Andrographolide loaded montmorillonite attenuated enterotoxigenic Escherichia coli induced intestinal barrier injury and inflammation in a mouse model.

Montmorillonite (MMT), a natural absorbent agent, has widely been accepted for its antidiarrhea function in human and farm animals; however, its specific physicochemical property limits its biological function in practical use. In the current study, raw MMT was loaded by andrographolide, namely andrographolide loaded montmorillonite (AGP-MMT). The microstructure of AGP-MMT was observed by scanning electron microscope (SEM) and X-ray diffraction (XRD). The effect of AGP-MMT on the growth performance, intestinal barrier and inflammation was investigated in an enterotoxigenic Escherichia coli (ETEC) challenged mice model. The results show that the microstructure of MMT was obviously changed after andrographolide modification: AGP-MMT exhibited a large number of spheroid particles, and floccule aggregates, but lower interplanar spacing compared with MMT. ETEC infection induced body weight losses and intestinal barrier function injury, as indicated by a lower villus height and ratio of villus height/crypt depth, whereas the serum levels of diamine oxidase (DAO), D-xylose and ETEC shedding were higher in the ETEC group compared with the CON group. Mice pretreated with AGP-MMT showed alleviated body weight losses and the intestinal barrier function injury induced by ETEC challenge. The villus height and the ratio of villus height/crypt depth, were higher in mice pretreated with AGP-MMT than those pretreated with equal levels of MMT. Pretreatment with AGP-MMT also alleviated the increased concentration of serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), and the corresponding genes in the jejunum induced by ETEC infection in mice. The protein and mRNA levels of IL-1ß were lower in mice pretreated with AGP-MMT than those with equal levels of MMT. The results indicate that AGP-MMT was more effective in alleviating intestinal barrier injury and inflammation in mice with ETEC challenge than MMT.

[The effect of chronic endometritis on the clinical outcomes of patients with failure of first embryo transfer].

Objective: To investigate the effect of chronic endometritis (CE) on the clinical outcomes of patients with failure of first embryo transfer. Methods: A total of 5 605 cycles of frozen-thawed single blastocyst transfer in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to June 2021 were retrospectively collected. After the failure of first embryo transfer, all patients underwent hysteroscopy, and when necessary, endometrial pathology and immunohistochemistry were combined to diagnose CE. Patients were divided into two groups: non-CE group (5 033 cycles) and CE treatment group (572 cycles). The main outcome was live birth rate and the secondary outcomes included clinical pregnancy rate and early abortion rate. The quantitative data were represented by Median (Q1, Q3). The rank sum test was used for comparison between groups. The factors related to live birth rate were analyzed by binary logistic regression model. Results: The incidence of CE was 10.21% (572 cycles) in patients with the failure of first embryo transfer. The maternal age in the non-CE group was 31.0 (29.0, 34.0) years old, and that in the CE treatment group was 31.0 (29.0, 34.0) years old (P<0.001). There was a statistically significant difference in endometrial preparation between the two groups (P=0.010). The endometrial thickness in the CE group was 9.0 (8.2, 10.3) mm on progesterone transformation day, which was higher than that of [9.5 (8.6, 11.0) mm] in the non-CE group (P<0.001). There was no significant difference in clinical pregnancy rate (60.3% (3 035 cycles) vs 63.1% (361 cycles), P=0.193), early abortion rate (17.1% (520 cycles) vs 20.5% (74 cycles), P=0.112) and live birth rate (49.2% (2 477 cycles) vs 49.3% (282 cycles), P=0.969) between the non-CE group and the CE treatment group. The maternal age, endometrial thickness on progesterone transformation day and blastocyst grade were related factors of the live birth rate, and the OR(95%CI) were 0.94 (0.93-0.96), 1.10 (1.06-1.14) and 2.07 (1.84-2.32)), respectively (all P<0.001). Compared with the non-CE group, the CE treatment group did not affect the live birth rate after transplantation, the aOR (95%CI) was 0.99 (0.82-1.18), P=0.882. Conclusions: For patients who underwent the failure of first embryo transfer, hysteroscopy is recommended before single frozen blastocyst transfer, and if necessary, combined with immunohistochemical screening for CE. After standardized treatment, CE patients could obtain similar clinical pregnancy rate, early miscarriage rate and live birth rate as non-CE patients.

