[Risk prediction and function evaluation by T-cell epitope model and expression model of HLA-DPB1 mismatching in unrelated-donor hematopoietic stem cell transplantations].

Objective: To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching. Methods: A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk. Results: A total of 26 HLA-DPB1 alleles and their 3'-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052∶01 and HLA-DPB1*1119∶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant. Conclusions: TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases].

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Use of CT-based renal volumetry for the measurement of split renal function: a split glomerular filtration rate prediction model based on unilateral renal volume parameters.

AIM: To develop a split glomerular filtration rate (sGFR) prediction model based on unilateral renal volume parameters using three-dimensional (3D) computed tomography (CT) volumetry. MATERIALS AND METHODS: Clinical data (age, sex, height, weight, serum creatinine level [sCr], and sGFR measured by 99mTc-diethylene triamine pentaacetic acid nuclear renal scintigraphy with the double plasma sample method) of 67 healthy renal donors and 111 patients with hydronephrosis admitted from April 2016 to September 2021 were analysed. The split renal parenchymal volume (sRPV) and split renal calyces and pelvis volume (sRCPV) of 67 unilateral donor left kidneys and 111 hydronephrotic kidneys were measured. Statistical analysis of these parameters was performed to develop and validate the sGFR prediction model. RESULTS: sRPV (p<0.001), sRCPV (p=0.012), age (p=0.015), serum creatinine level (p=0.004), and weight (p=0.006) were significantly associated with the measured sGFR and were included in the sGFR prediction formula, which was constructed as: 68.710 + 0.093 × sRPV-0.041 × sRCPV-0.228 × W-0.219 × A-14.432 × sCr (r2 = 0.416; where A is age, W is weight). The paired difference of internal validation between the measured sGFR (42.34 ± 13.71 ml/min/1.73 m2) and the sGFR estimated by the prediction model (41.46 ± 8.99 ml/min/1.73 m2) was 0.879 ± 11.475 ml/min/1.73 m2 (p=0.492) with a 95% confidence interval of the mean difference of ±2.54 ml/min/1.73 m2. CONCLUSION: The proposed model based on sRPV and sRCPV parameters could be used for estimating split renal function of healthy renal donors and patients with hydronephrosis to some extent. Further studies are required to evaluate and rectify the model.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

[Blue light regulates the expression of brain derived neurotrophic factor in the habenula nucleus of depression-like rats induced by light deprivation].

Objective: To investigate the regulatory effect of blue light on the expression of brain derived neurotrophic factor (BDNF) in the habenula nucleus of depression-like rats induced by light deprivation. Methods: male SD rats were exposed to white light (white light control group, 20 rats) and constant darkness (depression model group, 60 rats), respectively. 18 days later rats in depression model group were randomly divided into three groups: depression model group (treated with constant darkness), blue light group (treated with blue light) and red light group (treated with red light). Rats in white light control group were kept in white light. All rats exposed to light were in a standard 12∶12 h Light/Dark condition at 20 lx for 36 days. Sucrose preference test was applied to evaluate depression-like symptoms of rats. The c-fos+cells in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus were detected. The phosphoylation of cAMP-response element binding protein (CREB) and the relative BDNF protein level in the habenula nucleus were measured. Results: Sucrose intake per kg body weight increased in rats exposed to blue light and returned to the level of control group (P>0.05). Sucrose intake per kg body weight in red light group and depression model group were lower than control group (P<0.05). More c-fos+cells were detected in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus from blue light group than those from depression model group (P<0.05). The relative BDNF protein level and the phosphoylation of CREB in the habenula nucleus from blue light group were higher than those from depression model group (P<0.05). Conclusion: Blue light could relieve depression-like symptoms in light-deprived rats. Exposure to blue light could activate neurons in the habenula nucleus to which intrinsically photosensitive retinal ganglion cells projected. Blue-light-mediated antidepressant effect might involve in the activation of CREB/BDNF signal transduction pathways in the habenula nucleus.

[A case of CHARGE syndrome confirmed by ophthalmology].

A 31-month-old female patient presented to our department of Ophthalmology in Xijing Hospital with insufficiency closed eyelid in left eye and photophobia for one month. Unsteady gait with asymmetrical face, bilateral auricle deformity and deafness could be observed on the pediatric patient. Esotropia in left eye combined, left facial nerve palsy, with binocular anisometropia was checked out after general eye examination. Echocardiography revealed that she was treated with ligation of the ductus arteriosus. A de novo pathogenic variant, c.3392T>C, was identified in CHD7 gene, which supported the diagnosis of CHARGE syndrome. (Chin J Ophthalmol, 2021, 57: 618-620).

[The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

[Expression and significance of Nek2B and ß-catenin in triple negative breast cancer].

