHDA) to generate a PD animal model. APα and its receptor γ-aminobutyric acid A receptor (GABAAR) antagonist—bicuculline (Bic) were successively injected. ELISA was used to detect the APα or dopamine concentration in the serum, cerebral cortex and striatum. The number of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatal dopaminergic neural projections were examined by immunohistochemical staining. The expression levels of GABAAR in membrane fractions and Ca

Effect of Modified Ditantang on Autophagy and Relevant Proteins in Brain Cells of Rats with Cerebral Ischemia Reperfusion Injury / 中国实验方剂学杂志

Objective:To investigate the effect of modified Ditantang on autophagy and relevant proteins in brain cells of rats with cerebral ischemia reperfusion injury. Method:The cerebral ischemic reperfusion (CIR) injury model in rats was built by reversible middle cerebral artery occlusion artery suture of middle cerebral embolism method, and randomly divided into sham group, model group, high-dose modified Ditantang group(H-dose), low-dose modified Ditantang group (L-dose, 0.384 g·kg-1) and PLXT group (0.1 g·kg-1). Sham and model groups were given normal saline by gastric perfusion, H-dose and L-dose groups were given modified Ditantang, and the PLXT group were given Piracetam tablets, intragastric volume 10 mL·kg-1. The treatment lasted for 7 d. Within 24 hours after administration, the histopathological examination was performed, the volume of cerebral infarction, neuronal apoptosis and serum levels of inflammatory factors were compared, and the expressions of autophagy related microtuble-associated protein 1 light chain 3(LC3)Ⅱ, Beclin1, B-cell lymphoma-2(Bcl-2) and p62 in brain tissues were determined. Result:Cells and blood vessel necrosis, neuron swelling and interstitial edema were observed in model group, a few neurons died, edema was reduced, swelling of nerve cells was alleviated in H-dose, L-dose and PLXT groups. The volume of cerebral infarction and neuronal apoptosis in H-dose, L-dose and PLXT groups were lower than those in model group (Pα, intedeukin (IL)-2 and IL-8 in H-dose, L-dose and PLXT groups were lower than those in model group (PPConclusion:Modified Ditantang can improve brain injury and interfere with autophagy after MCAO/R, alleviate inflammation, and regulate autophagic activity, which may be related to the down-regulation of expressions of LC3 Ⅱ, Beclin1 and the up-regulation of expression of p62.

MicroRNA-182 down-regulates the expression of MTSS1 and promotes the migration and metastasis of three-negative breast cancer / 医学研究生学报

Objective The up-regulated expression of miR-182 is associated with poor prognosis of triple-negative breast cancer. This study explored the biological function of the miR-182/MTSS1 signaling pathway in three-negative breast cancer (TNBC) and the mechanism of its regulation. Methods The relative quantitative expressions of miR-182 and MTSS1 were detected in the cancerous and adjacent tissues of 30 cases of TNBC, the influence of miR-182 and MTSS1 on the proliferation and invasiveness of the cells evaluated by cell function tests, the potential binding sites of miR-182 to MTSS1 predicted with the Targetscan software, and MTSS1 confirmed to be the target gene by the dual luciferase reporter system. After transfection of miR-182 into the MCF-7 cells, RT-PCR and Western blot were used to determine the gene and protein expressions of MTSS1 and verify the regulatory effect of miR-182 targeting MTSS1. Results The expression of miR-182 was significantly higher (t=-8.409, P=0.000), while that of MTSS1 lower in the cancerous than in the adjacent tissue (t=2.961, P=0.006). The over expression of miR-182 and silenced expression of MTSS1 markedly enhanced the proliferation and migration of the MCF-7 cells compared with those of the control (P<0.01), while inhibition of miR-182 and over expression of MTSS1 remarkably suppressed their proliferation and migration of the MDA-MB-231 cells (P<0.01). The base sequences of 1083-1089 of the MTSS1 gene were confirmed to be the target binding sites of miR-182. After transfection of miR-182, the expression of MTSS1 in the MCF-7 cells was significantly down-regulated as compared with that in the control (t=-5.918, P= 0.027). Conclusion Target binding of miR-182 to MTSS1 down-regulates the expression of MTSS1 and promotes cell proliferation and migration, which may play an important biological role in the metastasis of TNBC.