[Outcome of surgical repair for aortic coarctation with coexisting descending aortic aneurysm in adult patients].

Objective: To evaluate the efficacy of surgical treatment of aortic coarctation combined with descending aortic aneurysm in adult patients. Methods: This is a retrospective cohort study. Adult patients with aortic coarctation who were hospitalized in Beijing Anzhen Hospital from January 2015 to April 2019 were enrolled. The aortic coarctation was diagnosed by aortic CT angiography, and the included patients were divided into the combined descending aortic aneurysm group and the uncomplicated descending aortic aneurysm group based on descending aortic diameter. General clinical data and surgery-related data were collected from the included patients, and death and complications were recorded at 30 days after surgery, and upper limb systolic blood pressure was measured in all patients at discharge. Patients were followed up after discharge by outpatient visit or telephone call for their survival and the occurrence of repeat interventions and adverse events, which included death, cerebrovascular events, transient ischemic attack, myocardial infarction, hypertension, postoperative restenosis, and other cardiovascular-related interventions. Results: A total of 107 patients with aortic coarctation aged (34.1±15.2) years were included, and 68 (63.6%) were males. There were 16 cases in the combined descending aortic aneurysm group and 91 cases in the uncomplicated descending aortic aneurysm group. In the combined descending aortic aneurysm group, 6 cases (6/16) underwent artificial vessel bypass, 4 cases (4/16) underwent thoracic aortic artificial vessel replacement, 4 cases (4/16) underwent aortic arch replacement+elephant trunk procedure, and 2 cases (2/16) underwent thoracic endovascular aneurysm repair. There was no statistically significant difference between the two groups in the choice of surgical approach (all P>0.05). In the combined descending aortic aneurysm group at 30 days after surgery, one case underwent re-thoracotomy surgery, one case developed incomplete paraplegia of the lower extremity, and one case died; and the differences in the incidence of endpoint events at 30 days after surgery were similar between the two groups (P>0.05). Systolic blood pressure in the upper extremity at discharge was significantly lower in both groups compared with the preoperative period (in the combined descending aortic aneurysm group: (127.3±16.3) mmHg vs. (140.9±16.3) mmHg, P=0.030, 1 mmHg=0.133 kPa; in the uncomplicated descending aortic aneurysm group: (120.7±13.2) mmHg vs. (151.8±26.3) mmHg, P=0.001). The follow-up time was 3.5 (3.1, 4.4) years. There were no new deaths in the combined descending aortic aneurysm group, no transient ischemic attack, myocardial infarction or re-thoracotomy surgery, and one patient (1/15) suffered cerebral infarction and 10 patients (10/15) were diagnosed with hypertension. The differences in the occurrence of endpoint events during postoperative follow-up were similar between the two groups (P>0.05). Conclusion: In experienced centers, long-term prognosis of patients with aortic coarctation combined with descending aortic aneurysm is satisfactory post surgical intervention.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

[The clinical effect and imaging features of accordion maneuver in promoting bone healing at the docking site after tibial transport under ultrasonic monitoring].

