Protective effect and mechanism of AKAP1 on myocardial injury induced by highland hypobaric hypoxia / 中华劳动卫生职业病杂志

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

Association between muscle mass and quality of life in Shaanxi adults / 中华流行病学杂志

Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q1 group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q5 groups. Compared with the Q1 group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q2 group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study / 亚洲男科学杂志(英文版)

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Clinical application of targeted sealing with high viscosity bone cement and secondary injection of low viscosity bone cement in vertebroplasty / 中国骨伤

OBJECTIVE@#To observe the clinical efficacy of targeted sealing with high viscosity bone cement and secondary injection of low viscosity bone cement in the treatment of OVCFs patients with the fracture lines involved vertebral body margin.@*METHODS@#The elderly patients who underwent vertebroplasty for osteoporotic vertebral compression fractures from January 2019 to September 2021 were selected as the screening objects. Through relevant standards and further CT examination, 56 patients with fracture lines involving the anterior wall or upper and lower endplates of the vertebral body were selected for the study. There were 21 males and 35 females, aged from 67 to 89 years old with an average of (76.58±9.68) years. All 56 patients underwent secondary injection of bone cement during operation. Only a small amount of high viscosity cement was targeted to seal the edge of the vertebral body for the first time, and low viscosity cement was injected to the vertebral bodies during second bolus with well-distributed. The operation time, bone cement volume and bone cement leakage were recorded, and the pain relief was evaluated by visual analogue scale (VAS).@*RESULTS@#All patients were followed up for more than 3 months and the surgeries were successfully complete. The operation time was (50.41±10.30) min and the bone cement volume was (3.64±1.29) ml. The preoperative VAS was (7.21±2.41) points, which decreased significantly to (2.81±0.97) points 3 days after operation(P<0.05). Among the 56 patients, 2 cases(3.57%) had bone cement leakage, 1 case leaked to the paravertebral vein, and 1 case slightly bulged to the paravertebral through the crack when plugging the vertebral crack. Both patients had no obvious clinical symptoms.@*CONCLUSION@#In vertebroplasty surgery, targeted sealing of high viscosity bone cement and secondary injection of low viscosity bone cement can reduce intraoperative bone cement leakage and improve the safety of operation.

The progress of mechanical circulatory support devices / 中国胸心血管外科临床杂志

@#As a global disease, heart failure affects at least 26 million people, and its prevalence is still rising. Besides, the mortality rate and readmission rate remain high. Advanced heart failure is the terminal stage of various heart diseases, and often requires some treatments other than drug intervention, such as heart transplantation which is the gold standard for treatment of heart failure. However, limited by the number of donors, the number of heart transplants in the world has reached a bottleneck. There is a huge gap between the number of patients who need heart transplants and patients who get hearts for survival successfully in reality. With the exploration and development of mechanical circulation support devices for more than half a century, they have become a wonderful treatment for patients with advanced heart failure. This article will introduce the latest progress of mechanical circulatory support devices at home and abroad from the aspects of temporary and long-term devices.

Quality analysis of non-contrast-enhanced CT images synthesized from contrast-enhanced CT images by deep learning model / 中华放射医学与防护杂志

