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To systematically quantify the diagnostic accuracy and identify potential covariates affecting the performance of artificial intelligence (AI) in diagnosing orthopedic fractures.PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies on AI applications in diagnosing orthopedic fractures from inception to September 29, 2021. Pooled sensitivity and specificity and the area under the receiver operating characteristic curves (AUC) were obtained. This study was registered in the PROSPERO database prior to initiation (CRD 42021254618).Thirty-nine were eligible for quantitative analysis. The overall pooled AUC, sensitivity, and specificity were 0.96 (95% CI 0.94-0.98), 90% (95% CI 87-92%), and 92% (95% CI 90-94%), respectively. In subgroup analyses, multicenter designed studies yielded higher sensitivity (92% vs. 88%) and specificity (94% vs. 91%) than single-center studies. AI demonstrated higher sensitivity with transfer learning (with vs. without: 92% vs. 87%) or data augmentation (with vs. without: 92% vs. 87%), compared to those without. Utilizing plain X-rays as input images for AI achieved results comparable to CT (AUC 0.96 vs. 0.96). Moreover, AI achieved comparable results to humans (AUC 0.97 vs. 0.97) and better results than non-expert human readers (AUC 0.98 vs. 0.96; sensitivity 95% vs. 88%).AI demonstrated high accuracy in diagnosing orthopedic fractures from medical images. Larger-scale studies with higher design quality are needed to validate our findings.• Multicenter study design, application of transfer learning, and data augmentation are closely related to improving the performance of artificial intelligence models in diagnosing orthopedic fractures. • Utilizing plain X-rays as input images for AI to diagnose fractures achieved results comparable to CT (AUC 0.96 vs. 0.96). • AI achieved comparable results to humans (AUC 0.97 vs. 0.97) but was superior to non-expert human readers (AUC 0.98 vs. 0.96, sensitivity 95% vs. 88%) in diagnosing fractures.

Background Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. Methods Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. Results Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. Conclusion The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

Background It has been proposed that hepatitis delta virus (HDV) induces hepatic carcinogenesis by distinct molecular events compared with hepatocellular carcinoma (HCC) that is commonly induced by other hepatitis viruses. This study aimed to explore the underlying mechanism by identifying the key genes for HDV-HCC using bioinformatics analysis. Methods The GSE107170 dataset was downloaded and the differentially expressed genes (DEGs) were obtained by the online tool GEO2R. Gene otology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R packages. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Hub genes were selected by Cytoscape software according to degree algorithm. The hub genes were further validated in terms of expression and survival analysis based on public databases. Results A total of 93 commonly upregulated genes and 36 commonly downregulated genes were found. The top 5 upregulated hub genes were TFRC, ACTR2, ARPC1A, ARPC3, and ARPC2. The top 5 downregulated hub genes were CTNNB1, CCND1, CDKN1B, CDK4, and CDKN1A. In the validation analysis, the expressions of ARPC1A, ARPC3, and CDK4 were promoted in general liver cancer samples. Higher expressions of ARPC2 and CDK4 and lower expressions of CDKN1A, CCND1, and CDKN1B were associated with worse prognosis in general HCC patients. Conclusion The present study identifies a series of key genes that may be involved in the carcinogenesis of HDV-HCC and used as prognostic factors.

BackgroundMore than 70 percent of the world's population is tortured with neck pain more than once in their vast life, of which 50–85% recur within 1–5 years of the initial episode. With medical resources affected by the epidemic, more and more people seek health-related knowledge via YouTube. This article aims to assess the quality and reliability of the medical information shared on YouTube regarding neck pain.MethodsWe searched on YouTube using the keyword “neck pain” to include the top 50 videos by relevance, then divided them into five and seven categories based on their content and source. Each video was quantitatively assessed using the Journal of American Medical Association (JAMA), DISCERN, Global Quality Score (GQS), Neck Pain-Specific Score (NPSS), and video power index (VPI). Spearman correlation analysis was used to evaluate the correlation between JAMA, GQS, DISCERN, NPSS and VPI. A multiple linear regression analysis was applied to identify video features affecting JAMA, GQS, DISCERN, and NPSS.ResultsThe videos had a mean JAMA score of 2.56 (SD = 0.43), DISCERN of 2.55 (SD = 0.44), GQS of 2.86 (SD = 0.72), and NPSS of 2.90 (SD = 2.23). Classification by video upload source, non-physician videos had the greatest share at 38%, and sorted by video content, exercise training comprised 40% of the videos. Significant differences between the uploading sources were observed for VPI (P = 0.012), JAMA (P < 0.001), DISCERN (P < 0.001), GQS (P = 0.001), and NPSS (P = 0.007). Spearman correlation analysis showed that JAMA, DISCERN, GQS, and NPSS significantly correlated with each other (JAMA vs. DISCERN, p < 0.001, JAMA vs. GQS, p < 0.001, JAMA vs. NPSS, p < 0.001, DISCERN vs. GQS, p < 0.001, DISCERN vs. NPSS, p < 0.001, GQS vs. NPSS, p < 0.001). Multiple linear regression analysis suggested that a higher JAMA score, DISCERN, or GQS score were closely related to a higher probability of an academic, physician, non-physician or medical upload source (P < 0.005), and a higher NPSS score was associated with a higher probability of an academic source (P = 0.001) than of an individual upload source.ConclusionsYouTube videos pertaining to neck pain contain low quality, low reliability, and incomplete information. Patients may be put at risk for health complications due to inaccurate, and incomplete information, particularly during the COVID-19 crisis. Academic groups should be committed to high-quality video production and promotion to YouTube users.

Background Ovarian squamous cell carcinoma (SCC) is a rare cancer with possible poor survival, however no direct evidence supports this viewpoint and the independent prognostic factors are controversial. Patients with ovarian SCC and serous carcinoma (SC) who were diagnosed between 2004 and 2016 were selected using the recent released SEER database. Propensity score matching was used to balance the characteristics of the two groups. The difference of survival between patients with ovarian SCC and SC was explored using Kaplan-Meier method. Cox regression analyses were performed to further identify the independent prognostic factors among patients with ovarian SCC. Results Of 15,286 patients (15,106 SC cases and 180 SCC cases), 304 were identified in the matched cohort (200 SC cases and 104 SCC cases). The overall survival and cause-specific survival for patients with SCC were significantly poorer (Plog-rank Conclusions The prognosis of ovarian SCC is worse than ovarian SC. Older age at diagnosis, advanced disease stage, larger tumor size and bilateral malignancy are the independent risk factors for poor survival.

Background:. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear. Methods:. An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting. Results:. The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone. Conclusions:. PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

Background To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. Methods Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. Results Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). Conclusions For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. Trial registration This project has been registered in the Chinese Clinical Trial Registry (ChiCTR1800019978).

Background Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. Methods The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004–2011, while the validation dataset included 407 patients diagnosed in 2012–2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. Results Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693–0.710) and 0.699 (95% CI: 0.682–0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620–0.639) and 0.607 (95% CI: 0.588–0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score ˃ 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. Conclusions Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.