Objective: To explore the imaging features and clinical effect of accordion maneuver in promoting the bone healing at the docking site after tibial transport under ultrasonic monitoring. Methods: Retrospective analysis was conducted on the clinical data of 16 patients with tibial bone transport who were admitted to the Department of Orthopedics, the second Hospital of Shanxi Medical University from May 2018 to October 2019. All the patients were treated with accordion maneuver to promote bone healing at the docking site under ultrasound monitoring. There were 14 males and 2 females, aged (45.3±14.3) years (range: 6 to 61 years). Before tibial bone transport, the length of the tibial defect of 16 patients was (6.0±2.6) cm (range: 2.0 to 12.1 cm). The operation steps of accordion maneuver were as follows: pressurization for 2 weeks, suspension for 12 days, distraction for 2 weeks, retraction for 2 weeks, and then stop the operation to consolidate the bone mineralization. During accordion treatment, ultrasound was used to monitor the size of hematoma, Adler grade of blood flow signal and the changes of new callus in and around the docking site. X-ray was performed to monitor bone healing at the docking site. Pearson correlation coefficient was used to analyze the correlation between the size of hematoma, the resistance index of blood flow signal and the bone healing time of the docking site. Paley healing criterion was used to evaluate the bone healing and functional recovery of the patients. Results: During accordion maneuver, ultrasound examination showed that the Adler grade of blood flow signals around the docking site increased gradually before retraction and then decreased gradually, but the degree of callus mineralization continued to increase gradually. After 2 weeks of pressure on the docking site, hematoma was observed in 14 patients by ultrasound examination. X-ray showed that all docking sites had bony healing, with the healing time of (30.8±4.9) weeks (range: 23 to 40 weeks).The size of the hematoma was negatively correlated with the healing time of the docking site (r=-0.819,P<0.01). No hematoma was found in 2 patients, and after continuous observation for 20 weeks, there was still no obvious callus connection at the docking site. After bone cortical removal, ultrasound examination showed hematoma formed at the docking site. Accordion maneuver was continued, and the docking site healed at 30 and 32 weeks after surgery, respectively. There was a negative linear correlation between hematoma size at 2 weeks of compression and the blood flow resistance index at 2 weeks of retraction in 16 patients (r=-0.801, P<0.01). The patients were followed-up for (14.5±3.2) months (range: 10.6 to 20.2 months). At the last follow-up, 12 patients were evaluated as excellent and 4 were evaluated as good by Paley healing criteria. Conclusion: The distraction and compression stress applied in accordion maneuver can promote bone healing at the docking site, and ultrasound can monitor early signs of bone healing at the docking site to help determine the tendency of bone healing.

[Metabolomics study of urine with Benzene, Toluene and Xylene combined exposure based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Objective: To study the effects of combined occupational exposure of benzene, toluene, and xylene on human metabolism at an overall level, and to screen biomarkers related to the combined occupational exposure of benzene, toluene, and xylene, and to explore the mechanism of early health effects preliminarily caused by combined occupational exposure of benzene, toluene, and xylene by identification of biomarkers and retrieval of metabolic pathways. Methods: A shoe-making company was selected as the research site. Twenty subjects for the exposed group and the control group were selected separately, and urine of the subjects was collected. The metabolic profiles of the samples were collected by liquid chromatography time-of-flight mass spectrometry, and professional metabolomics and multivariate statistical analysis software were used to establish PCA and OPLS-DA analysis models to screen potential biomarkers and identify biomarkers. Finally, based on the dynamic changes and trends of potential biomarkers between groups, the mechanism of body damage caused by benzene, toluene, and xylene was initially explored. Results: Urine metabolomics analysis showed that the metabolic profile of urine samples of the benzene, toluene, and xylene combined exposure group was different from that of the control group. 27 potential biomarkers that were closely related to the combined exposure of benzene, toluene, and xylene were screened and identified. These potential biomarkers were enriched in 16 metabolic pathways, of which 3 pathways were significantly enriched (P<0.05) , respectively, lysine metabolism, amino sugar metabolism, and nucleotide sugar metabolism. Conclusion: The metabonomics method can well reflect the changes in the metabolome of urine samples in the occupational population after the combined exposure of benzene, toluene, and xylene, which will help us better evaluate the risk of combined exposure of benzene, toluene, and xylene and prevent and control their health risks.

[Acute kidney injury diagnosed by elevated serum creatinine increases mortality in ICU patients following non-cardiac surgery].