Objective: To investigate the expression and significance of Nek2B and ß-catenin expression in triple negative breast cancer (TNBC) at molecule levels. Methods: By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and ß-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed. Results: Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/ß-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated ß-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and ß-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions: The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with ß-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/ß-catenin patients signaling pathway.

[Mechanism of renal injury and apoptosis in rats with nephrotic syndrome induced by mercury].

Objective: To investigate the relationship between renal injury and apoptosis in rats with nephrotic syndrome induced by mercury, in order to find out the pathogenesis. Methods: Forty-eight healthy male SPF-grade BN (Brown-Norway) rats were divided into the control group and the exposure group by random number table. The nephrotic syndrome was caused by subcutaneous injection of HgCl(2) (1 mg/ml) in the abdominal weight per kg of body weight. The control group was injected with the same volume of NaCl as the exposure group. Some rats were sacrificed on the 14th, 21st, 28th, and 35th days, and the serum kidney injury indicators creatinine (CRE) and urea nitrogen (BUN) were detected, and the renal tissue mercury content was detected; the in situ terminal transferase labeling technology (TUNEL) was detected Apoptosis, immunofluorescence detection of Cyt C content, Western blot detection of mitochondrial pathway apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2) , Bcl-2 related X protein (BAX) , cysteine proteinase 3 (Caspase 3) ], mitogen-activated protein kinase (MAPK) signaling pathway-related proteins[p38 mitogen-activated protein kinase (P38MAPK) , extracellular regulatory protein kinase (ERK) ] expression. Results: Compared with the control group, the BUN content in the serum of rats in the exposure group was significantly increased on days 7, 21, and 28, the CRE content was significantly increased on 21 days, the CRE content was significantly decreased on 28 and 35 days, and the organ coefficient and renal mercury content were 14 to 35 days. Significantly increased, and the differences were statistically significant (P<0.05) . Compared with the control group, rats in the exposed group showed increased glomerular stroma, tubule dilatation and other renal cell apoptosis at 14 to 35 days, and Cyt C expression was obvious in the exposed groups at 14, 21 days. Compared with the control group, the BAX content of the rats in the exposed group was significantly increased on the 21st day, the content of Caspase 3 in the rats on the 14th and 21st days was significantly increased, and the content of the P38MAPK in the 35th day was significantly increased (P<0.05) . Conclusion: HgCl(2) may cause renal cell damage through the mitochondrial pathway of apoptosis and cause nephrotic syndrome, and the MAPK signaling pathway may regulate this process and exert an inhibitory effect on apoptosis.

Vaccine-Associated Maintenance of Epithelial Integrity Correlated With Protection Against Virus Entry.

To identify the mechanisms by which human immunodeficiency virus type 1 (HIV-1) might penetrate the epithelial barrier during sexual transmission to women and the mechanisms of vaccine-associated protection against entry, we characterized early epithelial responses to vaginal inoculation of simian immunodeficiency virus strain mac251 (SIVmac251) in naive or SIVmac239Δnef-vaccinated rhesus macaques. Vaginal inoculation induced an early stress response in the cervicovaginal epithelium, which was associated with impaired epithelial integrity, damaged barrier function, and virus and bacterial translocation. In vaccinated animals, early stress responses were suppressed, and the maintenance of epithelial barrier integrity correlated with prevention of virus entry. These vaccine-protective effects were associated with a previously described mucosal system for locally producing and concentrating trimeric gp41 antibodies at the mucosal interface and with formation of SIV-specific immune complexes that block the stress responses via binding to the epithelial receptor FCGR2B and subsequent inhibitory signaling. Thus, blocking virus entry may be one protective mechanism by which locally concentrated non-neutralizing Ab might prevent HIV sexual transmission to women.

[Role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock waves therapy].