The rs36084323 A > G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A > G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR = 0.89, 95%CI:0.81–0.97, P = 0.008, I2 = 48.8%; GG vs. AA, OR = 0.79, 95% CI:0.66–0.94, P = 0.008, I2 = 48.7%; GG/AG vs. AA, OR = 0.87, 95%CI:0.76–0.98, P = 0.017, I2 = 34.9%; GG vs. AG/AA, OR = 0.85, 95%CI:0.75–0.97, P = 0.027, I2 = 40%) and in the patients with EOC(AG vs. AA, OR = 0.69, 95%CI:0.54–0.90, P = 0.005, I2 = 0%; GG/AG vs. AA, OR = 0.67, 95%CI:0.52–0.85, P = 0.001, I2 = 0). Meta-regression showed that ethnicity (P = 0.029) but not cancer types (P = 0.792), source of controls (P = 0.207) or ample size (P = 0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A > G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.

BACKGROUND Gut bacterial diversity is decreased in a proportion of patients with septic shock. We attempted to validate the hypothesis that low bacterial diversity increases the risk of mortality. MATERIAL AND METHODS All patients with septic shock seen at 2 medical center from 2016 through 2019 were included in this cohort study. Total DNA was isolated from stool, and high-throughput sequencing was performed. Clinical data were extracted from patient medical records and hospital databases. Patients were grouped by gut microbiota bacterial diversity (measured by Shannon diversity index) on presentation. We used logistic regression analysis to evaluate the risk of 28-day mortality in septic patients with low Shannon diversity index. RESULTS Of the 150 patients enrolled in this study, low bacterial diversity (Shannon index

Nephrotoxicity limits the use of cisplatin (CP) in cancer therapy; however, current clinical measures of renal health do not reflect low degrees of kidney injury. Therefore, discovering new biomarkers for CP-induced acute kidney injury (AKI) is essential for monitoring kidney health during therapy. To identify novel candidate biomarkers in urine for reduced renal function due to CP therapy, we conducted a pilot study on cancer patients eligible for CP treatment. Urine from 30 patients was collected before (baseline) and after 3d of intravenous CP infusion. Urine samples were subjected to Isobaric Tag for Relative Absolute Quantitation (iTRAQ) analysis. Biological roles and pathways for the proteins with altered urine concentrations were identified using bioinformatic tools ITRAQ analysis detected 1411 proteins, 12 of which showed significantly altered levels. Growth differentiation factor-15 (GDF15), leucine-rich alpha-2-glycoprotein 1 (LRG1), and secreted phosphoprotein 1 (SPP1/ osteopontin, OPN) were identified as potential candidate markers by proteomic analysis and were validated by ELISA in another 30 patients and in a CP-induced AKI mouse model. Therefore, GDF15, LRG1, and SPP1 may be applied as novel candidate urinary markers of kidney injury after cisplatin treatment. These findings may facilitate the development of new methods to monitor kidney function, particularly in CP-based chemotherapy. SIGNIFICANCE: Cisplatin is pivotal for cancer treatment; however, nephrotoxicity limits its use. Clinical measures for renal health are not reflective of early signs of acute kidney injury. Thus, new indicators of the state of renal health following cisplatin treatment will have to be discovered. This study reports the use of proteomics to mine for candidate markers of kidney injury in the urine of patients undergoing treatment with cisplatin. Results were experimentally validated using patient urine and a mouse model of cisplatin-induced acute kidney injury. The novel candidate biomarkers reported in this study may be used for the non-invasive monitoring of renal health and in mitigating the side-effects of cisplatin during the course of cancer treatment.

This study aims to investigate the human immunodeficiency virus (HIV) transmission rate in HIV serodiscordant couples, in addition to the relevant influencing factors. From January 1999 to August 2016, patients with HIV/AIDS (index cases) along with their fixed partners were registered and monitored to determine the rate of HIV transmission between couples, as well as relevant influencing factors. A total of 231 HIV-positive couples were investigated, of these, 45-negative (19.48%) partners were infected with HIV via sexual transmission prior to diagnosis of the first case detected in couples. After diagnosis, the transmission rate between spouses was 0.39 per 100 person-years (2/507.7), and the cumulative transmission rate was 1.08% (2/186), which was significantly lower than the transmission rate before diagnosis (χ2 = 35.714, P < 0.001). Among the 119 HIV/AIDS patients who received antiretroviral therapy (ART), the transmission rate was 0 (0/119), whereas the transmission rate was 2.99% (2/67) in HIV/AIDS patients who did not receive ART. In addition, HIV transmission rate in serodiscordant couples was high prior to diagnosis of the index case. However, following diagnosis, the transmission rate was reduced, and the risk of transmission in the index case with antiviral treatment was null. Therefore, a prompt intervention in HIV discordant couples with ART of index case is vital to reduce the risk of HIV transmission.

Peptide-spectrum matches (PSM) scoring between the experimental and theoretical spectrum is a key step in the identification of proteins using mass spectrometry (MS)-based proteomics analyses. Efficient protein identification using MS/MS data remains a challenge. The strategy of using RNA-seq data increases the number of proteins identified by re-constructing the custom search database and integrating mRNA abundance into the false discovery rate of post-PSM. However, this process lacks an algorithm that can allow the incorporation of mRNA abundance into the key scoring model of PSM. Therefore, we developed a novel PSM scoring model, which incorporates mRNA abundance for improved peptide and protein identification. In the new algorithm, abundance information of mRNA was transformed to the prior probability of protein identification and integrated to re-score in PSM using the binomial probability distribution model. Compared with other algorithms using five MS/MS datasets, the results showed that the least improvement ratios of peptide and protein groups were 3.39%-9.79% and 0.48%-8.16% in different datasets (human, rat, zebrafish, yeast, and Arabidopsis thaliana). The new strategy offers an effective solution for MS-based identification of peptides and proteins. SIGNIFICANCE: The new algorithm identifies proteins by quantifying mRNA abundance (FPKM) and incorporating it into a scoring model for peptide-spectrum matches. It is important to improve peptide and protein identification from MS/MS datasets in proteomics research.

Background The objective of the study was to observe the efficacy and safety of pulsatile administration of high-dose gefitinib or erlotinib in patients with advanced non-small cell lung cancer (NSCLC) with secondary drug resistance to standard doses of tyrosine kinase inhibitor (TKI) treatment. Materials and methods We recruited 42 NSCLC patients from our hospital, between August 2014 and December 2015, who had experienced drug resistance after one year of conventional treatment with gefitinib or erlotinib. The gefitinib group (29 patients) received one dose of 1000 mg gefitinib every four days. The erlotinib group (13 patients) received one dose of 450 mg erlotinib every three days. Treatments continued until disease progression according to Response Evaluation Criteria In Solid Tumors 1.1 or development of intolerable toxicity. Results Median progression-free survival (PFS) was 30 months (gefitinib vs. erlotinib: 31 vs. 24 months; P > 0.05). After high-dose pulsatile administration, eight patients achieved a partial response (PR), 11 had stable disease (SD), and 23 had progressive disease (PD; relative risk 19.0%; disease control rate 45.2%; median PFS six months). Patients were categorized based on epidermal growth factor receptor gene mutation: exon 19 (no patients achieved complete response [CR], 4 PR, 6 SD, and 17 PD) and exon 21 mutation groups (no patients achieved CR, 4 PR, 5 SD, and 6 PD). Conclusion High-dose TKI pulsatile treatment is safe, efficient, and can improve prognoses for certain patients with advanced NSCLC.

