BL-918, a small-molecule activator of ULK1, induces cytoprotective autophagy for amyotrophic lateral sclerosis therapy.

Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS. Autophagic signaling is initiated by unc-51 like autophagy activating kinase 1 (ULK1) complex. We previously identified that BL-918 as a specific ULK1 activator, which exerted cytoprotective effect against Parkinson's disease in vitro and in vivo. In this study we investigated whether BL-918 exerted a therapeutic effect against ALS, and characterized its pharmacokinetic profile in rats. In hSODG93A-NSC34 cells, treatment with BL-918 (5, 10 µM) dose-dependently induced ULK1-dependent autophagy, and eliminated toxic SOD1 aggregates. In SODG93A mice, administration of BL-918 (40, 80 mg/kg, b.i.d., i.g.) dose-dependently prolonged lifespan and improved the motor function, and enhanced the clearance of SOD1 aggregates in spinal cord and cerebral cortex through inducing autophagy. In the pharmacokinetic study conducted in rats, we found BL-918 and its 2 metabolites (M8 and M10) present in spinal cord and brain; after intragastric and intravenous administration, BL-918 reached the highest blood concentration compared to M8 and M10. Collectively, ULK1 activator BL-918 displays a therapeutic potential on ALS through inducing cytoprotective autophagy. This study provides a further clue for autophagic dysfunction in ALS pathogenesis.

The Effects of Placental Mesenchymal Stem Cells Labeled With Ultrasmall Superparamagnetic Iron Oxides on the Growth of Colorectal Cancer Cells.

OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, with effective intervention and treatment being essential for CRC management. This study investigated the effects of human placental mesenchymal stem cells (PMSCs) labeled with ultrasmall superparamagnetic iron oxides (USPIOs) on the growth of CRC cells and the feasibility of 3.0-T magnetic resonance (MR) imaging as an in vivo tracer. METHODS: Twenty subcutaneous CRC HT-29 xenograft model in immunodeficient mice was established. Mice injected with labeled PMSCs were considered as the experimental group. Thereafter, the growth and MR signal changes of xenograft tumors of every nude mouse were measured. Then, growth curve was plotted, and the MR image quality in different sequences was analyzed. Pathological staining was performed after MR scan. RESULTS: Ultrasmall superparamagnetic iron oxides-labeled PMSCs had no significant influence on biological characteristics ( P > 0.05). The growth of tumors in mice in the experimental group before the injection of PMSCs was similar to that of the control group. Contrarily, the tumor growth rate in the experimental group on day 5 post-PMSCs injection was slightly lower than that of the control group. Moreover, the tumor volume on day 14 was noticeably smaller than in the control group. The tracing ability of T2* mapping sequences for USPIOs-labeled cells was significantly more effective than T2-weighted image and T2 mapping sequences. CONCLUSIONS: Ultrasmall superparamagnetic iron oxides-labeled PMSCs injected into CRC transplanted tumors can be studied for a long period of time. Furthermore, 3.0-T MRI in vivo molecular imaging was demonstrated to be effective for CRC intervention.

Autophagy-dependent removal of α-synuclein: a novel mechanism of GM1 ganglioside neuroprotection against Parkinson's disease.

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases. In this study, we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson's disease (PD) in vivo and in vitro. Mice were injected with MPTP (30 mg·kg-1·d-1, i.p.) for 5 days, resulting in a subacute model of PD. PD mice were treated with GM1 ganglioside (25, 50 mg·kg-1·d-1, i.p.) for 2 weeks. We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues. In the MPP+-treated SH-SY5Y cells and α-synuclein (α-Syn) A53T-overexpressing PC12 (PC12α-Syn A53T) cells, treatment with GM1 ganglioside (40 µM) significantly decreased α-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress. We further revealed that treatment with GM1 ganglioside promoted autophagy, evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins (LC3-II and p62) in the MPP+-treated SH-SY5Y cells. Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside. Using GM1 ganglioside labeled with FITC fluorescent, we observed apparent colocalization of GM1-FITC and α-Syn as well as GM1-FITC and LC3 in PC12α-Syn A53T cells. GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12α-Syn A53T cells and the MPP+-treated SH-SY5Y cells, which was inhibited by 3-MA. Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance.

Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.

[Development of a Forensic Multiplex Amplification STR Kit for 15 Autosomal STR Loci and 10 Y-STR Loci].

OBJECTIVE: To establish a multiplex STR genotyping method for autosomal STR and Y-STR loci in forensic biological practice. METHODS: Widely used autosomal STR loci and Y-STR loci were selected. A set of PCR primers was designed, and a 5-dye fluorescent labeled STR multiplex PCR reagent kit was developed. RESULTS: A kit was developed which can simultaneously detect 15 autosomal STR loci, 10 Y-STR loci, and an Amelogenin. CONCLUSION: The 15 autosomal STR plus 10 Y-STR kit in combination with capillary electrophoresis method was used to STR genotyping with accurate and reliable results. The new one-step testing kit can potentially be widely used in forensic cases and DNA databank in the future.

Construction and identification of the adenoviral vector with dual reporter gene for multimodality molecular imaging.

In this study, the recombinant adenovirus (Ad) vector containing dual reporter gene [i.e. human transferrin receptor gene (TFRC) and firefly luciferase reporter gene] was constructed to provide a novel experimental tool for magnetic resonance (MR) and bioluminescence dual-modality molecular imaging. The cDNA of TFRC was amplified by polymerase chain reaction (PCR) and cloned into the multiple cloning site of pShuttle-CMV-CMV-Luciferase vector. After identification by Sfi I digestion and sequencing, pShuttle-TFRC-Luciferase vector and the adenoviral backbone vector (pAdeno) were subjected to homologous recombination. The correct recombinant plasmid was then transfected into 293 packaging cells to produce adenoviral particles and confirmed by PCR. After infection of human colorectal cancer LOVO cells with Ad-TFRC-Luciferase, the expressions of transferrin receptor (TfR) and luciferase protein were detected respectively by Western blotting and bioluminescence imaging in vitro. The results showed that TFRC gene was successfully inserted into the adenoviral shuttle vector carrying luciferase gene. DNA sequence analysis indicated that the TFRC gene sequence in the shuttle plasmid was exactly the same as that reported in GenBank. The recombinant plasmid was identified correct by restriction digestion. Ad-TFRC-Luciferase recombinant adenovirus was constructed successfully, and the virus titer was 1.6×10(10) pfu/mL. Forty-eight h after dual reporter gene transfection, the expressions of TfR and luciferase protein were increased significantly (P<0.01). It was concluded that the recombinant adenovirus vector with dual reporter gene was successfully established, which may be used for in vivo tracing target cells in multimodality imaging.

Shared Decision-Making in Hemophilic Arthropathy Rehabilitation: A Qualitative Study.

Purpose: To probe into the needs and barriers underlying patients' participation in shared decision-making related to rehabilitation nursing for hemophilic arthropathy. Patients and Methods: The phenomenological research approach was adopted to conduct a series of semi-structured, in-depth interviews with 15 patients with hemophilic arthropathy undergoing rehabilitative treatments, 10 caregivers, and 7 healthcare providers from a hemophilia treatment center in Shanxi province, China. Colaizzi's seven-step method of data analysis was applied to organize, analyze, and extract the themes from the interview materials. Results: Three main themes emerged from the analysis: the status quo of the healthcare system (insufficient decision support systems and mismatch between healthcare providers' and patients' resources), circumstances of provider-patient interactions (lack of information exchange and unbalanced power structure between healthcare providers and patients), and patient-related factors influencing participation in decision-making (lack of self-efficacy, personal characteristics, family and social decision support, and attitude toward participation in decision-making). Conclusion: Participation in rehabilitation decision-making among patients with hemophilic arthropathy is affected by multiple barriers. Healthcare professionals should improve their understanding of shared decision-making, offer patients active guidance on participating in the decision-making process, prioritize their affective needs, and formulate professional and effective solutions to support shared decision-making as early as possible.