Treatment strategy of mechanical hemolysis after mitral valve repair / 医学研究生学报

Objective　In recent yaers, mitral valve repair has been widely used in the surgical treatment of congenital and secondary mitral valve lesions. To investigate the mechanism and treatment strategy of mechanical hemolysis after mitral valve repair.　Methods　A total of 451 consecutive patients registrated in general hospital of southern theatre command who underwent mitral valve repair surgery between August 2010 and June 2018,of whom 16(3.5%) had complicated mechanical hemolysis(hemoglobinuria, jaundice, anemia), were retrospectively analyzed. Echocardiographic examination showed that there were 3 cases of mild mitral regurgitation(MR), 9 cases of moderate MR and 4 cases of severe MR, among which 75% of mitral regurgitation flow were rapid regurgitant jets (Vmax>4m/s). According to the treatment strategy,all cases were divided into two groups: the aggressive reoperation group（n=10）,patients received re-repair procedures within 1 week after hemolysis diagnosis. The conservative treatment group(n=6), patients received symptomatic treatment of hemodialysis, blood transfusion, diuresis, alkalization of urine, liver protection and oral metoprolol et al. All patients were followed up for 2 to 36 months, with an average (16±7.5) months, and the postoperative echocardiographic results, hemolysis symptom improvement and cardiac function were compared.　Results　No death occurred in the two groups after operation. The symptoms of patients in the aggressive reoperation group receded rapidly and discharged from hospital. 4 patients in the conservative treatment group received reoperation 3~11 weeks after surgery due to poor treatment effect (1 patient underwent re-repair and 3 patients underwent replacement), the other 2 patients received long-term conservative treatment. The cardiac function of the patients undergoing reoperation was maintained at level I~II. Echocardiographic examination showed that mild MR(n=10), mild~moderate MR(n=3), and no recurrence of mechanical hemolysis. Two patients with long-term conservative treatment, mild~moderate anemia, urinogen +~++, moderate MR, cardiac function at level II, were in a subclinical hemolytic state.　Conclusion　Mechanical hemolysis frequently occurs immediately or soon after mitral valve repair. Hemoglobinuria, jaundice, anemia and postoper echocardiography found the mitral regurgitant flow with high-shear stress, these helpful to the diagnosis. Surgery is an important factor affecting hemolysis. Hemolysis can be a sign of surgical failure, re-repair operation is the best treatment as soon as possible after the hemolysis has been diagnosed.Conservative treatment is not the priority choice.

Isolation and characterization of a novel strain (YH01) of Micropterus salmoides rhabdovirus and expression of its glycoprotein by the baculovirus expression system / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As one of the most important aquatic fish, Micropterus salmoides suffers lethal and epidemic disease caused by rhabdovirus at the juvenile stage. In this study, a new strain of M. salmoides rhabdovirus (MSRV) was isolated from Yuhang, Zhejiang Province, China, and named MSRV-YH01. The virus infected the grass carp ovary (GCO) cell line and displayed virion particles with atypical bullet shape, 300-500 nm in length and 100-200 nm in diameter under transmission electron microscopy. The complete genome sequence of this isolate was determined to include 11 526 nucleotides and to encode five classical structural proteins. The construction of the phylogenetic tree indicated that this new isolate is clustered into the Vesiculovirus genus and most closely related to the Siniperca chuatsi rhabdovirus. To explore the potential for a vaccine against MSRV, a glycoprotein (1-458 amino acid residues) of MSRV-YH01 was successfully amplified and cloned into the plasmid pFastBac1. The high-purity recombinant bacmid-glycoprotein was obtained from DH10Bac through screening and identification. Based on polymerase chain reaction (PCR), western blot, and immunofluorescence assay, recombinant virus, including the MSRV-YH01 glycoprotein gene, was produced by transfection of SF9 cells using the pFastBac1-gE2, and then repeatedly amplified to express the glycoprotein protein. We anticipate that this recombinant bacmid system could be used to challenge the silkworm and develop a corresponding oral vaccine for fish.

Recent advances in LncRNAs and chronic kidney disease / 药学学报

Long non-coding RNAs (LncRNAs), defined as transcripts which are hundreds of nucleotides with little or non-protein coding potential. Recently, LncRNAs have caught much more attentions, instead of considering as noises of genome transcripts, and indeed they have been found to play important roles associated with some biological processes, such as tumorigenesis, immunology dysfunction, metabolism adjustment, and so on. The incidence of chronic kidney disease (CKD) in different regions of the world is about 10% to 15%, with high growth rate and high unawareness, including the diabetic nephropathy, membranous nephropathy, etc. Previous publications also suggest that LncRNAs have a close relationship with the kidneys, and it may become new therapeutic targets or new biomarkers to diagnose diseases. In this review, we will summarize LncRNAs' functions with chronic kidney diseases, and discuss the prospects of the clinical applications of LncRNAs in the treatment of CKD treatment.

Surgical treatment of aorta coarctation / 医学研究生学报

Congenital coarctation of the aorta is a complex and common congenital heart disease, which can be combined with other heart defects. The clinical symptoms vary from the severity of the disease. In 1944, Crafoord successfully performed surgical repair of coarctation of the aorta, along with the progress of surgical Methods and the advent of interventional techniques, the treatment effect is improved, But no matter what kind of treatment it is, restenosis, aortic aneurysm, hypertension and other complications cannot be avoided. From long-term analysis of the followup Results , the overall effect of surgical treatment is still better than interventional treatment. This article reviews the surgical treatment of coarctation of the aorta.