To explore a method of modified incision to prevent the postoperative spinal lateral angulation via anterior approach for lumbar fracture.A total 40 patients with lumbar fracture from January 2016 to Jun 2017 were internalized in the study. Including 28 males and 12 females, aged from 27 to 68 years with an average of (39.5±14.9) years. Among them, 28 cases caused by high fall, 9 cases by heavy injury, 3 cases by traffic accidents; and 35 fractures were located at L₁,4 at L₂,1 at L₃. All the fractures were type A based on AO classification. According to Frankel classify of spinal cord injury, 5 cases were grade A, 1 case was B, 10 cases were C, 15 cases were D, 9 cases were E. The patients were divided randomly into modified incision groups and routine incision groups. All patients were treated with decompression, internal fixation and titanium mesh supported bone graft fusion via anterior approach. All the internal fixation materials were ANTERIOR (Medtronic Inc). Incision direction and incision plane were improved in modified incision groups. The coronal Cobb angle and the angle between the vertebral screw and the corresponding endplate were analyzed before and after operation.Pre-and post-operative coronal Cobb angles were (1.20±3.26) °, ( 2.16±3.55)° in modified incision groups and(1.22±4.42)°, (3.91±3.78)° in routine incision groups respectively. And there was no statistical difference before operation, and there was statistical difference after operation between two groups(The improvement of incision direction and plane can effectively prevent the postoperative spinal lateral angulation via anterior approach for lumbar fracture.

To measure imaging data of occipitocervical angle in healthy people at different ages by X-ray.One hundred and fifty asymptomatic volunteers(75 males and 75 females) aged from 20 and 70 years old with an average of(44.83±13.88) years old were divided into 5 groups according to different ages(20 to 29 years old, 30 to 39 years old, 40 to 49 years old, 50 to 59 years old and 60 to 70 years old), and 30 people in each group. All people underwent lateral radiography of neck on neutral position. McGregor line (the lowest connection line between upper margin of hard palate and occipital scales of plating), occipitocervical angle(OCA) formed by edge of C2 vertebral body, takami's occipitocervical angle formed between connection line of posterior marginal of C2 vertebral body and parallel lines of hard palate were collected. The data were performed statistical analysis according to gender and different ages, and analyzed correlation between OCA and TOCA.OCA of 75 males at different ages were (14.71±3.09)° and(14.22±4.27)° in 75 females. TOCA of 75 males at different ages were (90.50±4.63)° and (90.57±6.67) ° in 75 females. There were no statistical difference in OCA and TOCA in people at different ages(The paper provided normal values for occipitocervical angle in population of southwestern China between 20 and 70 years old, and results may be useful for posterior occipitocervical fixation and fusion.

To compare the hemostatic effect between absorbable hemostatic fluid gelatin (HFG) and absorbable gelatin sponge(GS) during operation of unilateral open-door cervical expansive laminoplasty.The clinical data of 83 patients underwent unilateral open-door cervical expansive laminoplasty from February 2014 to May 2016 were retrospectively analyzed. According to the used hemostatic materials, patients were divided into two groups. In HFG group, there were 30 males and 11 females, ranging in age from 29 to 81 years, with an average of(55.6±11.6)years; 14 cases were simple cervical spinal stenosis, 9 were cervical spinal stenosis and ossification of posterior longitudinal ligament, and 18 were cervical spinal stenosis complicated with multiple cervical disc herniation. And in GS group, there were 32 males and 10 females, ranging in age from 36 to 78 years, with an average of (55.4±11.1) years; 12 cases were simple cervical spinal stenosis, 10 were cervical spinal stenosis complicated with ossification of posterior longitudinal ligament, and 20 were cervical spinal stenosis complicated with multiple cervical disc herniation. There was no significant difference in the age, gender, and disease categories of patients between two groups (The average operative time, intraoperative bleeding, and postoperative drainage in HFG group were(137.2±30.0) min, (156.1±74.6) ml, and (212.1±67.6) ml, respectively; and in GS group were (154.8±33.5) min, (242.9±120.7) ml, and(303.3±115.5) ml, respectively. There were significantly differences in above items between two groups(Compared with GS, HFG can obviously decrease operative time, intraoperative bleeding, and postoperative drainage. It is a safe and effective hemostatic material for the operation of unilateral open-door cervical expansive laminoplasty.

Background The precise role of innate immune responses in the early stage of traumatic spinal cord injury (SCI), especially those mediated by natural killer (NK) cells, is poorly understood. Methods The frequency and phenotype of NK cells from traumatic SCI patients and healthy controls were assessed by flow cytometry. ELISA assay was used to detect the production of a series of cytokines, neurotrophins, and neurohormones in plasma samples. In vitro cell culture was performed to observe brain-derived neurotrophic factor (BDNF)-induced NK cell activation. Results A significant increase in the NK cell frequency and the presence of NK cells with the activated phenotype was observed, as reflected by the enhanced expression of CD69, HLA-DR, NKG2D, and NKp30 on the NK cells, in traumatic SCI patients within 24 h of injury, compared to case for the healthy controls. Meanwhile, a higher level of BDNF, a member of the neurotrophin family, was observed in the plasma samples of the SCI patients; the elevated level of BDNF was strongly and positively correlated with the percentage of NK cells during the early stage of traumatic SCI. Furthermore, the expression of CD69 and NKp30 on the NK cells increased following stimulation with BDNF for 24 h in vitro , which is consistent with the in vivo observation in SCI patients. Conclusion Collectively, our findings demonstrate the activation of NK cells within 24 h after traumatic SCI, and reveal a novel role of BDNF in regulating NK cell activation.