Objective:To synthesize non-contrast-enhanced CT images from enhanced CT images using deep learning method based on convolutional neural network, and to evaluate the similarity between synthesized non-contrast-enhanced CT images by deep learning(DL-SNCT) and plain CT images considered as gold standard subjectively and objectively, as well as to explore their potential clinical value.Methods:Thirty-four patients who underwent conventional plain scan and enhanced CT scan at the same time were enrolled. Using deep learning model, DL-SNCT images were generated from the enhanced CT images for each patient. With plain CT images as gold standard, the image quality of DL-SNCT images was evaluated subjectively. The evaluation indices included anatomical structure clarity, artifacts, noise level, image structure integrity and image deformation using a 4-point system). Paired t-test was used to compare the difference in CT values of different anatomical parts with different hemodynamics (aorta, kidney, liver parenchyma, gluteus maximus) and different liver diseases with distinct enhancement patterns (liver cancer, liver hemangioma, liver metastasis and liver cyst) between DL-SNCT images and plain CT images. Results:In subjective evaluation, the average scores of DL-SNCT images in artifact, noise, image structure integrity and image distortion were all 4 points, which were consistent with those of plain CT images ( P>0.05). However, the average score of anatomical clarity was slightly lower than that of plain CT images (3.59±0.70 vs. 4) with significant difference ( Z = -2.89, P<0.05). For different anatomical parts, the CT values of aorta and kidney in DL-SNCT images were significantly higher than those in plain CT images ( t=-12.89, -9.58, P<0.05). There was no statistical difference in the CT values of liver parenchyma and gluteus maximus between DL-SNCT images and plain CT images ( P>0.05). For liver lesions with different enhancement patterns, the CT values of liver cancer, liver hemangioma and liver metastasis in DL-SNCT images were significantly higher than those in plain CT images( t=-10.84, -3.42, -3.98, P<0.05). There was no statistical difference in the CT values of liver cysts between DL-SNCT iamges and plain CT images ( P>0.05). Conclusions:The DL-SNCT image quality as well as the CT values of some anatomical structures with simple enhancement patterns is comparable to those of plain CT images considered as gold-standard. For those anatomical structures with variable enhancement and those liver lesions with complex enhancement patterns, there is still vast space for DL-SNCT images to be improved before it can be readily used in clinical practice.

Diagnostic and therapeutic value of emergency gastroscopy for upper gastrointestinal bleeding combined with post percutaneous coronary intervention / 中华消化内镜杂志

From June 2015 to June 2020, 52 patients who underwent emergency gastroscopy and treatment for upper gastrointestinal bleeding after percutaneous coronary intervention (PCI) at the Renmin Hospital of Wuhan University were included and retrospectively analyzed. The etiologic diagnosis of bleeding, results of hemostatic treatment and occurrence of complications during the emergency gastroscopy were observed. Among the 52 patients, 47 cases (90.4%) were found to have lesions that could explain upper gastrointestinal bleeding under emergency gastroscopy, and the remaining 5 cases (9.6%) could not clearly diagnose the cause of bleeding. Twenty-six cases (50.0%) were treated with emergency endoscopic hemostasis, of which 25 cases (96.2%) were successful. The median time for emergency endoscopy was 18 min. Seven cases (13.5%) had transient slowing of heart rate and lowering of blood pressure without serious complications. This shows that emergency gastroscopy is safe and effective in the diagnosis and treatment of upper gastrointestinal bleeding combined with post-PCI.

Monochromatic images based on spectral CT for stent evaluation after transjugular intrahepatic portosystemic shunt / 中华放射学杂志

Objective:To investigate the optimal monochromatic level for evaluation of in-stent lumen after transjugular intrahepatic portosystemic shunt (TIPS) by dual-layer detector CT.Methods:Twenty-nine patients after TIPS were retrospectively enrolled who underwent abdomen enhanced examinations with portal venous phases by a dual-layer detector CT between December 2019 and July 2021. The mixed iterative image (conventional group) and monochromatic images (40 keV group, 50 keV group, 60 keV group and 70 keV group) were obtained by reconstruction. Circular regions of interest were placed in the in-stent of the cross-sectional reconstructed image and in the vertical spinal muscle on the same plane to obtain the corresponding average CT value and noise. The contrast to noise ratio (CNR) and signal to noise ratio (SNR) were calculated. Then 4-point scale was performed to evaluate image quality subjectively by 2 physicians blindly and separately. One-way ANOVA or Kruskal Wallis H rank-sum test was used for the overall analysis between groups, and LSD test or Dunn′s Bonforoni test was used for pairwise comparison within groups. Results:There was no significant difference in noise values among the 5 groups ( P>0.05). The difference of CNR and SNR between the 5 groups was statistically significant ( F=72.28, 56.45, P<0.001). The CNR and SNR in the 40 keV group were the highest, which were 50.4±15.7 and 59.3±18.4 respectively, and the difference was statistically significant ( P<0.001). Subjective scores showed statistically significant differences among the 5 groups (χ2=101.61, P<0.001). The score of the 40 keV group was higher than that of the 60 keV group, 70 keV group, and conventional group ( P<0.001), and there was no significant difference when compared with the subjective score of the 50 keV group ( P>0.05). Conclusions:The 40 keV monochromatic image of dual detector spectral CT is the best image to observe the lumen of the stent after TIPS.