Objective: To analyze whether acute kidney injury (AKI) patients diagnosed by elevated serum creatinine had a higher risk of in-hospital mortality following non-cardiac surgery compared with those diagnosed by oliguria alone according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods: This was a secondary analysis of a previous retrospective cohort study. A total of 729 consecutive adult patients with high risk of AKI admitted to the intensive care unit (ICU) of Peking University First Hospital after non-cardiac surgery were enrolled in the previous study from July 2017 to June 2018. Postoperative AKI patients were diagnosed and categorized according to KDIGO criteria. In this secondary analysis, all patients with AKI were selected. Patients diagnosed by elevated serum creatinine were enrolled into the AKI-Scr group, while those with oliguria alone were included in the AKI-UO group. A multivariable logistic regression model was established to assess the relationship between elevated serum creatinine and in-hospital mortality in AKI patients. Results: Of 188 AKI patients [(71±14) years, 114 males (60.6%)], 72 (38.3%) and 116 (61.7%) patients were enrolled in AKI-Scr and AKI-UO group, respectively. The rate of in-hospital mortality was 16.7% in AKI-Scr group, which was significantly higher than that in AKI-UO group (0.9%, P<0.001). Furthermore, patients in AKI-Scr group had longer postoperative hospital and ICU stay, more duration of mechanical ventilation and higher total medical costs (all P<0.05). Multivariate logistic regression analysis revealed that AKI-Scr (OR=20.286, 95%CI: 2.544-161.797, P=0.004) and preoperative hypoproteinemia (OR=4.897, 95%CI: 1.240-19.329, P=0.023) were independent risk factors for in-hospital mortality in postoperative AKI patients. Conclusions: AKI patients diagnosed by increased serum creatinine had a higher risk of in-hospital mortality following non-cardiac surgery, accompanied by several worsen short-term outcomes and higher total medical costs, compared with those diagnosed by oliguria alone according to the KDIGO criteria. More attention should be paid to AKI patients diagnosed by elevated serum creatinine, to improve the prognosis.

Experimental study on synergistic effect of HIFU treatment of tumors using Bifidobacterium bound with cationic phase-change nanoparticles.

OBJECTIVE: Anaerobic bacteria can enter the solid tumor in the hypoxic region to colonize and proliferate. Aggregation of nanoparticles in the tumor area can enhance molecular imaging and therapy. It is hypothesized that the combination of the two could possibly achieve better imaging and tumor treatment. This study presents a biocompatible bacteria-based system that can deliver cationic phase-change nanoparticles (CPNs) into solid tumor to achieve enhanced imaging and treatment integration. MATERIALS AND METHODS: Cationic phase-change nanoparticles (CPNs) and Bifidobacterium longum (BF) were mixed to determine the best binding rate and were placed in an agar phantom for ultrasonography. BF-CPNs complex adhesion to breast cancer cells was observed by laser confocal microscopy. In vivo, BF-CPNs and control groups were injected into tumors in breast cancer nude mouse models. Nanoparticles distribution was observed by ultrasound and in vivo fluorescence imaging. HIFU ablation was performed after injection. Gross and histological changes were compared and synergy was evaluated. RESULTS: Bifidobacterium longum (BF) and CPNs were combined by electrostatic adsorption. The BF-CPNs particles could increase the deposition of energy after liquid-gas phase-change during High Intensity Focused Ultrasound (HIFU) irradiation of tumor. CONCLUSIONS: This study shows a valid method in diagnosis and therapy integration for providing stronger imaging, longer retention time, and more effective tumor treatment.

One-day protocol for 18F-FDG and 13N-ammonia PET/CT with uptake decoupling score in differentiating untreated low-grade glioma from inflammation. / Protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con escala de desacoplamiento de la captación para diferenciar el glioma de bajo grado no tratado de la inflamación.