To investigate the radiosensitizing effect and mechanism of action by the natural product Paeonol on lung adenocarcinoma both in vitro and in vivo.Two lung adenocarcinoma cell lines (human lung adenocarcinoma cell line A549 and mouse Lewis lung carcinoma (LLC) cell line) were chosen for this research. In order to select the experimental concentrations of Paeonol, cytotoxicity was determined using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide) assay. A clonogenic assay was performed to measure the radiosensitizing effects. Apoptosis was determined by the Tunel (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) assay and flow cytometry. Protein expression was analyzed by Western blotting. To test the radiosensitizing effect in vivo, a transplanted tumor model was established.The MTT assay showed that Paeonol inhibited proliferation of cells. Paeonol concentration ranged from an IC5 (5% inhibiting concentration) to an IC20 and was used at non-toxic concentrations for subsequent experiments. The clonogenic assay showed that Paeonol enhanced the radiosensitivity of cells. Data from the Tunel assay and flow cytometry verified that Paeonol enhanced radiation-induced apoptosis. Paeonol inhibited the activation of the PI3K/AKT (Phosphatidylinositol 3-kinase/ Protein Kinase B) pathway and down-regulated the expression of COX-2 (Cyclooxygenase-2) and Survivin. Paeonol (1718 mg/kg) combined with 10 Gy irradiation inhibited the growth of a transplanted tumor model in vivo, resulting in the longest tumor growth time, tumor growth delay and the highest inhibition ratio when compared with the radiotherapy alone group.It is reported for the first time that Paeonol has a radiosensitizing effect on lung adenocarcinoma both in vitro and in vivo. This effect could be related to the augmentation of radiation-induced apoptosis and the inhibition of the PI3K/Akt signalling pathway and its downstream proteins: COX-2 and Survivin.

To explore the effectiveness of absorbable hemostatic fluid gelatin in preventing postoperative cerebrospinal fluid leakage.The clinical data of 17 patients with dura mater tear were retrospectively analyzed from March to September in 2003. There were 16 males and 1 female, aged from 16 to 67 years old with an average of (39.6 ± 15.4) years. The injury site was at cervical vertebrae in 1 case, thoracic vertebrae in 9 cases, thoracolumbar junction in 4 cases, lumbar vertebrae in 3 cases. There were burst fracture in 4 cases and fracture-dislocation in 13 cases. According to ASIA grade, 12 cases were grade A, 2 cases were grade B, 2 cases were grade D, 1 case were grade E. Two cases caused by traffic accident, 10 by high falling, 4 by heavy parts crash, 1 by stairs fell during the earthquake. Absorbable hemostatic fluid gelatins were used to plug the dura mater tear,in order to prevent postoperative cerebrospinal fluid leakage. Postoperative drainage were recorded every day.Of 17 patients, 15 cases did not develop with cerebrospinal fluid leakage. Two cases develop with cerebrospinal fluid leakage after operation and their drainage were removed at 6 to 7 days after operation. In all cases, no complications related with cerebrospinal fluid leakage occurred, such as headache, dizzy, fever,neck resistance, rash, incision disunion, incision infection, hematoma, neurologic symptoms aggravation. No abnormal phenomena was found on incision surrounding at follow-up of 9 months.Using absorbable hemostatic fluid gelatin to plug the dura mater tear during operation is an effective method in preventing postoperative cerebrospinal fluid leakage.

The purpose of this study was to investigate the phenotypic and molecular characterization of a novel plasmid-mediated AmpC-type β-lactamase in Klebsiella pneumoniae E701 isolated from Anhui province in China. In comparison with the ACT-1, sequence analysis revealed that there were 43 point mutations in the coding gene, and 10 of which led to amino-acid substitution. Resistance could be transferred by conjugation or transformation with plasmid DNA into E. coli JM109, which was due to the production of a β-lactamase with an isoelectric point of 8.4 named ACT-6. Cloning, expression, purification and kinetics were carried out to study the characterization of the novel AmpC-type β-lactamase. The results of MIC determinations and substrate profiles showed there was no significant difference in the activities of the novel enzyme and ACT-1. Moreover, the class 1 integron and the whole open reading frame of the novel AmpC-type β-lactamase from K.pneumoniae E701 were detectable in the same size plasmid. This is the first report on the emergence of the novel ACT-6 type β-lactamases in K. pneumoniae.

Murine studies have shown that immunological targeting of fibroblast activation protein (FAP) can elicit protective immunity in the absence of significant pathology. Fibroblast activation protein is a product overexpressed by tumor-associated fibroblasts (TAF) and is the predominant component of the stoma in most types of cancer. Tumor-associated fibroblasts differ from normal adult tissue fibroblasts, and instead resemble transient fetal and wound healing-associated fibroblasts. Tumor-associated fibroblasts are critical regulators of tumorigenesis, but differ from tumor cells by being more genetically stable. Therefore, in comparison to tumor cells, TAF may represent more viable therapeutic targets for cancer immunotherapy. To specifically target TAF, we constructed a DNA vaccine directed against FAP. This vaccine significantly suppressed primary tumor and pulmonary metastases primarily through CD8+ T-cell-mediated killing in tumor-bearing mice. Most importantly, tumor-bearing mice vaccinated against FAP exhibited a 1.5-fold increase in lifespan and no significant pathology. These results suggest that FAP, a product preferentially expressed by TAF, could function as an effective tumor rejection antigen. (Cancer Sci 2010; 101: 2325–2332)

Trichloroethylene (TCE), a major chemical hazard during occupational exposure, can cause obvious skin lesions, including irritant reactions and dermatitis. Nitric oxide (NO) synthesized by nitric oxide synthase (NOS) is involved in a broad array of pathogenesis of skin inflammatory and immune responses. To understand the mechanisms of TCE-induced dermatoxicity, we investigated the effects of TCE on NO production and NOS mRNA expression in cultured normal human epidermal keratinocytes (NHEK). Cells were treated with TCE (0 mM, 0.125 mM, 0.25 mM, 0.5 mM, 1.0 mM, 2.0 mM) for 4 h, and then incubated for 12 h, 24 h, 48 h and 72 h. At each given time point, NO production were evaluated indirectly by measuring nitrite plus nitrate concentration in the culture medium using Griess reaction, as well as cell viability determined by MTT test, iNOS and cNOS activities assayed with a NOS activity detecting kit. The expression of iNOS and cNOS mRNA was detected using RT-PCR. TCE decreases cell viability and enhance NO production from NHEK in concentration- and time-dependent manner. Aminoguanidine (AG), an inhibitor of NOS, can prevent NO production and cell viability decrease in NHEK by TCE induced. Change to NO production was accompanied by increased activities of both types of NOS, but the iNOS activity accounted mainly for the TCE-induced NO production. RT-PCR detection showed that NHEK expressed both iNOS and cNOS mRNA by TCE exposure. Whereas a concentration- and time-dependent up-regulation of the mRNA expression was observed for iNOS and cNOS following TCE exposure, changes to iNOS were more marked. These results suggest that TCE caused increase in NO production, attributed to activation of iNOS as well as cNOS, and expression of iNOS and cNOS mRNA. These cellular changes may contribute to the pathological and physiological features of TCE-induced erythema and skin inflammation.

Numerous epidemiological studies have evaluated the association of Glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with the risk of skin cancer. However, the results remain inconclusive. To derive a more precise estimation of the association between the GSTP1 Ile105Val polymorphism and skin cancer risk, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association of GSTP1 Ile105Val polymorphism with skin cancer risk. Thirteen case-control studies in nine articles, which included a total of 1504 cases and 2243 controls. Overall, we found that GSTP1 Ile105Val polymorphism was not associated with skin cancer risk. Furthermore, subgroup analysis by histological types showed that GSTP1 Ile105Val polymorphism was associated with risks of malignant melanoma under the dominant model (Val/Val + Val/Ile vs. Ile/Ile: OR 1.230, 95 % CI 1.017-1.488, P = 0.033). However, lack of association between GSTP1 Ile105Val polymorphism and BCC and SCC risk in all genetic models. Our meta-analysis suggested that the GSTP1 Ile105Val polymorphism might be associated with increased risk of malignant melanoma in Caucasian population.