Whole-genome sequencing and virulence characteristics of a community-acquired lower extremity emphysematous gangrene causing Klebsiella pneumoniae belonged to ST660 / 中华检验医学杂志

Objective:The whole-genome sequencing and virulence characteristics analysis of a Klebsiella pneumoniae isolate that caused lower limb gas gangrene were performed to provide a reference for the comprehensive understanding of molecular virulence characteristics of K. pneumoniae causing severe community-acquired infection. Methods:The patient was admitted to the emergency department for treatment on March 13, 2018.The main clinical symptoms of the patients were high fever, gas gangrene of the left lower limb, and diabetic ketoacidosis. The pus specimen was collected for the bacterial culture, isolates identification and antimicrobial susceptibility testing. Hypermucoviscous phenotype was detected by string test. The whole genome of the isolate was sequenced and the multi-site sequence typing, capsular serotyping, plasmid characteristics, virulence and antimicrobial resistance genes of the isolate were analyzed. Plasmid curing and conjugation experiments were used to analyze plasmid characteristics. The virulence of the strain was assessed by serum killing and Galleria mellonella lethality assays. A two-sample t-test was used to compare the differences in the lethal dose of 50% (LD 50) between the tested strains and reference strains against the G. mellonella larvae. Results:K. pneumoniae strain KPN41053 was identified, it was only resistant to ampicillin and was negative for hypermucoviscous phenotype. Whole genome sequencing showed that the length of KPN41053 chromosome was 5 377 071 bp, belonging to ST660 type, and the capsular type was K16. A IncFIB(K)/HI1B virulence plasmid (207 506 bp) with a sequence that was highly similar to pLVPK was harbored by KPN41053. The plasmid carried a variety of virulence genes, among which rmpA and rmpA2 were pseudogenes. The plasmid could not be transferred horizontally by conjugation. The variation strain KPN41053_PC was obtained by plasmid curing. Serum killing analysis showed that KPN41053 was serum resistant (Grade 6), and KPN41053_PC was serum intermediately sensitive (Grade 3). The lgLD 50 of KPN41053 had no difference with that of the hypervirulent control strain (ST23-K1 type) ( t=0.32, P=0.765), and was significantly lower than that of KPN41053_PC ( t=5.97, P=0.004). Conclusions:KPN41053 was an atypical hypervirulent K. pneumoniae that belonged to ST660 but without a hypermucoviscous phenotype. The virulence plasmid harbored by KPN41053 was its key virulence factor. Hypervirulent K. pneumoniae can lead to community-acquired gas gangrene in diabetic patient, which deserves clinical attention.