PURPOSE: Accurate identification of low-grade gliomas (LGGs; World Health Organization grades I and II) and their differentiation from brain inflammation lesions (BILs) remains difficult; however, it is essential for treatment. This study assessed whether a one-day protocol for voxel-wise 18F-FDG and 13N-ammonia PET/CT with uptake decoupling analysis could differentiate LGGs from BILs. MATERIALS AND METHODS: Twenty-eight patients with LGGs and 16 patients with BILs underwent 18F-FDG and 13N-ammonia PET/CT on the same day before any type of therapy. The decoupling score and tumor-to-normal tissue (T/N) ratio of 18F-FDG and 13N-ammonia were calculated at each location. Student's t-test was used to compare values, and ROC curve analysis was used to establish a cut-off value for the T/N ratio and decoupling score. Area under the curve (AUC) was calculated to evaluate differential efficacy. RESULTS: Significant differences were observed in 13N-ammonia T/N ratio (p=0.018) and decoupling score (p=0.003) between LGGs and BILs; however, the 18F-FDG T/N ratio did not show any differences (p=0.413). Optimal cut-off values for 18F-FDG T/N ratio, 13N-ammonia T/N ratio, and decoupling score were 0.73, 0.97, and 2.31, respectively, with corresponding AUCs of 0.48, 0.68, and 0.77. The respective sensitivity, specificity, and accuracy parameters using these cut-off values were 53.6%, 62.5%, and 56.8%, respectively, for 18F-FDG; 50.0%, 75.0%, and 59.1%, respectively, for 13N-ammonia; and 60.7%, 93.8%, and 72.7%, respectively, for decoupling score. CONCLUSIONS: 18F-FDG/13N-ammonia uptake decoupling score can be used to discriminate between LGGs and BILs. Use of a decoupling map of these two tracers can improve visual analysis and diagnostic accuracy.

[Determination of seven urinary metabolites of benzene, toluene and xylene by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry].

Objective: To develop a method using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to determine the urinary metabolites of benzene, toluene and xylene. The selected metabolites are S-phenylmercapturic acid (S-PMA) , trans, trans-muconic acid (t, t-MA) , 8-hydroxy-2 deoxyguanosine (8-OHdG) , hippuric acid (HA) , 2-methylhippuric acid (2-MHA) , 3-methylhippuric acid (3-MHA) and 4-methylhippuric acid (4-MHA) . Methods: The urine sample was pretreated using methanol to precipitate the proteins. HSS T3 chromatographic column was used to separate the metabolites. The mass spectrometric acquisition was carried out using multiple reaction monitoring (MRM) after ionization with ESI source. External standard method was used for quantification. Results: All the standard curves showed good linear relation, and r of the seven metabolites was all above 0.999. The detection limits and quantitative limits of the seven metabolites were 0.01-500 ng/ml and 0.02-1 000 ng/ml (based on the actual dilution ratio) , respectively. The average spiked recoveries of four loadings ranged from 85.8% to 109.9%. The intra-day and inter-day precisions were 0.2%-4.5% and 0.6%-9.5%, respectively. The samples can be kept for at least 14 days at both 4 ℃ and -20 ℃. Conclusion: This method is simple, rapid and highly sensitive with low cost, and its accuracy, precision and stability can meet the daily test requirements. It can be applied for the determination of urinary S-PMA, t, t-MA, 8-OHdG, HA, 2-MHA, 3-MHA and 4-MHA for the occupational population exposed to benzene, toluene and xylene.

Retraction Note: Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

This article has been retracted at the request of the authors. After publication, the authors found that in Figure 2B-a the first two images in the third row partly overlapped and that there is also overlap between the fourth and fifth image in the second row. The two images were taken from two adjacent wells, treated by ZA 0.3uM-CM or ZA 0.75uM-CM, with or without PL 1.25uM. This overlap may have been caused by mishandling in the imaging process when the authors made microscope observations and so the findings are no longer reliable. All authors agree to this retraction.

Research on correlations of magnetic resonance imaging features and pathological changes in liver cancer with Beclin1 expression.