Apoptosis resistance in hepatocellular carcinoma (HCC) is one of the most significant factors for hepatocarcinogenesis and tumor progression, and leads to resistance to conventional chemotherapy. It is well known that inhibitor of apoptosis proteins (IAPs) play key roles in apoptosis resistance, it has become an important target for antitumor therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, targeted IAPs, leading to the inhibition of apoptosis resistance. To accomplish this, we first observed that four members of IAPs (cIAP-1, cIAP-2, survivin, and XIAP) were overexpressed in human HCC tissue. Interestingly, melatonin significantly inhibited the growth of HepG2 and SMMC-7721 cells and promoted apoptosis along with the downregulation of survivin and XIAP, but had no effect on the expression of cIAP-1 and cIAP-2. These data suggest that the inhibition of survivin and XIAP by melatonin may play an important part in reversing apoptosis resistance. Notably, cIAP-1, survivin and XIAP were significantly associated with the coexpression of COX-2 in human HCC specimens. Melatonin also reduced the expression of COX-2 and inhibited AKT activation in HepG2 and SMMC-7721 cells. Inhibition of COX-2 activity with the selective inhibitor, NS398, and inhibition of AKT activation using the PI3K inhibitor, LY294002, in tumor cells confirmed that melatonin-induced apoptosis was COX-2/PI3K/AKT-dependent, suggesting that the COX-2/PI3K/AKT pathway plays a role in melatonin inhibition of IAPs. Taken together, these results suggest that melatonin overcomes apoptosis resistance by the suppressing survivin and XIAP via the COX-2/PI3K/AKT pathway in HCC cells.

Chemoresistance in hepatocellular carcinoma (HCC) is associated with multiple cellular responses to environmental stresses, such as nutrient deprivation and hypoxia. Nevertheless, whether ER stress resulting from nutrient deprivation and tumor hypoxia contributes to drug resistance remains unclear. Melatonin increased the efficacy of chemotherapeutic drugs in hepatocellular carcinoma in our previous studies. However, the effects of melatonin on endoplasmic reticulum (ER) stress-induced resistance to chemotherapeutic agents in HCC have not been tested. The effect of the endoplasmic reticulum (ER) stress response during resistance of human hepatocellular carcinoma cells against doxorubicin was investigated in this study. Pretreatment of HepG2 and SMMC-7721 cells (two human hepatocellular carcinoma cell lines) with tunicamycin, an ER stress inducer, drastically decreased the rate of apoptosis generated by doxorubicin. Interestingly, co-pretreatment with tunicamycin and melatonin significantly increased apoptosis induced by doxorubicin. Simultaneously, the expression of phosphorylated AKT (p-AKT) was elevated in HepG2 and SMMC-7721 cells given tunicamycin but reduced in the presence of melatonin. Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. These results demonstrate that melatonin attenuates ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by down-regulating the PI3K/AKT pathway, increasing the levels of CHOP and decreasing the levels of Survivin.

BACKGROUND: A number of studies have investigated the association between Helicobacter pylori (H. pylori) infection and the prognosis of gastric cancer (GC), with inconsistent and inconclusive results. We performed a meta-analysis to derive a more precise estimation of the association. METHODOLOGY/PRINCIPAL FINDINGS: A systematic search of PubMed, EMBASE, Cochrane and Chinese wanfang databases was performed with the last search updated on February 19, 2013. The hazard ratio (HR) and its 95% confidence interval (95%CI) were used to assess the strength of association. A total of 12 studies including 2454 patients with GC were involved in this meta-analysis. The pooled HR was 0.71 (95%CI: 0.57-0.87; P = 0.001) for OS and 0.60 (95%CI: 0.30-1.18; P = 0.139) for DFS in GC patients, respectively. The protective role of H. pylori infection in the prognosis of GC was also observed among different subgroups stratified by ethnicity, statistical methodology, H. pylori evaluation method and quality assessment. There was no evidence of publication bias. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests a protective role for H. pylori infection in the prognosis of GC. The underlying mechanisms need to be further elucidated, which could provide new therapeutic approaches for GC.

Endoplasmic reticulum stress-mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress-induced apoptosis in HCC have not been tested. Differences in ER stress-induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). Significant differences were observed in the rate of apoptosis between HepG2 cells (hepatoma cells) and HL-7702 cells (normal human hepatocyte cells). The expression of cyclooxygenase-2 (COX-2) was increased in HepG2 cells but not in HL-7702 cells. Furthermore, down-regulation of COX-2 expression using the COX-2 inhibitor, celecoxib, increased tunicamycin-induced apoptosis concomitant with the up-regulation of pro-apoptotic transcription factor CHOP (GADD153) and down-regulation of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, suggesting that inhibition of COX-2 sensitized human hepatoma cells to ER stress-induced apoptosis. Interestingly, co-treatment with tunicamycin and melatonin also decreased the expression of COX-2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl-2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress-induced apoptosis by down-regulating COX-2 expression, increasing the levels of CHOP and decreasing the Bcl-2/Bax ratio.

Neurological endemic cretinism, resulting from severe iodine deficiency, is characterized by mental deficiency, deafmutism, and a spastic-rigid motor disorder. Its neuropathology and pathophysiology have been investigated very little. We report the clinical and magnetic resonance imaging brain scan findings of 3 adult Chinese cretins. All show an apparent magnetic resonance imaging abnormality in the globus pallidus and substantia nigra, with hyperintensity on T1-weighted images and hypointensity on T2-weighted images. The motor abnormality, characterized by truncal and proximal limb-girdle rigidity and spasticity, with relative sparing of the hands and feet, is analogous to other extrapyramidal disorders. Endemic cretinism is a unique form of cerebral palsy of potential interest for students of human neuromotor development.

Cholesystolithiasis is often associated with common bile duct stones (CBDS). In order to assess the choice of surgery in terms of effectiveness and complications in the treatment of CBDS, we have compared three surgical procedures, viz., laparoscopic choledocholithotomy T-tube drainage (LCH-TD), laparoscopic cholecystectomy with endoscopic sphincterotomy (LC-EST), and the traditional open choledocholithotomy with T-tube drainage (OCHTD). This study is a retrospective comparative analysis of LCH-TD (77 patients), LC-EST (43 patients), and OCHTD (60 patients) for CBDS. The success of the surgical procedures was assessed in terms of recovery duration, hospitalization, and post-operative complications. Both the micro-invasive procedures, LCH-TD and LC-EST, with a success rate of 92.5%, are found to be superior to the traditional OCHTD. Between the two micro-invasive procedures, patients in LCH-TD group had shorter operation time and hospital stay, and fewer post-operative complications. Although the size of the stones is comparable between these two groups, the CBD diameter was significantly larger in patients who underwent LCH-TD. In comparison to OCHTD, both LCH-TD and LC-EST are micro-invasive, safe, and suitable for routine use in patients with CBDS. Moreover, when the CBD diameter is wider than 1 cm, LCH-TD is strongly advocated.