Value of multi-parameter MRI in the diagnosis of thyroid benign and malignant nodules / 中华放射学杂志

Objective:To explore the value of multi-parametric MRI for thyroid gland in differentiating benign and malignant thyroid nodules.Methods:From December 2018 to May 2020, 78 patients with 91 post-surgically pathologically confirmed thyroid nodules were enrolled in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. For each patient, the following MRI findings were obtained including the nodules′ location, size, shape, margin, signal intensity, cystic change, degree and pattern of contrast enhancement, involvement of surrounding structure, and ADC values. The time-intensity curve (TIC) were plotted and subtyped based on dynamic contrast enhancement MRI. The MRI findings between the benign and malignant thyroid nodules were compared using Mann-Whitney U test, χ 2 test or Fisher exact test. Multiple logistic regression analysis was used to select independent predictive variables and build a combined model, and the ROC curve was used to evaluate the diagnostic performance of each MRI finding and the combined model. Results:Between the benign and malignant thyroid nodules, the significant differences were found in size, shape, margin, presence of cystic changes, T 1WI signal intensity, ADC value, enhancement homogeneity, TIC subtypes and presence of thyroid capsule involvement ( P<0.05). Multivariate logistic analysis showed that ill-defined margin (OR=77.61), no presence of cystic changes (OR=36.11) and difference between TIC subtypes (OR=83.41) were independent predictive variables, and the area under the ROC curve (AUC) was 0.879, 0.788, and 0.751, respectively. The AUC, sensitivity and specificity of the combined model were 0.977, 0.986, and 0.904, respectively. Conclusions:Thyroid multi-parametric MRI derived findings can be used for the differential diagnosis of benign and malignant nodules. Combined with the independent risk factors with ill-defined margin, no presence of cystic changes, TIC of type plateau or washout, the diagnostic model has a higher diagnostic efficiency.

Active surveillance and molecular epidemiological study of intestinal colonization of carbapenem-resistant Enterobacterales / 中华传染病杂志

Objective:To investigate the detection rate of intestinal colonization of carbapenem-resistant Enterobacterales (CRE) in inpatients, and to analyze the molecular epidemiological characteristics of CRE strains.Methods:This was a prospective study. Stool, rectal swab or perianal swab specimens of 213 inpatients in the surgical intensive care unit (SICU), medical intensive care unit (MICU) and the department of hematology (transplantation ward) in The Second Hospital of Anhui Medical University were collected from March to December, 2019. MacConkey plate containing carbapenems was used to screen CRE strains, and bacteria identification and drug susceptibility test were conducted. Key strains were selected for whole genome sequencing (WGS). Besides, multilocus sequence typing, capsular serotype, drug resistance gene, virulence gene and plasmid carrying characteristics of these strains were analyzed. Using KPN FJ723042 sequence as a reference, the single-nucleotide polymorphism (SNP) of all strains was analyzed.Results:Twenty-three CRE strains were detected, with a detection rate of 10.8%(23/213), which included 15(65.2%) carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, three (13.0%) Escherichia coli strains, three (13.0%) Enterobacter cloacae strains and two (8.7%) Citrobacter freundii strains. SNP cluster analysis showed that the 15 CRKP strains had two main clonotypes, which were both predominant in SICU. Fifteen strains of CRKP were type ST11-K64. All these strains carried β-lactamase Klebsiella pneumoniae carbapenemase 2 ( blaKPC-2 ), and 12 strains carried regulator of mucoid phenotype gene A2 ( rmpA2) and iucABCD. Conclusions:The detection rate of intestinal colonization of CRE in inpatients is high, and most strains are CRKP of type ST11-K64. These CRKP strains have both multidrug resistance and virulence characteristics, which are risks for hospital transmission.

Effect of estrogen-related receptor α on lipopolysaccharide-induced vascular endothelial apoptosis and tight junction protein degradation / 中华急诊医学杂志