OBJECTIVE: Our study aims to explore the correlations of magnetic resonance imaging (MRI) features and pathological changes in liver cancer with the messenger ribonucleic acid (mRNA) and protein expression of Beclin1. PATIENTS AND METHODS: The mRNA and protein expression levels of Beclin1 in 42 cases of liver cancer and para-carcinoma tissues from liver cancer patients were detected via fluorescence quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry, and its correlations with the clinicopathological characteristics and MRI features were analyzed. RESULTS: The mRNA expression of Beclin1 in liver cancer tissues was significantly higher than that in para-carcinoma tissues, and statistical correlation between pathological grade and mass size of liver cancer was found (p < 0.05). The immunohistochemical results revealed that the Beclin1 positive expression was mainly located in the cytoplasm, and the level was significantly increased compared with that in corresponding para-carcinoma tissues (p < 0.05). The MRI showed that both Min-apparent diffusion coefficient (ADC) and Mean-ADC in Beclin1 high-expression group were significantly lower than those in Beclin1 low-expression group. CONCLUSIONS: The Beclin1 expression plays an important role in the occurrence and development of liver cancer. MRI shows significant correlation with the level of Beclin1 in liver cancer, which provides certain value in the evaluation of the biological behaviors and prognosis of liver cancer.

[The application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional areas].

Objective: This study aimed to analyze the application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional area, and to illustrate the minimal safe threshold by ROC method. Methods: Fifty-seven patients with gliomas in the functional areas were enrolled in the study at Beijing Tiantan Hospital from 2015 to 2017. Anesthesia was maintained intravenously with propofol 10% and remifentanil. Throughout the resection process, cortical or subcortical stimulation threshold was determined along tumor border using monopolar or bipolar electrodes. The motor pathway was identified and protected from resection according to the stimulation threshold and transcranial MEPs. Minimal threshold in each case was recorded. Results: Total resection was achieved in 32 cases(56.1%), sub-total resection in 22 cases(38.6%), and partial resection in 3 cases(5.3%). Pre-operative motor disability was found in 9 cases. Compared with pre-operative motor scores, 19 exhibited impaired motor functions on day 1 after surgery, 5 had quick recovery by day 7 after surgery, and 7 had late recovery by 3 months after surgery. At 3 months, 7 still had impaired motor function. The frequency of intraoperative seizure was 1.8%(1/57). No other side effect was found during electronic monitoring in the operation. The ROC curve revealed that the minimal safe monopolar subcortical threshold was 5.70 mA for strength deterioration on day 1 and day 7 after surgery. Univariate analysis revealed that decreased transcranial MEPs and minimal subcortical threshold ≤5.7 mA were correlated with postoperative strength deterioration. Conclusions: Cortical and subcortical stimulation threshold has its merit in identifying the motor pathway and guiding the resection for tumors within the functional areas. 5.7 mA can be used as the minimal safe threshold to protect the motor pathway from injury.

[Perioperational management of gynecological cancer patients with severe internal medical complications: a serial of 37 clinical cases].