Unilateral sinonasal disease in 376 adult patients: a retrospective study / 临床耳鼻咽喉头颈外科杂志

OBJECTIVES@#To investigate the clinical and pathological features of patients with unilateral sinonasal disease (USD).@*METHODS@#A retrospective analysis was completed on 376 adult patients with USD from January 2015 to December 2016. Their presenting symptoms, nasal endoscope, CT scanning, and pathology were analyzed respectively.@*RESULTS@#Among the 267 (71.01%) patients with inflammatory disease, there were 4 pathological types. And there were 8 pathological types in 60 (15.96%) patients with benign tumor. Of the 49 patients with malignant tumor, there were 15 pathological types which included squamous carcinoma, malignant melanoma, and lymphoma, as well as myoepithelial carcinoma and Mesodermal mesoderm. The onset age of inflammation group was younger than that of benign (<0.05) or malignant tumor groups (<0.05). The misdiagnosis rate was 8.33% in benign tumor (5/60), and 10.20% in malignant tumor (5/49). Nasal polyps was the most common misdiagnosis in the groups of benign and malignant tumor.@*CONCLUSIONS@#The pathology of adult patients with USD is complicated, and no specific clinical feature was found for distinguishing between benign and malignant lesions. The tumor took a quite proportion in adult patients with USD. Therefore, careful consideration should be taken before diagnosing patients with USD in order to reduce misdiagnosis rate.

Sedative Effect of Dexmedetomidine in Patients With Type Ⅰ Aortic Dissection After Total Arch Replacement Surgery / 中国循环杂志

Objectives: To evaluate the sedative effect of dexmedetomidine (DEX) in patients with type I aortic dissection (AD) after total arch replacement surgery. Methods: A total of 237 AD patients with arch involvement received total arch replacement were enrolled; there were 199 (84.0%) male and the patient's mean age was (48.79±12.65) years. Based on post-operative application of sedatives during ICU stay, the patients were divided into 2 groups: DEX group, patients received load dose DEX 1μg/kg by slow intravenous injection, then (0.2-0.7) μg/(kg·h ) by continuous infusion, n=126 and Midazolam (MDZ) group, patients received load dose MDZ 0.05μg/kg by slow intravenous injection, then (0.02-0.1) mg/(kg·h ) by continuous infusion, n=111. Same surgical method was used in both groups, the mechanical ventilation time, incidence of delirium and other relevant indexes were compared between 2 groups. Results: Compared with MDZ group, DEX group had reduced mechanical ventilation time (3.97±1.28) d vs (4.99±1.58) d and ICU stay time (6.63±1.71) vs (7.24±2.56) d, less incidences of delirium (8.7% vs 18.9%) and permanent dysneuria (5.65% vs 13.5%), all P<0.05. Conclusions: Compared with MDZ, DEX may effectively reduce mechanical ventilation time, ICU stay time and the incidence of dysneuria in type I AD patients after total arch replacement surgery; it had positive role for patient's recovery.

Synergistic induction of apoptosis by combination treatment of sinomenine with cisplatin in human fibrosarcoma HT-1080 cells / 中国病理生理杂志

AIM: To investigate the synergistic antitumor effect of sinomenine(SIN)and cisplatin(DDP) against human fibrosarcoma HT-1080 cells and its possible mechanism.METHODS:CCK-8 assay was used to detect the cytotoxic effect of SIN and DDP in HT-1080 cells,and the combination index(CI)of SIN and DDP was analyzed by Chou-Talalay method.The apoptosis was analyzed by flow cytometry.The protein levels of copper transporter 1(CTR1),gluta-thione S-transferase-π(GST-π),Bcl-2 and Bax were determined by Western blot.RESULTS: At 48 h after treatment with SIN or DDP at various concentrations,the cell viability was remarkably reduced(P<0.05), and the IC50values of DDP and SIN were 6.50 μmol/L and 1.06 mmol/L, respectively.When the inhibition rate of HT-1080 cells exceeded 25%, SIN in combination with DDP produced a synergistic effect(CI<1).Combination treatment of SIN with DDP signi-ficantly induced apoptosis of HT-1080 cells.SIN up-regulated the protein levels of CTR1 and Bax,and down-regulated the protein levels of GST-πand Bcl-2(P<0.05).CONCLUSION:SIN synergistic induces apoptosis with DDP in human fi-brosarcoma HT-1080 cells by up-regulating the protein levels of CTR1 and Bax, and down-regulating the protein levels of GST-πand Bcl-2.