[Current status and trend of acupuncture-moxibustion for myofascial pain syndrome: a visual analysis of knowledge graph based on CiteSpace and VOSviewer].

Bibliometric and scientific knowledge graph methods were used to analyze the research status and hot spots of acupuncture-moxibustion in treatment of myofascial pain syndrome (MPS) and explore its development trend. The articles of both Chinese and English versions relevant to MPS treated by acupuncture-moxibustion were searched in CNKI, VIP, Wanfang, SinoMed and WOS from the database inception to March 20, 2023. Using Excel2016, CiteSpace6.2.R2 and VOSviewer1.6.18, the visual analysis was conducted by means of the cooperative network, keyword co-occurrence, keyword timeline, keyword emergence, etc. From Chinese databases and WOS database, 910 Chinese articles and 300 English articles were included, respectively. The annual publication volume showed an overall rising trend. Literature output of English articles was concentrated in Spain, China, and the United States, of which, there was less cross-regional cooperation. In the keyword analysis, regarding acupuncture-moxibustion therapy, Chinese articles focused on "acupuncture", "electroacupuncture" and "acupotomy"; while, "dry needling" and "injection" were dominated for English one. Clinical study was the current hot spot in Chinese databases, in comparison, the randomized controlled double-blind clinical trial was predominant in WOS. Both Chinese and English articles were limited in the report of mechanism research. The cooperation among research teams should be strengthened to conduct comparative research, dose-effect research and effect mechanism research with different methods of acupuncture-moxibustion involved so that the evidences can be provided for deeper exploration.

Acinous cell AR42J-derived exosome miR125b-5p promotes acute pancreatitis exacerbation by inhibiting M2 macrophage polarization via PI3K/AKT signaling pathway.

BACKGROUND: The incidence rate of acute pancreatitis (AP), which is a pathophysiological process with complex etiology, is increasing globally. miR-125b-5p, a bidirectional regulatory miRNA, is speculated to exhibit anti-tumor activity. However, exosome-derived miR-125b-5p in AP has not been reported. AIM: To elucidate the molecular mechanism of exosome-derived miR-125b-5p promoting AP exacerbation from the perspective of the interaction between immune cells and acinar cells. METHODS: Exosomes derived from AR42J cells were isolated and extracted in active and inactive states by an exosome extraction kit, and were verified via transmission electron microscopy, nanoparticle tracking analysis, and western blotting. RNA sequencing assay technology was used to screen differentially expressed miRNAs in active and inactive AR42J cell lines, and bioinformatics analysis was used to predict downstream target genes of miR-125b-5p. The expression level of miR-125b-5p and insulin-like growth factor 2 (IGF2) in the activated AR42J cell line and AP pancreatic tissue were detected by quantitative real-time polymerase chain reaction and western blots. The changes in the pancreatic inflammatory response in a rat AP model were detected by histopathological methods. Western Blot was used to detect the expression of IGF2, PI3K/AKT signaling pathway proteins, and apoptosis and necrosis related proteins. RESULTS: miR-125b-5p expression was upregulated in the activated AR42J cell line and AP pancreatic tissue, while that of IGF2 was downregulated. In vitro experiments confirmed that miR-125b-5p could promote the death of activated AR42J cells by inducing cell cycle arrest and apoptosis. In addition, miR-125b-5p was found to act on macrophages to promote M1 type polarization and inhibit M2 type polarization, resulting in a massive release of inflammatory factors and reactive oxygen species accumulation. Further research found that miR-125b-5p could inhibit the expression of IGF2 in the PI3K/AKT signaling pathway. Additionally, in vivo experiments revealed that miR-125b-5p can promote the progression of AP in a rat model. CONCLUSION: miR-125b-5p acts on IGF2 in the PI3K/AKT signaling pathway and promotes M1 type polarization and inhibits M2 type polarization of macrophage by inhibiting IGF2 expression, resulting in a large release of pro-inflammatory factors and an inflammatory cascade amplification effect, thus aggravating AP.