To retrospectively investigate the risk factors, distribution, antibiotic resistance of infection with Gram-positive (G+) bacteria in an intensive care unit (ICU), so as to provide the reference for clinical prevention and treatment.A retrospective analysis of clinical data of 83 patients with G+ bacteria infection in ICU from January 2003 to December 2008 was done.Of the 125 strains of G+ bacteria from 83 patients, Staphylococcus was the main organism (63.2%, 79/125). The prognosis of the patient was related with surgical operation (chi2=9.107, P=0.003), gastric intubation (chi2=4.053, P=0.044), complication (chi2 5.908, P=0.015) and the use of immunosuppressant (chi2=5.761, P=0.016). Multi-bacterial infection was related with surgery (chi2=8.847, P=0.003) and tracheostomy (chi2=10.445, P=0.001). The antibiotic susceptibility test in vitro showed that G+ bacteria displayed multi-resistance to antibiotics, but all of G+ bacteria were sensitive to vancomycin (resistance rate was 0).Staphylococcus was the most common pathogen of G+ bacterial infection in ICU. Further surveillance of bacterial resistance is warranted in ICU, and antimicrobial drugs should be used according to the result of susceptibility test. Taking account of the antibiotic resistance and risk factors of G+ bacteria infection in ICU, the infection could be controlled and the death rate could be cut down when appropriate measures are taken.

To study the risk factors of infection of extended-spectrum beta-lactamases (ESBL)-producing strains and drug resistance of Enterobacteriaceae that infected burn patients.A retrospective study was performed on clinical information of 92 patients with Enterobacteriaceae infection in our burn unit from January 2001 to December 2008. The distribution and drug resistance of Enterobacteriaceae, and the detection rate, drug resistance of ESBL-producing strains, and its risk factors of nosocomial infection were analyzed. Data were processed with Chi-square test.One hundred and nine strains of Enterobacteriaceae were isolated, with 38 (34.9%) strains of Enterobacter cloacae, 25 (22.9%) strains of Escherichia coli, 22 (20.2%) strains of Klebsiella pneumoniae, 13 (11.9%) strains of Proteus mirabilis, and 11 (10.1%) other strains of Enterobacteriaceae. Enterobacteriaceae were moderately or highly resistant to antibiotics except imipenem, resistance rate of which was less than 8.0%. ESBL-producing strains accounted for 44.0% in Escherichia coli, and 77.3% in Klebsiella pneumoniae. Drug-resistance rate of ESBL-producing strains to antibiotics was obviously higher than that of non ESBL-producing strains. Length of hospital stay longer than 20 days, and use of the third-generation cephalosporin longer than 5 days, quinolone antibiotics longer than 7 days, and topical antibiotics longer than 5 days were the risk factors of nosocomial infection caused by ESBL-producing strains, comparing with non ESBL-producing strains, the difference was statistically significant (with chi2 value respectively 5.491, 4.441, 15.186, 4.938, P values all below 0.05).Enterobacteriaceae strains in burn unit of our hospital are highly drug resistant, with high lactamase-producing rates, calling for intense monitor to control the risk factors that predispose the infection of ESBL-producing strains in order to lower the infection rate.

To measure the linear polyethylene wear with use of a computer-assisted two-dimensional method, and to evaluate the relationship between wear and long-term clinic-radiological findings.Between December 1991 and December 1995, the senior author performed 40 primary total hip arthroplasties with use of H/G porous-coated acetabular component. Radiographs of 40 H/G cementless total hip arthroplasties were examined for osteolysis, radiolucent line, cup migration and so on. To measure the linear polyethylene wear, migration in the femoral head center relative to the cup shell center was calculated on digitized consecutive radiographs with special computer software program.The minimum follow-up was 10 years. Total linear wear was 2-8 mm, the mean rate of linear polyethylene wear was (0.32+/-0.31) mm/year. Twelve acetabular components (30%) were revised at an average follow-up point of 12 years. Three types of polyethylene liner failure were identified: wear-through of the polyethylene liner with resultant metallosis (5 hips), excessive wear necessitating revision (5 hips), and polyethylene liner dissociation without gross evidence of wear (2 hips).High wear rates and femoral and acetabular osteolysis have been and still are the main problems in uncemented total hip replacement. There is clear relationship between wear and acetabular osteolysis or loosening of the prostheses. The poor long-term results with these uncemented total hip arthroplasties illustrate the necessity of regular radiographic evaluation in order to detect osteolysis and liner failure, which are both generally asymptomatic until catastrophic failure appears.

To explore the potential mechanism of trichloroethylene (TCE)-induced apoptosis in normal human epidermis keratinocyte (NHEK) by assaying the Caspase activities, mitochondrial membrane potential (DeltaPsim) and apoptosis in vitro.NHEK was exposed to TCE and Caspases-3, 8 and 9 activities were determined using a commercial assay kit. Apoptosis and DeltaPsim were detected by flow cytometry (FCM) after double-stained with annexin-V and PI, Rh123 and PI respectively. NHEK was pretreated with inhibitor of Caspase-3 or 9 to verify the activation of Caspases by TCE treatment.Various dose of TCE exposure could increase the Caspases-3 and 9 activities in dose- and time-dependent way. There was marked difference between TCE-treated group and control at 12 or 24 h. But no significant influence of Caspase-8 activity was evoked. 0.125, 0.25, 0.5, 1.0 and 2.0 mmol/L TCE treated NHEK 4 h then cultured for 12 h. Annexin-V(+)/PI(-) proportion were (20.1 +/- 4.1)%, (30.0 +/- 7.5)%, (42.1 +/- 8.2)%, (56.0 +/- 6.1)% and (79.1 +/- 4.3)% respectively. There was marked difference between TCE-treated group except for 0.125 mmol/L and control (9.4 +/- 3.0)% (all P0.05). FITC(+)/PI(-) proportion were marked positive correlation with Caspase-3 and 9 activities, r = 0.786, 0.736 (both P0.05). Caspase-3 activities had also a marked positive correlation with Caspase-9 activities, r = 0.845 (P0.05). There was no correlation with Caspase-8 activities. Pretreatment for 1 h with 100 micromol/L Z-DEVD-FMK decreased the Caspase-3 activities from (0.963 +/- 0.043) to (0.349 +/- 0.045) nmol pNA * min(-1) * ml(-1), annexin-V(+)/PI(-) proportion decreased from (80.0 +/- 5.5)% to (16.3 +/- 3.2)% in 2.0 mmol/L TCE treated NHEK with a significant difference (P0.01), but there was no change of Caspase-9 activities. 100 micromol/L Z-LEHD-FMK pretreatment decreased the Caspase-3 activities to (0.338 +/- 0.011) nmol pNA * min(-1) * ml(-1), annexin-V(+)/PI(-) proportion decreased to (16.1 +/- 1.7)% in 2.0 mmol/L TCE treated NHEK. And the Caspase-9 activities decreased from (0.821 +/- 0.031) to (0.240 +/- 0.043) nmol pNA * min(-1) * ml(-1) with a significant difference (P0.01). NHEK was cultured for 4, 8, 12, 24 h after a 4-hour treatment with 2.0 mmol/L TCE. Rhod123 fluorescence intensity (FI) were respectively with a marked decrease as compared with 0 h (18.7 +/- 0.5, all P0.01). At 0.125, 0.5 and 2.0 mmol/L TCE treated NHEK for 4 h then cultured 8 h, Rh123 FI were 16.1 +/- 0.5, 12.1 +/- 0.6 and 8.1 +/- 0.6 with a marked decrease as compared with control (18.1 +/- 0.5, all P0.01).TCE-induced NHEK apoptosis is mediated intrinsically through the mitochondrial pathway of the decrease of DeltaPsim and the Caspase-9 dependent activation of Caspase-3.