Objective:To explore the effect of estrogen-related receptor α (ERRα) on lipopolysaccharide (LPS)-induced vascular endothelial cell apoptosis and tight junction protein degradation.Methods:RPMVECs transfected with shERRα were cultured in vitro and divided into four groups: Normal control group (Ctr group); shERRα knockdown group (shERRα group); normal cells + LPS treated group (LPS group): The cells in the six-well plates were cultured in serum-free medium for 12 h, and then treated with 20 μg/mL LPS for 12 h; and shERRα+LPS group: ERRα knockdown cells were treated as the LPS group. ROS fluorescence kit was used to detect the intracellular ROS levels . Apoptosis ratio was detected by TUNEL staining, AnnexinV-FITC and PI. Cell membrane ZO-1 expression was detected by cellular immunofluorescence, and the levels of apoptosis-related proteins Bcl-2, Bax, Smac, Cytochrome c, and tight junction protein ZO-1, as well as the expression of Occludin, JAM-A and E-Ca at molecular level were detected by Western blot.Results:Compared with the Ctr group and the shERRα group, the ROS level, apoptosis rate (TUNEL test: 16.44 ± 2.55; and flow cytometry test: 23.56 ± 2.22), the expression of pro-apoptotic proteins Bax, Smac and Cytochrome c were increased in the LPS group, while the expression of anti-apoptotic proteins Bcl-2 and tight junction protein were decreased. In the LPS group. Cellular immunofluorescence results showed that the ZO-1 was degraded in the cell membrane and the network structure was broken. Compared with the LPS group, inhibition of ERRα in the shERRα+LPS group increased cell damage.Conclusions:ERRα can negatively regulate the apoptosis and affect the function of pulmonary microvascular endothelial cells, thereby regulating sepsis-induced acute lung injury.

Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice / 中国中药杂志

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

Value of arterial spin label technique in 3.0 T MR scanner on evaluating blood flow of thyroid glands in healthy adults / 中华放射学杂志

Objective:To investigate the feasibility and reproducibility of using three-dimensional arterial spin labeling (3D-ASL) technique to evaluate the thyroid blood flow (TBF) in healthy adults and compare the difference in TBF between subjects with different gender and age.Methods:In this prospective study, 100 healthy adult subjects were enrolled from November 2018 to June 2019 in Chinese Academy of Medical Sciences Cancer Hospital, Shenzhen Hospital. All subjects received thyroid 3D-ASL MRI scanning, but several subjects were excluded from analysis for reasons including intolerance to examination ( n=1), overt artifacts ( n=11), abnormality detected in thyroid gland during conventional MRI ( n=15), resulting in 73 subjects included. Two attending radiologists independently evaluated the quality of ASL images and measured the TBF in upper, middle and lower poles of each lobe in thyroid gland bilaterally. Cohen’s Kappa was used to test the agreement in image quality between 2 radiologists, while intraclass correlation (ICC) analysis was implemented to evaluate the consistency in TBF measurements. Univariate variance analysis was used to compare the TBF in upper, middle and lower pole of thyroid gland unilaterally, and student t-test was performed to test the difference in TBF between two lobes, or in the same lobe but between different gender or age groups. Results:For image quality, 2 radiologists have good agreement (Kappa=0.753, P<0.001). In terms of TBF, consistency was moderate in the lower pole of left lobe between 2 radiologists (ICC=0.648, P<0.001), but good in the remaining parts of thyroid gland (all ICC>0.75, P<0.001). Unilaterally, TBF in the middle pole was significantly higher than those in the upper or lower pole ( P<0.001), but no significant difference was found between the upper and lower pole ( P>0.05). Regardless of upper, middle or lower pole, TBF in the right lobe was higher than the counterpart in the left lobe ( t=6.182, 6.294, 4.896, P<0.001). Between male subjects ( n=31) and female subjects ( n=42), no significant difference was found in the corresponding upper, middle or lower pole of thyroid lobe unilaterally ( P>0.05). As for age group, TBF in the middle pole of thyroid gland was higher in the middle age group (45-59 years old, n=12) than that in the young adult group (18-44 years old, n=61) ( t=3.868, P=0.003 for the left lobe, and t=2.647, P=0.022 for the right lobe), but no significant difference was found in the upper or lower pole of the unilateral thyroid lobe ( P>0.05). Conclusion:ASL can accurately measure blood flow perfusion in the thyroid gland with good reproducibility.