[Anatomic distribution of embolus at CT pulmonary angiography in patients suspected acute pulmonary embolism].

OBJECTIVE: To summarize and analyse the morphology and distribution of embolus in patients suspected acute pulmonary embolism. METHODS: The CT pulmonary angiography (CTPA) imagings of 279 patients suspected acute pulmonary embolism were analysed retrospectively in Ningxia from January 2004 through June 2006 and in Beijing from September 2005 through October 2006. The incidence of central embolus, peripheral embolus and mixed embolus, and the distribution and the morphology of embolus in different levels of pulmonary arteries were analysed. RESULTS: A total of 279 patients (158 males, 121 females; Median age was 63 years) were recruited. The incidence of central embolus, peripheral embolus and mixed embolus were 3.5%, 40.9% and 55.6%, respectively. There were 1850 emboli found above the segmental pulmonary arterial, 58.2% were found in right pulmonary artery, and 41.8% in left pulmonary artery. For all of the emboli, there were 29.7% in bilateral upper lobes, 18.3% in medial lobe and lingual lobe, and 49.8% in bilateral lower lobes. The percent of A, B and C type embolus were 81.7%, 7.6% and 10.7%, respectively. CONCLUSION: It was not unusual for the peripheral thrombosis, and can be improved to detect peripheral thrombosis by thin-slice CT scan. The distribution of embolus in pulmonary vascular and the distribution of blood flow was consistent, the number of embolus in right lung were more than left lung, and lower lobes more than upper lobes and middle lobes.

[Coronary artery disease diagnosis with 64-slice spiral CT coronary artery angiography in China and abroad: a meta analysis].

OBJECTIVE: This meta-analysis evaluated the accuracy of diagnosing coronary artery disease using 64-section spiral computed tomography, and compared the difference between Chinese studies and abroad studies. METHODS: Relevant English and Chinese articles published from 1998 to 2009 were searched in Cochrane library, Medline, Embase database, OVID database and CNKI. Heterogeneity was tested, pooled weighted sensitivity and specificity and the corresponding 95%CI were calculated. Summary receiver operating characteristic (SROC) curve was drawn and the area under the curve was calculated, differences between studies from China and abroad were compared. RESULTS: A total of 433 articles were searched and 108 articles were included (46 English articles and 62 Chinese articles) after excluding articles of research purposes or design does not match. Because of no gold standard, no blind, can not be calculated literature data, 7 and 20 (P > 0.05), 44 and 6 (P < 0.05), 3 and 1 (P < 0.05) Chinese studies and English articles respectively were excluded. Twenty-seven articles fulfilled all inclusion criteria (8 Chinese and 19 foreign studies) In 8 Chinese studies the pooled weighted sensitivity and specificity and area under SROC curve was 0.892 (95%CI: 0.868 - 0.913), 0.972 (95%CI: 0.966 - 0.977) and 0.983 (95%CI: 0.966 - 1.000) at segment-based analysis. In 19 foreign studies, the pooled weighted sensitivity and specificity and area under SROC curve was 0.971(95%CI: 0.957 - 0.982), 0.878 (95%CI: 0.852 - 0.902) and 0.973 (95%CI: 0.958 - 0.989) at patient-based analysis, 0.917 (95%CI: 0.895 - 0.936), 0.919 (95%CI: 0.909 - 0.928) and 0.974 (95%CI: 0.964 - 0.984) at vessel-based analysis, 0.882 (95%CI: 0.868 - 0.895), 0.959 (95%CI: 0.956 - 0.962) and 0.985 (95%CI: 0.978 - 0.992) at segment-based analysis. Pooled weighted pecificity of 64-section spiral CT angiography at segment-based analysis has significant different between home and abroad (P < 0.05). CONCLUSIONS: Meta-analysis showed that noninvasive 64-section spiral computed tomography could correctly diagnose coronary artery disease with high sensitivity and specificity. Quality of related studies performed in abroad is significantly higher than those performed in China.