We have evaluated the role of circulating serum immunoglobulins (IgG) which inhibit the growth of thyroid in the etiology of thyroid atrophy in endemic cretinism. Twenty nongoitrous cretins (13 women and 7 men, age range: 9-33) were classified on the basis of clinical criteria for cretinism in China. They were born and living in an iodine deficient area, Xinjiang, northwest China. Antimicrosomal antibody titers were negative in all serum. Nine patients (seven women and two men; age range: 11-23) were biologically primary hypothyroid. Seven subjects were of a myxedematous form and two subjects were of a mixed form. We have studied thyroid-growth inhibiting immunoglobulin (TGII) activity that was measured as an inhibitory effect of 4 mg/ml IgG on TSH-induced [3H]-thymidine incorporation into the DNA of a rat thyroid follicular cell line, FRTL5 cells. Six (five women and one man) out of the nine patients with primary hypothyroidism (66.7 percent) had TGII. We also measured other growth-blocking IgG that inhibited [3H]-thymidine incorporation into DNA stimulated by insulin-like growth factor-I (IGF-I), a growth factor working through a cAMP-independent pathway. Five (three women and two men) out of nine patients (55.6 percent) with nongoitrous primary hypothyroidism had IGF-I-blocking IgG. These results indicate that TGII plays an important role in atrophy of the thyroid in spite of increased serum TSH concentrations, and IgG which inhibits thyroid growth stimulated by IGF-I also might play a role in thyroid atrophy in some endemic cretins.(ABSTRACT TRUNCATED AT 250 WORDS)

To explore mechanism of dermal toxicity of trichloroethylene(TCE).Normal human keratinocytes (KC) were isolated from foreskins of healthy donors undergoing circumcision by two-step trypsin digestion and cultured in serum-free medium. Cells were treated with medium, 1% acetone (volume fraction) 0.125, 0.500 or 2.000 mmol/L TCE for different time (4, 8, 12 or 24) hours. After treatment, MTT assay and ATPase activity detected, inhibition ratio of mitochondrial enzyme was calculated according to optical density (A) value of MTT assay. Mitochondrial membrane potential (MMP) was detected by flow cytometry FCM after being stained with Rhodamine123 (Rh123). Morphological changes were also observed through transmission electron microscope (TEM).Cellular viability and ATPase activity declined with dose of TCE, while inhibition ratio of mitochondrial enzyme increased with dose of TCE. FCM results showed that after treatment with 2.000 mmol/L TCE, fluorescence density of Rh123 decreased quickly from 18.73 +/- 0.45(0 h) to 8.20 +/- 0.66(8 h) (P0.01). After 8 h, fluorescence density maintained at the level equal to that of 8 h (fluorescence density of Rh123 were 8.20 +/- 0.36 and 8.20 +/- 0.40 for 12 and 24 h respectively, compared with that for 8 h group, P0.05). The results also showed that MMP diminished with dose of TCE. Under TEM, mitochondria in TCE-treated group appeared extensive swelling and vacuolar degeneration with less matrix and obscure or vanished mitochondria cristae but in control group, mitochondrial structure was integrated, with uniform matrix and visible mitochondria cristae.TCE could inhibit mitochondrial metabolic enzyme, reduce ATP production, diminish MMP, and destroy ultrastructure of mitochondria in KC, all these contributing to the cytotoxicity of TCE.

To investigate the clinical character and surgical management in coexistence of cervical and lumbar spine disease.53 cases with coexistence of cervical and lumbar spine disease were analyzed for clinical character and follow-up outcomes. 19 single cervical operation cases, 16 single lumbar operation cases and 7 combined cervical lumbar operation cases, all patients were recorded with JOA score.The cases with cervical and lumbar intervertebral disc showed at least 2 segments. After 6 months follow-up, 35/44 cases symptom were relieved obviously, of which 24/35 cases were single operation, relief rate is 75.9%, satisfactory rate is 80.0%; of which 11/35 cases were continuous cervical lumbar operation, relief rate is 78.4%, satisfactory rate is 78.5%. 6/44 cases' symptom with only cervical or only lumbar operation were relieved incompletely, 3/44 cases' symptom with second operation relieved incompletely. 5 cases missed diagnosis on the first operation. 29 cases with responsible focus, of which 25 cases were followed up, relieved obviously, relief rate is 76.5%, satisfactory rate is 96.0%.The cases with cervical and lumbar intervertebral disc showed at least 2 segments, the same basis of the spinal canal stenosis and disc herniation is degeneration of spine. certain responsible focus and correct surgical management can get good treatment results.

Hotien county in Xinjiang province, China, is an area of severe iodine deficiency and has a high infantmortality rate. We investigated whether iodine replacement through iodination of the irrigation water would decrease infant mortality.We added potassium iodate to irrigation water over a 2 to 4 week period beginning in 1992 in certain areas of three townships (Tusala, Long Ru, and Bakechi). Logistic regression analysis was used to compare the odds ratios for infant and neonatal mortality in treated and intreated areas.The median urinary iodine concentration significantly increased in women of child-bearing age from10 micrograms/L to 55 micrograms/L. Infant-mortality rates decreased in the treated areas of Long Ru (mean [SD] 58.2 [4.4] per 1000 births to 28.7 [7.1] per 1000 births), Tusala (47.4 [12.4] per 1000 births to 19.1 [1.5] per 1000 births), and Bakechi (106.2 [9.5] per 1000 births to 57.3 [7.3] per 1000 births). Similar results were also seen for neonatal mortality. On regression analysis iodine treatment and time were significant independent predictors of infant mortality.Iodine supplementation of irrigation water in areas of severe iodine deficiency decreases neonatal and infant mortality. Iodine replacement has probably been an important factor in the national decrease in infant mortality in China.Hotien county in Xinjiang province is an area of severe iodine deficiency which also has a high infant mortality rate (IMR). The authors investigated whether iodine replacement through iodination of irrigation water would decrease the level of infant mortality. Potassium iodine was added to irrigation water over a 2-4 week period beginning in 1992 in certain areas of Long Ru, Tusala, and Bakechi. The median urinary iodine concentration significantly increased in women of child-bearing age from less than 10 mg/l to 55 mg/l, while IMR decreased in Long Ru from a mean of 58.2/1000 births to 28.7/1000, in Tusala from 47.4/1000 to 19.1/1000, and in Bakechi from 106.2/1000 to 57.3/1000. Similar results were also observed for neonatal mortality. Iodine treatment and time were significant independent predictors of infant mortality.