Coarctation of the aorta with hypoplastic aortic arch :Analysis of midterm and longterm outcomes with autologous pulmonary patch aortoplasty / 医学研究生学报

Objective Previously we have reported the early and midterm benifit of autologous pulmonary patch in repairing aortic coarctation of hypoplastic aortic arch.This study aimed to assess its reliability and midterm and longterm outcomes.Methods We retrospectivly analyzed 42 pediatric patients with coarctation of the aorta (CoA) with hypoplastic aortic arch undergoing surgical repair with autologous pulmonary patch from May 2009 to May 2017 in General Hospital of Guangzhou Military Command of PLA.All the patients were allocated into either senior group (＞ 1 years) or junior group (≤1 years) according to the age of operation.The trans-coarctation gradient,pulmonary pressure and aortic Z value change were compared between two groups before and after the repair.Results There were 8 cases had early postoperative complications.However,no death had been reported during the postoperative time and the followed up period ranged from 4 months to 106 months (40.0± 15.5) months).The average pressure gradient of coarctation segment for all the patients was (11.9±6.4) mmHg,including 5 cases more than 25 mmHg.The pressure gradient and mean pulmonary arterial pressure after operation were significantly lower than those before operation (P＜0.05),The postoperative aortic arch Z value was greater than the preoperative value (P＜0.05).Compared with the preoperative period,the Z value of proximal transverse arch increased significantly(-0.64±0.44) vs (1.27±0.66),P＜0.05.Compared with junior group,the senior group had higher preoperative and postoperative pulmonary artery pressure (P＜0.05),and longer CPB time,aortic block time,ventilation time,ICU time and hospital stay time (P＜0.05).However,patients in the junior group had a higher pressure gradient through the aorta arch(P＜0.05) and a smaller Z value transverse arch aortic proximal and isthmus(P＜0.05) during the long-term period.The time of selective cerebral perfusion had no statistical difference between the two groups (P＞ 0.05).Conclusion Early surgery for coarctation of aorta with hypoplastic aortic arch,autologous pulmonary patch aortoplasty is a relatively ideal option with better midterm and longterm outcomes.

An 8-Week Low-Intensity Progressive Cycling Training Improves Motor Functions in Patients with Early-Stage Parkinson's Disease

BACKGROUND AND PURPOSE: The effects of high-intensity cycling as an adjuvant therapy for early-stage Parkinson's disease (PD) were highlighted recently. However, patients experience difficulties in maintaining these cycling training programs. The present study investigated the efficacy of cycling at a mild-to-moderate intensity in early-stage PD. METHODS: Thirteen PD patients were enrolled for 16 serial cycling sessions over a 2-month period. Motor function was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III) and Timed Up and Go (TUG) test as primary outcomes. The Montreal Cognitive Assessment (MoCA), modified Hoehn and Yahr Stage (mHYS), total UPDRS, Falls Efficacy Scale, New Freezing of Gait Questionnaire, Schwab and England Activities of Daily Living, 39-item Parkinson's Disease Questionnaire, Patient Global Impression of Change, and gait performance were assessed as secondary outcomes. RESULTS: The age and the age at onset were 59.67±7.24 and 53.23±10.26 years (mean±SD), respectively. The cycling cadence was 53.27±8.92 revolutions per minute. The UPDRS III score improved significantly after 8 training sessions (p=0.011) and 16 training sessions (T2) (p=0.001) in the off-state, and at T2 (p=0.004) in the on-state compared to pretraining (T0). The TUG duration was significantly shorter at T2 than at T0 (p < 0.05). The findings of MoCA, total UPDRS, double limb support time, and mHYS (in both the off- and on-states) also improved significantly at T2. CONCLUSIONS: Our pioneer study has demonstrated that a low-intensity progressive cycling exercise can improve motor function in PD, especially akinesia. The beneficial effects were similar to those of high-intensity rehabilitation programs.

Exploration of the teaching mode in critical clinical diagnosis and treatment / 基础医学与临床

Objective The clinical diagnosis and treatment remain unstandardized , and the teaching mode of critical clinical diagnosis and treatment in remote area was investigated and summarized .Methods The Critical Care County Working Group had summarized seven protocols of critical clinical diagnosis and treatment , which have been taught in the hospital located in the remote areas .The teaching mode included the theory , case discussions , and simulated practice .The examination was used to assess the effect of the teaching mode .Results A total of 573 ICU doctors from 15 provinces participated in the teaching courses .The accuracy rate of the examination was 49%at the baseline , then raised to 61%after the teaching course .Conclusions The critical diagnostic thinkings was poor in the remote area hospital ,and the education should be further strengthened .The teaching mode of "medical theory-case discussion-simulated practice" may improve the training of critical clinical diagnosis and treatment in the ICU doctors .