Common errors analysis on measuring the APPLS related future liver remnant with CT′s image post-processing software / 中华普通外科杂志

Objective:To explore whether CT image post-processing software can accurately measure (associating liver partition and portal vein ligation for staged hepatectomy, ALPPS) related (future liver remnant, FLR).Methods:Clinical data of 9 liver cancer patients undergoing ALPPS were retrospectively analyzed in the Second Affiliated Hospital of Air Force Military Medical University from Mar 2015 to May 2019. All cases were divided into 2 groups by measurement: CT′s image post-processing software, or Myrian software. Two groups were compared with each other by paired t-test. Results:FLR from group CT′s image post-processing software was larger than that by Myrian software, there was statistical difference ( t=2.512, P=0.019). The mistakes of FLR measurements by the radiologist using CT′s image post-processing software couldbe caused by: (1)Lacking theoretical knowledge of liver surgery; (2) Adding devitalized tissue of hepatic section into future liver remnant; (3) Concept confusion about liver anatomy; (4) Lack of precision measurement. Conclusions:The inaccuracies generated during the ALPPS related future liver remnant measurements in CT′s image post-processing technique are all caused by human factors. These problems could be solved if the radiologist who operates 3D reconstruction receives liver surgery training or works with liver surgeons.

Mechanism of crocin compounds from Gardenia jasminoides in Zhejiang Province by network pharmacology / 中草药

Objective: To investigate the pharmacological mechanism of the crocin compounds from Gardenia jasminoides in Zhejiang Province by using network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of G. jasminoides from Zhejiang. Methods: Our previous research results showed that the Zhejiang area of Gardenia crocin content and other areas have significant difference. Based on the results, the crocin compounds from G. jasminoides were used to predict the targets according to Pubchem, Uniprot, STITCH, SWISS, and TCMSP online databases. Cytoscape software was used to construct compound-target-disease network of the G. jasminoides crocin ingredients. The targets were analyzed by Gene ontology (GO) enrichment and KEGG pathway analysis using CTD online analysis platform to analyze main biological pathways for obtaining the deep mechanism of G. jasminoides in Zhejiang. Results: The crocin compounds from G. jasminoides in Zhejiang Province were obtained through previous work and network pharmacology screening, such as crocin-1 and crocin-2, and 18 corresponding targets were acted, such as FGF2, VEGFA, KDR, and FLT1. These targets could joint in pathways, such as GPCR, Rap1, and Ras signaling pathway. These ingredients are mainly used to treat 18 related diseases such as cardiovascular diseases, tumors and digestive system. Conclusion: The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, signaling pathway and disease network of traditional Chinese medicine (TCM), and provide useful information and data support for giving a further study on TCM resources in different regions of China.

Effect of auranofin combined with antineoplastic vorinostat on bactericidal activities against gramnegative bacteria and study on the target of auranofin / 中华传染病杂志