Objective: To investigate the role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock therapy. Methods: Adult male Sprague Dawley (SD) rats weighing 220-250 g were used to establish a heart failure model by ligation of the left anterior descending coronary artery. Rat models were defined by echocardiographic assessment at 4 weeks post operation and heart failure rats were randomly divided into 4 groups,namely heart failure group (HF group, 9 cases),heart failure+cardiac shock waves therapy group (HF+CSWT group, 9 cases),heart failure+inhibitor(HF+LY294002 group, 9 cases),heart failure+cardiac shock waves therapy group+inhibitor (HF+CSWT+LY294002 group, 9 cases),and another 9 sham-operated SD rats served as control group (sham group, 9 cases). At 8 weeks postoperation, echocardiography was used to evaluate cardiac function in each group,myocardial infarct size was measured by TTC staining,the apoptotic index of rats cardiomyocytes were detected by TUNEL method,the myocardial mRNA expression of apoptosis-related factor was detected by real-time quantitative PCR, the protein expression levels of PI3K/Akt signaling pathway and apoptosis-related pathways were detected by Western blot. Results: (1) Eight weeks after operation, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly lower in HF+CSWT group than in HF group (all P<0.05), left ventricular ejection fraction (LVEF) and left ventricular shortening rate (LVFS) were significantly higher in HF+CSWT group than in HF group (all P<0.05),LVEF was significantly lower in the HF+ CSWT+ LY294002 group than in HF+ CSWT group (P<0.05). (2) Myocardial infarct size was significantly lower in the HF+ CSWT group than in HF group ((5.57 ± 0.51)% vs. (25.56 ± 0.56)%, P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in HF+CSWT group ((12.90±2.34)% vs. (5.57±0.51)%,P<0.05). (3) The cardiomyocyte apoptotic index was significantly lower in the HF+CSWT group than in the HF group ((30.25±6.12)% vs. (53.85±9.89)%,P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in the HF+CSWT group ((46.12±3.42)% vs.(30.25±6.12)%,P<0.05). (4) The myocardial mRNA expression of Bcl-2 was significantly higher, while myocardial mRNA Bax and Caspase-3 expression were significantly lower in HF+CSWT group than in HF group and HF+CSWT+LY294002 group (all P<0.05). (5) The expression levels of p-Akt, Bcl-2 and pro-Caspase-3 in myocardial tissue were significantly higher in the HF+CSWT group than in the HF group and HF+CSWT+LY294002 group (all P<0.05), which were significantly lower in the HF+LY294002 group than in the HF and HF+CSWT+LY294002 groups (all P<0.05). Myocardial Bax protein expression was significantly lower in the HF+CSWT group than in the HF group and the HF+CSWT+LY294002 group (all P<0.05), which was significantly higher in the HF+LY294002 group than in the HF group (P<0.05). Conclusion: CSWT improves cardiac function and inhibits cardiomyocyte apoptosis through PI3K/Akt signaling pathways in this rat HF model.

[Two cases of occupational frostbite].

The diagnosis, treatment, operation and diagnosis of two cases of occupational frostbite diagnosed in Shandong Academy of Occupational Healthy Occupational Medicine were analyzed retrospectively. In these two patients working in a low temperature environment, the finger frostbite did not arouse enough attention, one patient did not receive timely diagnosis and treatment, and one patient received timely medical treatment, but did not receive proper treatment, which ultimately led to the adverse consequences of finger amputation. The staff under the low temperature environment should strictly carry out the low temperature operation protection standard and improve their self-protection consciousness. If frostbite occurs, they should seek medical treatment in time, which can effectively reduce the disability rate.

Comparison of pharmacodynamic effects of ticagrelor vs prasugrel in type 2 diabetes mellitus patients with coronary heart disease.

WHAT IS KNOWN AND OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y12 inhibitors with advantageous platelet inhibitory profiles. However, the pharmacodynamic differences between the two drugs in patients with T2DM remain poorly explored. METHODS: This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 7 and 30 days after randomized P2Y12 inhibitor treatment. RESULTS: The study showed a decreased platelet reactivity after use of P2Y12 inhibitors (both P < .001). On the basis of comparison between regimens, apart from the prasugrel group having a significantly higher LTA value at the 30-day time point (P = .043), there existed no significant differences in platelet reactivity at separate time points (all P > .05). As for intragroup measurements, when compared with 7-day and 30-day time points, similar platelet reactivity was documented in the ticagrelor group (both P > .05), but LTA tests showed a significant increase with time (days 7-30) in the prasugrel group (P = .050). WHAT IS NEW AND CONCLUSION: Although ticagrelor and prasugrel have similar platelet inhibitory effects in patients with T2DM, if a P2Y12 inhibitor is necessitated in patients with T2DM, ticagrelor might exert a more stable antiplatelet effect with 30-day short-term treatment.

A rating scale for the severity of Guillain-Barré syndrome.

INTRODUCTION: The objective of this study was to develop a rating scale to assess the severity of Guillain-Barré syndrome (GBS). METHODS: The preliminary rating scale, which contained 11 items, was developed by the Delphi method, and data of 258 patients were collected to evaluate it. Item analysis was accomplished by 100 patients; the additional 158 patients were used to evaluate the reliability, validity, and discriminative ability of the rating scale. The structure of the rating scale was testified by the confirmatory factor analysis and also made a further evaluation by the correlation analysis. RESULTS: The rating scale contained 10 items. The three factors mainly generalized the motor function, cranial nerve function and autonomic function. The results of reliability and validity showed that the structure of the rating scale was good (χ2 =68.25, df=32, χ2 /df=2.13, normed fit index (NFI)=0.919, non-normed fit index (NNFI)=0.936, comparative fit index (CFI)=0.96, a root mean square error of approximation (RMSEA)=0.085), and the Cronbach's α coefficient for the scale was .852, with the three dimensions ranging from .585 to .752. CONCLUSION: Reliability and validity of the rating scale are all satisfied. The scale contained the main clinical presentations of GBS, and it is suitable to evaluate the severity of GBS.