[Predicting value of various clinical probability scores for diagnosis of lower limb deep venous thrombosis in Chinese patients].

OBJECTIVE: To evaluate the predicting value of Wells, Kahn, St. André and Constans scores for the diagnosis of deep venous thrombosis in Chinese patients. METHODS: A total of 274 patients suspected with deep venous thrombosis was prospectively blinded evaluated with the four clinical-score systems. Sensitivity, specificity, positive predictive value, negative predictive value and receiver operation curves were calculated for four clinical scores according sonography results. RESULTS: Sonography evidenced deep venous thrombosis in 88 out of 274 patients. The sensitivity, specificity, positive predictive value and negative predictive value was 77.3%, 65.6%, 51.5% and 85.9%, respectively, for Wells score; 58%, 55.9%, 38.3% and 73.8%, respectively, for Kahn score; 64.8%, 55.4%, 40.7% and 76.9%, respectively, for St. André score and 86.4%, 37.6%, 39.6% and 85.4%, respectively, for Constans score. ROC was 0.761 for Wells score, which was similar as that of Constans score (0.759), then followed by St. André score (0.627) and Kahn score (0.591). CONCLUSION: Our results showed that Wells score and Constans score are superior to Kahn score or St. André score for diagnosing patients with suspected deep venous thrombosis in terms of sensitivity, negative prediction value and ROC values.

[Radial growth of dominant coniferous species and their responses to climate changes in the Altay Mountains, China]. / é˜¿å°”æ³°å±±ä¸»è¦é’ˆå¶æ ‘ç§æ ‘æœ¨å¾„å‘ç”Ÿé•¿åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Based on the standard method of dendrochronology, we examined the tree-ring width index of two dominant tree species in the Altay Mountains, China, including Picea obovata and Larix sibirica. We analyzed the basal area increments (BAI) of those two species and the relationships between their radial growth and the climatic factors, which were compared in similar habitats. The results showed that the BAI of P. obovata was greater than L. sibirica, but the radial growth rate of L. sibirica was greater. In recent 60 years, the radial growth of P. obovata negatively correlated with high temperature in the fast growing stage of previous year, while the high temperature in June of current year promoted the radial growth of L. sibirica. There was a significantly negative correlation between radial growth of L. sibirica with temperature in January of current year. The sensitivity of tree growth to climate showed an obvious increase after an abrupt climate change under the background of recent warming and wetting trend in mid-1980s. Results of the moving correlation analysis showed that the response of the radial growth of P. obovata and L. sibirica to temperature and precipitation were enhanced under the background of climate change in the study area.

Comparison of safety, efficacy, and long-term follow-up between "one-step" and "step-up" approaches for infected pancreatic necrosis.

BACKGROUND: Although the "Step-up" strategy is the primary surgical treatment for infected pancreatic necrosis, it is not suitable for all such patients. The "One-step" strategy represents a novel treatment, but the safety, efficacy, and long-term follow-up have not yet been compared between these two approaches. AIM: To compare the safety, efficacy, and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment. METHODS: This was a retrospective analysis of infectious pancreatic necrosis patients who underwent "One-step" or "Step-up" necrosectomy at Xuan Wu Hospital, Capital Medical University, from May 2014 to December 2020. The primary outcome was the composite endpoint of severe complications or death. Patients were followed up every 6 mo after discharge until death or June 30, 2021. Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0, and statistical significance was set at P < 0.05. RESULTS: One-hundred-and-fifty-eight patients were enrolled, of whom 61 patients underwent "One-step" necrosectomy and 97 patients underwent "Step-up" necrosectomy. During the long-term follow-up period, 40 patients in the "One-step" group and 63 patients in the "Step-up" group survived. The time from disease onset to hospital admission (53.69 ± 38.14 vs 32.20 ± 20.75, P < 0.001) and to initial surgical treatment was longer in the "Step-up" than in the "One-step" group (54.38 ± 10.46 vs 76.58 ± 17.03, P < 0.001). Patients who underwent "Step-up" necrosectomy had a longer hospitalization duration (65.41 ± 28.14 vs 52.76 ± 24.71, P = 0.02), and more interventions (4.26 ± 1.71 vs 3.18 ± 1.39, P < 0.001). Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group. Although the incisional hernia incidence was higher in the "One-step" group, no significant difference was found in the composite outcomes of severe complications or death, new-onset organ failure, postoperative complications, inflammatory indicators, long-term complications, quality of life, and medical costs between the groups (P > 0.05). CONCLUSION: Compared with the "Step-up" approach, the "One-step" approach is a safe and effective treatment method with better long-term quality of life and prognosis. It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.