Objective To find the target of auranofin with the antibacterial activity against gramnegative bacteria and to investigate the effect of the combination of auranofin and vorinostat on the antibacterial activity against gram-negative bacteria.Methods The strains of E.coli lacking thioredoxin reductase (TrxR)was used to find the target gene.The potential synergies of the combination of auranofin and vorinostat for E.coli strain,A.baumannii strain,P.aeruginosa strain,K.pneumonia strain and muhidrug-resistant (MDR)A.baumannii strain were evaluated using susceptibility tests,micro-dilution checkerboard tests and time-kill studies.The genes related to Trx (trxA,trxB,trxC) and the gene expressed glutathione (gor) of E.coli BW25113 strains (WT) were separately knocked out to observe the effect of auranofin on minimum inhibitory concentration (MIC) and the time-kill kinetics of △trxC and △gor.Furthermore,the complemented strains (C-trxA,C-trxB,C-trxC,C-gor) were used to verify and define the genetic targets.Results According to the results of susceptibility tests,MICs of auranofin were 64 mg/L for E.coli strain BW25113 and K.pneumonia strain ATCC 43816,128 mg/L for P.aeruginosa strain PA14 and 32 mg/L for both A.baumannii strain ATCC 17978 and A.baumannii strain AB5075.However,MICs of vorinostat are 512 mg/L for all isolates.The fractional inhibitory concentration indexes (FICIs) of the combination of auranofin and vorinostat for E.coli strain BW25113,A.baumannii strain ATCC 17978,MDR A.baumannii strain AB5075,K.pneumonia starin ATCC 43816 and P.aeruginosa strain PAl4 were 0.313,0.375,0.375,0.375,and 0.375,respectively,with all values ＜ 0.5,which showed synergy.In susceptibility tests of knockout strains,MICs of auranofin for △trxC increased from 64 mg/L to 256 mg/L,decreased to 16 mg/L for △gor,and no changes for △trxA and △trxB.Auranofin showed the same antibacterial activities against the complemented strains (C-trxC,C-gor) and E.col BW25113,which decreased by about 1.8 lg colong formins units (CFU)/mL of bacterial counts.However,the antibacterial activity of auranofin was significantly reduced for △trxC,and decreased by ＜ 1 lg CFU/mL of bacterial counts.For Agor,bacterial counts decreased 4.6 lg CFU/mL,and the antibacterial activity markedly increased.Conclusions The potential target gene of auranofin against gram-negative bacteria could be trxC,which provides new ideas and methods for the clinical treatment of multidrug-resistant gram-negative bacteria.

Application of three-dimensional CT and image classification in percutaneous vertebraplasty for osteoporotic vertebral compression fractures / 中国骨伤

OBJECTIVE@#To explore the application of three-dimensional CT and image classification in the treatment of osteoporotic vertebral compression fracture(OVCFs) by percutaneous vertebroplasty(PVP).@*METHODS@#A total of 90 patients with OVCFs who were treated with PVP in Linqu People's Hospital of Shandong Province from April 2016 to March 2018 were selected as subjects. There were 31 males and 59 females, aged from 63 to 84 years old. Bone mineral density measurements were performed in all patients to confirm the presence of osteoporosis and imaging examinations were performed to confirm the presence of vertebral fractures. The fracture area was determined by MRI fat surpressed image before operation and three-dimensional modeling was performed to calculate the volume of fracture area. Three dimensional CT imaging of bone cement in fracture area was performed after PVP and the volume ratio of bone cement in fracture area was calculated by computer aided design software, by which patients were divided into groups for study. Forty-one patients whose volume ratio of bone cement in fracture area less than 50% are control group and the rest of 90 patients are observation group. Visual analogue scale (VAS) and Oswestry Disability Index(ODI) were collected in two groups before operation and 1 day, 3 months after operation. The amount of bone cement was recorded after operation.@*RESULTS@#All operations were successful. There were 3 cases of cement leakage in control group and 4 cases in observation group. All patients had no obvious clinical symptoms. After continuous observation and follow-up for 3 months, no complications such as adjacent vertebral fracture, infection, bone cement displacement were found. There was no significant difference in bone cement doses and bone cement leakage between two groups(>0.05). There was no significant difference in preoperative VAS and ODI between two groups(>0.05). All VAS and ODI obviously decreased(<0.05) at 1 day after operation and in observation group the decrease was more significant (<0.05). At 3 months after operation there was no significant difference between two groups. This may have been due to basically healing of vertebral fractures at 3 months after surgery and the pain was no longer significantly related.@*CONCLUSIONS@#PVP can significantly improve clinical symptoms of OVCFs and bone cement filling in fracture area is the key to the short-term effect of PVP.