Objective: To evaluate the effectiveness and safety of perioperational management of gynecological cancer patients with severe internal medical complications. Methods: We collected 37 cases of gynecological cancer patients with severe internal medical complications who were hospitalized in Peking University First Hospital from Jan. 2010 to Nov. 2014. All of the cases were planned to move to ICU right after operation based on the preoperational assessment of anesthetist and physician. The median age was 69.4 years, and 25 cases (68%,25/37) of them were over 70 years old. The pathological types, preoperational complications, preoperational preparation, process of anesthesia and surgery, post-operational short-term morbidity were retrospectively analyzed. Results: (1) Pathological type: among 37 cases of gynecological cancer patients, 16 cases of endometrial cancer, 12 cases of ovarian cancer, 5 cases of vulvar cancer, 3 cases of uterine sarcoma and 1 case of fallopian cancer. (2) Preoperational complication: all the patients had more than 2 types of internal complications, 34 cases (92%, 34/37)of them had no less than 3 types of internal complications. The preoperational complications mainly included 25 cases of hypertension, 13 cases of coronary heart disease and 5 cases of arrhythmia, 5 cases of history of cerebral infarction or hemorrhage, 19 cases of diabetes and 1 case of obesity, 6 cases of allergic asthma and history of pulmonary embolism. (3) Preoperational preparation: medication were taken according to internal physicians to make blood pressure lower than 140/90 mmHg(1 mmHg=0.133 kPa), fasting blood glucose lower than 8.0 mmol/L, postprandial blood glucose lower than 10.0 mmol/L and cardiac function return to a generally normal status. (4) Process of anesthesia and surgery: 37 cases completed operation successfully after preoperational anesthetic assessment and internal medication. No perioperational death was observed. (5) Post-operational morbidity: 17 cases of post-operational short-term morbidity were observed before discharge, including 9 cases of poor wound healing, 5 cases of gastro-intestinal dysfunction and 3 cases of pulmonary infection. All of them were improved or cured. Conclusion: Surgery is safe and applicable to gynecological cancer patients with severe internal medical complications on the compressive management of anesthesia assessment, perioperational internal adjustment and post-operational multi-discipline treatment.

[A prediction model for severe postoperative hypoxemia after surgery for Standford type A aortic dissection].

OBJECTIVE: To study the risk factors of severe postoperative hypoxemia after surgery for Standford type A aortic dissection and establish a prediction model. METHODS: Data of 411 consecutive patients from January 2014 to April 2015, who underwent surgery for Standford type A aortic dissection in the department of cardiovascular surgery of Beijing Anzhen Hospital, were retrospectively analyzed. All the cases were divided into two groups according to the appearance of severe postoperative hypoxemia. All the data about potential risk factors was put into the database and analyzed by logistic regression. The prediction model was then established upon acquired independent risk factors. Discrimination and calibration of the prediction model were assessed with ROC curve and Hosmer and Lemeshow goodness of fit test. RESULTS: The perioperative in-hospital mortality was 6.57%(27/411). Severe postoperative hypoxemia (PaO2/FiO2≤100 mmHg) happened in 69 cases within 48 hours after procedures, with an incidence rate of 17.1%. The logistic regression demonstrated that body mass index (BMI), age, preoperative serum myoglobin, preoperative serum creatinine, preoperative serumalanine aminotransferase, the time of cardiopulmonary bypass, re-exploration within 48 hours after procedures were the independent risk factors for severe postoperative hypoxemia. The prediction model was then established based on these independent risk factors. The area under ROC curve of the model was 0.785, and the P value in Hosmer and Lemeshow goodness of fit test was 0.625. CONCLUSION: The logsitic model built in this study succeeded to predict the incidence of severe postoperative hypoxemia after surgery for Standford type A aortic dissection, and it could meet the doctors' requirement with its excellent discrimination and calibration.

Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk).

Intranasal atomised dexmedetomidine optimises surgical field visualisation with decreased blood loss during endoscopic sinus surgery: a randomized study.

BACKGROUND: Safe and effective endoscopic sinus surgery (ESS) depends on distinct surgical visibility. Various interventions are proposed to reduce intranasal bleeding. This study investigated whether intranasal atomised dexmedetomidine (DEX) provided optimal surgical conditions and decreased blood loss. METHODS: ASA I or II patients undergoing ESS were randomly assigned to receive either 2 µg/kg intranasal DEX (group D) or the same volume of saline (group N) 15 min before induction. Lund-Mackay (LM) scores represented the extent of the preoperative surgical lesion and were obtained based on the computed tomographic scans. Estimated blood loss was recorded. The visibility of the surgical field was rated by surgeons on a numerical rating scale (NRS) or assessed using Boezaart score. RESULTS: Median blood loss in groups D and N was 75 and 100 ml, respectively. NRS and Boezaart score for surgical condition were lower in group D than in group N. LM score showed a positive correlation between NRS and Boezaart score in group N but not in group D. CONCLUSION: Intranasal atomised DEX resulted in improved surgical conditions with less bleeding during ESS despite the severity of the preoperative surgical lesion.