[Evaluation of peripheral pulmonary embolism by different thickness of CTPA imagings].

OBJECTIVE: to evaluate whether there are difference among different thickness of CTPA imagings for detection of emboli in peripheral pulmonary arteries. METHODS: CTPA Images of 97 patients with acute pulmonary embolism were divided into four series for each patient: 0.625 mm thick original transaxial soure images and 3 series of reconstructed images using the MIP technique with slab thicknesses of 1.25 mm, 2.5 mm, and 5.0 mm. The difference was compared among 4 series of CTPA images for detection of emboli in peripheral pulmonary arteries, and the agreement of 2 observers for detection of emboli in peripheral pulmonary arteries in different thickness images was tested. Chi-Square test was taken for comparison of 4 series of CTPA images for detection of emboli in peripheral pulmonary arteries. Kappa test was taken for the agreement of 2 observers for detection of emboli in peripheral pulmonary arteries. RESULTS: the average images number of 0.625 mm, 1.25 mm, 2.5 mm, 5.0 mm thickness imaging was 403, 201, 101, and 53, respectively. For detecting clots in segmental pulmonary arteries, there was statistically significant difference between 5.0 mm thick imaging and other 3 series imagings (chi(2) = 60.099, P < 0.01), but agreement of 2 observers in each series imaging was excellent (value of κ from 0.751 to 0.973).For clots in sub-segment pulmonary arteries, no statistical significant difference was observed between 0.625 mm and 1.25 mm thick imagings (chi(2) = 1.051, P > 0.05), and superior to 2.5 mm and 5.0 mm thick images (chi(2) = 151.892, 204.553, respectively, P < 0.01), but agreement of two observers in each series imaging was good (value of kappa from 0.611 to 0.935). CONCLUSION: compared with 0.625 mm thick transaxial imaging, 1.25 mm thick MIP imaging is equally sensitive for detecting emboli in peripheral pulmonary arteries, but needs fewer images and less time for image reading.

Expression of HIF-1α is a predictive marker of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

Platinum-based, arterial infusion chemotherapy as a neoadjuvant chemotherapy (NACT) followed by hysterectomy may be efficient for the treatment of locally advanced cervical cancer and improve prognosis. It is important to predict whether the NACT would be effective before it is launched. Hypoxia inducible factor-1α (HIF-1α) is the master transcriptional regulator of the cellular response to altered oxygen concentration. HIF-1α protein expression is elevated in numerous human malignancies, contributes to poor disease outcome, and has been reported to induce tumorigenesis and chemoresistance. In the present study, patients with International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer (n=59) between 2008 and 2014 were assessed for HIF-1α expression by immunohistochemistry. Tumor samples were obtained by biopsy before any treatment. A double-path chemotherapy regimen, paclitaxel (intravenous) plus cisplatin (intra-arterial injection into the uterine region), was used as NACT. The patients were then separated into two groups according to NACT response: One group comprised patients with NACT, for whom the response to treatment was efficient resulting in complete/partial remission of the tumor (CR + PR group; n=52), the other group contained patients with NACT, for whom the result of the treatment was a stable/progressive disease (SD + PD group; n=7). HIF-1α expression was tested in paraffin-embedded sections using immunohistochemistry. HIF-1α expression was significantly higher in the SD + PD group compared with the CR + PR group (P=0.029). The overall survival time was significantly longer in the CR + PR group compared with the SD + PD group (P<0.001). When the patients were divided into two groups based on HIF-1α expression levels. Low (weighted score ≤4, n=39) and high (weighted score ≥6, n=20) expression level groups; the low HIF-1α expression group was significantly more susceptible to NACT treatment (P=0.025). Cox hazard analysis revealed that a high level of HIF-1α expression and lymph node metastases were significant independent predictors of poor overall survival (P=0.025, HR=6.354; P=0.020, HR=6.909, respectively). These results indicated that the expression of HIF-1α may be able to predict the efficiency of NACT and may be considered an independent prognostic factor for stage IIB-IIIB cervical cancer.