Real-time dynamic recording of cerebral cortical vascular embolization and regeneration in rats / 生理学报

The purpose of this study was to establish a method to record the dynamic process of vascular regeneration and remodeling in rat cerebral ischemic regions. An animal brain window model was established to continuously observe the changes of rat cortical vascular ischemia in vivo, and the model of cerebral ischemia was established by photochemical embolization. Optical coherence tomography (OCT) was performed to record the formation of vascular blockage and the injury and regeneration of small vessels during cerebral ischemia recovery. The results showed that 30 min of laser irradiation could completely block the cortical vessels in rats. Within 24-48 h after ischemia, the degree of brain injury was the greatest, and the number of blood vessels in the ischemic region reached the minimum. Then the blocked blood vessels began to be dredged, and the small blood vessels around the ischemic area began to regenerate. Small blood vessels in the superficial/deep layers of the cortex disappeared significantly after laser irradiation. During 10 d after ischemia, the blocked blood vessels were gradually dredged and recovered. On the 10th day after laser irradiation, a large number of neovascularization appeared in the superficial layer of cortex, but the deep vessels did not recover. These results indicate that the method established in this study can observe the changes of blood vessel in cerebral ischemic region continuously, which lays a foundation for further quantitative study on the dynamics of embolized blood vessels and peripheral capillaries during the recovery of cerebral ischemia.

Effect of particulate matter 2.5 at urban centre of Hangzhou on lung impairment in rats / 中国应用生理学杂志

OBJECTIVE@#To explore the effect of ambient particle matter 2.5 (PM2.5) collected in the urban center of Hangzhou on the lung injury of rats and on the activating of endoplasmic reticulum pathway.@*METHODS@#PM2.5 samples were collected on quartz fiber filters using a PM2.5 high-volume air sampler in the urban area of Hangzhou. The collected PM2.5 particles were extracted in ultrapure water and concentrated by vacuum freeze-drying. Twenty-four male Sprague-Dawly (SD) rats were randomly divided into 3 groups:saline control group, low dose PM2.5 exposure group (5 mg/kg BW) and high dose PM2.5 exposure groups (25 mg/kg BW). Each group received intratracheal instillation of PM2.5, once a week for 4 weeks. Twenty-four hours after the last exposure, the rats were narcotized and sacrificed, left lung was isolated and fixed with 4% paraformaldehyde for histopathological detection. The bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total antioxidant capacity (T-AOC) level, the activities of superoxide dismutase (SOD) and lactic dehydrogenase (LDH) in BALF were detected by chemical colorimetry. The level of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) cytokines in BALF was measured by enzyme linked immunosorbent assay (ELISA). And the protein expressions of glucose-regulated protein 78 (GRP78), phosphorylated protein kinase receptor-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor (p-eIF2α), transcription factors C/EBP homologue protein (CHOP), inositol-requiring enzyme 1α (IRE1α) and X-box binding protein 1 (XBP1) in lung tissue were determined by Western blotting.@*RESULTS@#Compared with control group, rats in both low dose (5 mg/kg) and high dose (25 mg/kg) PM2.5-treated groups showed obviously dose-dependent pulmonary toxicity including thickening of alveolar walls, narrowing of alveolar space, interstitial hyperplasia and inflammatory cell infiltration. Compared with control group, T-AOC level and the SOD activity in BALF in both PM2.5-treated groups were decreased dose-dependently (<0.05), whereas the LDH activity in BALF were increased in a dose-dependent manner (<0.05). Exposure to PM2.5 resulted in a increasing of the release of proinflammatory cytokines including TNF-α, IL-1β and IL-6 in rat lung in a dose-dependent manner (<0.05). The levels of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α and spliced XBP1 (XBP1-S) were significantly up-regulated, whereas the level of unspliced XBP1 (XBP1-U) was down-regulated in the rat lung tissue of high-dose PM2.5 treated group.@*CONCLUSIONS@#The PM2.5 in the urban area of Hangzhou can significantly cause lung inflammatory injury in rats. Both oxidative stress and activation of ER stress pathways may be related to such PM2.5 inhalation-induced lung inflammatory injury.