Characterization of the male-specific lethal 3 gene in the oriental river prawn, Macrobrachium nipponense.

In this study, male-specific lethal 3 homolog (Mnmsl3) was cloned and characterized from the freshwater prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) by rapid amplification of cDNA ends. The deduced amino acid sequences of Mnmsl3 showed high-sequence homology to the insect Msl3 and contained a conserved chromatin organization modifier domain and an MORF4-related gene domain. Real-time quantitative reverse transcription-polymerase chain reaction showed that the Mnmsl3 gene was expressed in all the investigated tissues, with the highest level of expression in the testis. The expression level of Mnmsl3 between males and females was different in the gonad (testis or ovary), abdominal ganglion, and heart. The results revealed that the Mnmsl3 gene might play roles in regulating chromatin and in dosage compensation of M. nipponense. Real-time quantitative reverse transcription-polymerase chain reaction also revealed that Mnmsl3 mRNA expression was significantly increased in both 5 and 20 days post-larvae after metamorphosis, suggesting that Mnmsl3 plays complex and important roles in the early embryonic development and sex differentiation of M. nipponense.

MMP13 is a critical target gene during the progression of osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a degenerative joint disease affecting a large population of people. The mechanism of this highly prevalent disease is not fully understood. Currently there is no effective disease-modifying treatment for OA. The purpose of this study was two-fold: 1) to investigate the role of MMP13 in the development of OA; and 2) to evaluate the efficacy of the MMP13 inhibitor CL82198 as a pharmacologic treatment for preventing OA progression. METHODS: To investigate the role of the endogenous Mmp13 gene in OA development, tamoxifen was administered to two-week-old Col2CreER;Mmp13fx/fx (Mmp13Col2ER) and Cre-negative control mice for five days. OA was induced by meniscal-ligamentous injury (MLI) when the mice were 10 weeks old and MLI or sham-operated joints were harvested 4, 8, 12, or 16 weeks after surgery. To evaluate the efficacy of CL82198, MLI surgery was performed on 10-week-old wild type mice. CL82198 or saline was administered to the mice daily beginning immediately after the surgery for up to 16 weeks. The joint tissues collected from both experiments were evaluated by cartilage grading, histology/histomorphometry, immunohistochemistry (IHC), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The ability of CL82198 to inhibit MMP13 activity in vitro was confirmed by ELISA. RESULTS: The OA progression was decelerated in Mmp13Col2ER mice 8, 12, and 16 weeks post-surgery. Cartilage grading by blinded observers confirmed decreased articular cartilage degeneration in Mmp13Col2ER mice at 8, 12 and 16 weeks compared to Cre-negative mice. Histomorphometric analysis demonstrated that Mmp13Col2ER mice had a higher articular cartilage area and thickness at 12 and 16 weeks post-surgery compared to the control mice. Results of IHC revealed greater type II collagen and proteoglycan expression in Mmp13Col2ER mice. Chondrocyte apoptosis, as determined by TUNEL staining, was higher in control mice compared to Mmp13Col2ER mice. CL82198 inhibited MMP13 activity in conditioned media from vehicle (>85%) or bone morphogenetic protein 2 (BMP2)-treated (>90%) primary murine sternal chondrocytes. Intraperitoneal injection of CL82198 decelerated MLI-induced OA progression, increased type II collagen and proteoglycan levels, and inhibited chondrocyte apoptosis compared to saline treatment as determined by OA grading, histology, histomorphometry, IHC, and TUNEL staining, respectively. CONCLUSIONS: Mmp13 is critical for OA progression and pharmacologic inhibition of MMP13 is an effective strategy to decelerate articular cartilage loss in a murine model of injury-induced knee OA.