[A comparison of the predictive values of three clinical scoring systems for suspected acute pulmonary embolism based on multidetector CT angiography].

OBJECTIVE: To explore whether acute pulmonary embolism (APE) can be quantitatively predicated early with 3 clinical scoring systems, with multidetector CT angiography (MDCTA) as the gold standard, and therefore to select a scoring system more suitable for the Chinese. METHODS: Five hundred and seventy consecutive inpatients with highly suspected APE underwent prospective MDCTA at the time of initial diagnosis. Three clinical predication scoring systems (Wells', Geneva' and revised Geneva') were used to estimate APE in low, moderate and high probability groups. Two radiologists independently reviewed the MDCTA without any clinical information. When consensus could not be reached, a third radiologist with 20-years' experience was asked to make the final decision. The threshold value for the prediction of APE by the 3 scoring systems was measured by receiver-operating-characteristics (ROC) analysis. RESULTS: APE was identified in 169 of the 570 cases. Kappa analysis for the 3 scoring systems revealed a low level of agreement: 0.269-0.374, P<0.05. The result of the Geneva score was consistent with that of the revised Geneva score, between them there was an excellent correlation. The positive predictive values of Wells, Geneva, revised Geneva scores for APE were 83.8%, 53.3%, and 61.3% respectively, while the negative predictive values were 85.0%, 80.6%, and 80.0%, respectively. ROC analysis showed that the area under curve (AUC) of Wells, Geneva and revised Geneva score for APE was 0.823 (95% CI: 0.710-0.976), 0.677 (95% CI: 0.646-0.990), and 0.661 (95% CI: 0.631-0.983), respectively. The Wells score showed the best discriminatory ability as compared to the other 2 scores. CONCLUSION: The 3 scoring systems can be used for both inpatients and emergency cases, while the Wells Score may be more accurate for Chinese people for predicting APE.

[Value of combined wells score and D-dimer test on diagnosing patients with deep venous thrombosis].

OBJECTIVE: To evaluate the value of Wells score or/and D-dimer test on diagnosing or excluding deep venous thrombosis (DVT). METHODS: Patients with suspected DVT were retrospectively analyzed. All patients underwent clinical assessment, D-dimer assay and bilateral lower extremity compression sonography within 48 hours of admission. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing DVT by Wells score, D-dimer test, and combined Wells score and D-dimer were compared. RESULTS: A total of 274 patients were analyzed. If low probability was defined as negative and moderate and high probabilities were defined as positive, the sensitivity, specificity, PPV and NPV of the Wells score were 78.4%, 66.1%, 52.3% and 86.6%, respectively. At a cut-off of 500 microg/L, the sensitivity, specificity, PPV and NPV of D-dimer test were 73.9%, 66.1%, 50.8% and 84.2%, respectively. If low probability and D-dimer < 500 microg/L were defined as negative, moderate and high probabilities and D-dimer > or = 500 microg/L were defined as positive, the sensitivity, specificity, PPV and NPV of the combined Wells score and D-dimer test were 88.3%, 76.8%, 67.1% and 92.5%, respectively. CONCLUSION: For clinical suspected DVT patients, DVT diagnosis could be reliably obtained by combined Wells score and D-dimer test.