[Clinical comparison of polymethylmethacrylate and bone cement in the treatment of osteoporotic vertebral compression fractures: a retrospective study].

OBJECTIVE: To analyze the outcomes of patients with osteoporotic vertebral compression fractures treated with polymethylmethacrylate (PMMA) and GeneX bone cement in percutaneous kyphoplasty and to provide guidance in selecting the vertebral filling material for this procedure. METHODS: In this study, 86 patients with osteoporotic vertebral compression fractures treated at Peking University Third Hospital between June 2012 and June 2013 were retrospectively analyzed. The patients were followed-up with questionnaires and X-ray and CT examinations after 1 month, 3 months, 6 months, and 1 year. Postoperative conditions, including recovery rate of vertebral height, recovery rate of vertebral Cobb angle, CT data, reductions in visual analogue scale (VAS) and Oswestry scores, and postoperative complications, were evaluated. The results were analyzed using SPSS 18.0. RESULTS: According to the rank sum test, there were significant differences in the recovery rate of vertebral height, vertebral Cobb angle and vertebral volume between the two groups after 3 months, 6 months, and 1 year (P<0.05). The GeneX group had greater losses in vertebral height, Cobb angle and volume than did the PMMA group. The PMMA group had 3 cases of cement leakage and 1 case of an adjacent vertebral fracture after percutaneous kyphoplasty. The GeneX group had 2 cases of cement leakage. CONCLUSION: GeneX bone cement is similar to PMMA in terms of postoperative pain relief. As the filling material in percutaneous kyphoplasty, it is effective at maintaining vertebral height, quickly improves strength and stiffness of the vertebral body and has fewer complications. However, it is not satisfactory in maintaining long-term postoperative vertebral height. GeneX bone cement can be used as the filling material for patients with osteoporotic vertebral compression fractures in percutaneous kyphoplasty. Patients with severe osteoporosis and vertebral compression should be treated with standardized osteoporosis treatment and should try to avoid early postoperative walking exercises. Sustained vertebral filling materials, such as PMMA, are more suitable for such patients. Research into better biodegradable materials is still needed.

[Long-term outcomes of off-pump coronary artery bypass grafting].

Objective: To investigate the long-term outcomes of off-pump coronary artery bypass grafting (OPCABG). Methods: Clinical data of 1 129 consecutive patients ( 937 males and 192 females) with coronary artery disease receiving OPCABG at Department of Cardiovascular Surgery, Chinese PLA General Hospital between January 2000 and December 2015 was retrospectively analyzed.The age of patients ranged from 29 to 83 years, with a mean age of (62.0±9.6) years. The follow-up data of the patients, including the graft patency and repeated revascularization rate, were analyzed. Results: Of the 1 129 patients analyzed, 1 059 cases (93.8%) were available for follow-up for 29-192 months[with a mean time of (95.6±34.1) months]. The 5-year, 10-year, 15-year and 16-year graft patency rate of arterial graft was 96.1%, 95.4%, 93.7% and 93.2%, respectively. The 5-year, 10-year, 15-year and 16-year graft patency rate of venous graft was 92.8%, 81.4%, 70.9% and 68.3%, respectively. During the follow-up, 69 (6.11%) patients underwent repeated revascularization procedures. Conclusion: OPCABG is safe and effective with a good long-term graft patency rate.

The expression and significance of WT1 in xenotransplanted ovarian carcinoma treated by paclitaxel.

In this study, the authors investigated the expression and significance of WTl in xenotransplanted ovarian carcinoma cell SKOV3 of nude mice treated with paclitaxel. Xenotransplanted ovarian carcinoma was established in nude mice using the SKOV3 cell line. The mice were randomized into the treatment group with paclitaxel and control group with normal sodium. The sizes of the xenotransplanted tumors were measured and the tumor specimens were confirmed by routine hemotoxylin-eosin (H&E) staining. The apoptosis index was then assayed using flow cytometry. WTl and bcl-2 expression were detected with immunohistochemistry, and WT1 mRNA expression was determined by reverse transcriptase polymerase chain reaction (RT-PCR). The authors found that the growth of the xenotransplanted tumor was inhibited by paclitaxel therapy. Compared to the control group, the apoptosis rate was significantly increased in the treatment group (p < 0.05). At the same time, the expression of WTl, bcl-2 and WTI, mRNA were significantly decreased in the paclitaxel therapy group (p < 0.05). The authors conclude that the WTl gene may play an important role during apoptosis of ovarian carcinoma and the mechanism may be closely related to bcl-2.