Timing, distribution, and microbiology of infectious complications after necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdominal disease worldwide, and its incidence rate has increased annually. Approximately 20% of AP patients develop into necrotizing pancreatitis (NP), and 40% to 70% of NP patients have infectious complications, which usually indicate a worse prognosis. Infection is an important sign of complications in NP patients. AIM: To investigate the difference in infection time, infection site, and infectious strain in NP patients with infectious complications. METHODS: The clinical data of AP patients visiting the Department of General Surgery of Xuanwu Hospital of Capital Medical University from January 1, 2014 to December 31, 2018 were collected retrospectively. Enhanced computerized tomography or magnetic resonance imaging findings in patients with NP were included in the study. Statistical analysis of infectious bacteria, infection site, and infection time in NP patients with infectious complications was performed, because knowledge about pathogens and their antibiotic susceptibility patterns is essential for selecting an appropriate antibiotic. In addition, the factors that might influence the prognosis of patients were analyzed. RESULTS: In this study, 539 strains of pathogenic bacteria were isolated from 162 patients with NP infection, including 212 strains from pancreatic infections and 327 strains from extrapancreatic infections. Gram-negative bacteria were the main infectious species, the most common of which were Escherichia coli and Pseudomonas aeruginosa. The extrapancreatic infection time (9.1 ± 8.8 d) was earlier than the pancreatic infection time (13.9 ± 12.3 d). Among NP patients with early extrapancreatic infection (< 14 d), bacteremia (25.12%) and respiratory tract infection (21.26%) were predominant. Among NP patients with late extrapancreatic infection (> 14 d), bacteremia (15.94%), respiratory tract infection (7.74%), and urinary tract infection (7.71%) were predominant. Drug sensitivity analysis showed that P. aeruginosa was sensitive to enzymatic penicillins, third- and fourth-generation cephalosporins, and carbapenems. Acinetobacter baumannii and Klebsiella pneumoniae were sensitive only to tigecycline; Staphylococcus epidermidis and Enterococcus faecium were highly sensitive to linezolid, tigecycline, and vancomycin. CONCLUSION: In this study, we identified the timing, the common species, and site of infection in patients with NP.

Prevalence and Determinants of High-risk HPV Infection among 11549 Women from an Opportunistic Screening in Hubei Province.

High-risk human papillomavirus (hrHPV) infection plays an important role in the development of cervical intraepithelial neoplasia and cervical cancer. A total of 11 549 women were enrolled from the Maternal and Child Health Hospital of Hubei Province. Each participant accepted hrHPV testing and completed a self-administered questionnaire about basic information and potential risk factors. The univariable and multivariable logistic regression model was used to explore the associations between variants and hrHPV infection. Our results showed that hrHPV prevalence was 16.09% in Hubei Province, among which, hrHPV was more likely to be positive in women aged 51 years or above (OR=1.65, 95% CI: 1.28-2.14), and in women who had symptoms of bleeding after intercourse (OR=1.32, 95% CI:1.17-1.50), had first sexual intercourse at the age of 18 years or below (OR=1.33, 95% CI:1.07-1.64), had at least three male sexual partners (OR=2.50, 95% CI:2.07-3.03), and who had been diagnosed with sexually transmitted infections (OR=1.50, 95% CI:1.12-2.03). Married women (OR=0.66, 95% CI: 0.55-0.78) and women who frequently used condoms (OR=0.75, 95% CI:0.67-0.84) had a relatively lower hrHPV prevalence. This study confirms that hrHPV infection was associated with age, marital status, symptoms of intercourse bleeding, history of sexually transmitted infections, and sex-related behaviors. Above all, this study provides a baseline database prior to obtaining vaccinations for dynamic tracking of the changes in hrHPV prevalence.