To explore the effects of large dose of Astragalus membranaceus (Astragalus) on the dentritic cell (DC) induction in vitro and augumentation by peripheral mononuclear cell (MNC) and on antigen presenting ability of DC in children with acute leukemia.Forty-four children with acute leukemia in complete remission stage were divided into two groups. Twenty patients in the Astragalus (90 g daily) group were treated with large dose of Astragalus (90 g daily) based on conventional chemotherapy for one month, while 24 patients in the control group received chemotherapy alone. MNC were extracted from peripheral blood by wall-sticking method and cultured with such cell factors as interleukin-4, gramulocyte macrophage colony stimulating factor, tumor necrosis factor-alpha for 7-8 days. Phenotype of DC was assayed by flow cytometry and antigen presenting ability of them was assayed by mixed lymphocyte reaction.There was no morphological difference in MNC induced DC between the two groups. The average number of DC in Astragalus group and control group was 4.4 x 10(6) / 2.5 x 10(6) MNC and 2.6 x 10(6) / 2.5 x 10(6) MNC, respectively, showing significant difference (P0.001). DC in Astragalus group could stimulate the proliferation of allogeneic lymphocytes strongly, showing significant difference when compared with that in the control group (P0.001). Conclusion Large dose of Astragalus could increase the DC induction of MNC and enhance the antigen presenting ability of DC in acute leukemia patients.

To investigate the apoptosis-inducing effect of trichloroethylene (TCE) on cultured normal human epidermis keratinocytes (NHEK) in vitro.NR(50) values (the concentration of neutral red absorbed is reduced to 50%) of TCE on NHEK were assayed by neutral red uptake (NRU), and the administered dose of TCE was determined. Lipid peroxidation (LPO) and oxidative stress were assessed by measurement of malondialdehyde (MDA) contens and superoxide dismutase (SOD) activity. Transmission electron microscope (TEM) were used to observe morphologic changes, flow cytometer (FCM) was used to measure DNA contents and calculate cell apoptosis rate and proliferation index (PI).NR(50) values of TCE on NHEK was found to be 4.53 mmol/L (95% CI: 3.92-5.13 mmol/L). The increase in MDA content and inhibition of SOD activity in a concentration-dependent manner were shown after NHEK was treated with a series of dose of TCE 4 h later, and typical morphologic changes of apoptosis were also observed by TEM examination. FCM analysis revealed a sub-G(1) peak in the apoptotic cells. The apoptotic rate in TCE 0.125, 0.500, 2.000 mmol/L exposed groups (31.83%, 38.63%, 44.35%, respectively) were significantly higher than that in blank control (18.42%), while PI in TCE 0.125, 0.500, 2.000 mmol/L group (3.26%, 2.48%, 2.07%, respectively) were significantly lower than that in blank control (4.99%).TCE may induce apoptosis of cultured NHEK in vitro, and inhibit cell proliferation through lipid peroxidation and oxidative stress.

Background Endoplasmic reticulum stress (ER stress) is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone), is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress–induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC) are poorly understood. Methodology/Principal Findings In this study, we investigated the effect of the endoplasmic reticulum (ER) stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM) before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153) in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. Conclusions/Significance Our results demonstrate that Pae reverses ER stress–induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

A series of 4′-(R)-hydroxy-5′-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines were synthesized by the reaction of 3,4-epoxy-5-(S,trans)-dimethoxymethyl-tetrahydrofuran and nucleobases under the catalysis of potassium tert-butoxide and 18-crown-6. Compounds 6a, 6c and 7b have shown significant inhibition on the growth of HL-60 cells. The phosphotriester and phosphodiester of isonucleoside 8a-d were synthesized and cytotoxic activities were reported. The conformation of isonucleosides in solution was studied by 1H NMR.

To explore the effect of diabetic duration and blood glucose level on insulin like growth factor 1 (IGF-1) gene expression and serum IGF-1 level.Diabetes was induced into Sprague Dawley rats by alloxan and then the rats were subdivided into different groups with varying blood glucose level and diabetic duration. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), IGF-1 peptide and serum IGF-1 concentration by enzyme-linked immunosorbent assay (ELISA).During early diabetic stage (week 2), in comparison with normal control group (NC), IGF-1 mRNA (1.17 +/- 0.069 vs 0.79 +/- 0.048, P0.001; 1.17 +/- 0.069 vs 0.53 +/- 0.023, P0.0005, respectively), IGF-1 peptide contents [(196.66 +/- 14.9) ng/mg(-1) vs (128.2 +/- 11.25) ng/mg(-1), P0.0005; (196.66 +/- 14.9) ng/mg(-1) vs (74.43 +/- 5.33) ng/mg(-1), P0.0001, respectively] were reduced in liver tissues of diabetic rats. The IGF-1 gene downregulation varied with glucose control level of the diabetic state, and deteriorated gradually further with duration of diabetes. By month 6, hepatic tissue IGF-1mRNA was 0.71 +/- 0.024 vs 1.12 +/- 0.056, P0.001; 0.47 +/- 0.021 vs 1.12 +/- 0.056, P0.0005, respectively. IGF-1 peptide was (114.35 +/- 8.09) ng/mg(-1) vs (202.05 +/- 15.73) ng/mg(-1), P0.0005; (64.58 +/- 3.89) ng/mg(-1) vs (202.05 +/- 15.73) ng/mg(-1), P0.0001 respectively. Serum IGF-1 was also lowered in diabetic group with poor control of blood glucose. On week 2, serum IGF-1 concentrations were (371.0 +/- 12.5) ng/mg(-1) vs (511.2 +/- 24.7) ng/mg(-1), P0.0005, (223.2 +/- 9.39) ng/mg(-1) vs (511.2 +/- 24.7) ng/mg(-1), P0.0001 respectively. By month 6, (349.6 +/- 18.62) ng/mg(-1) vs (520.7 +/- 26.32) ng/mg(-1), P0.0005, (188.5 +/- 17.35 vs 520.7 +/- 26.32) ng/mg(-1), P0.0001, respectively. Serum IGF-1 peptide change was significantly correlated with that in liver tissue (r=0.99, P0.001). Furthermore, no difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.The influence of diabetic status on IGF-1 gene expression in liver tissues is started from early diabetic stage, causing down regulation of IGF-1 expression, and progresses with the severity and duration of diabetic state. Accordingly serum IGF-1 level decreases. This might indicate that liver tissue IGF-1 gene expression is greatly affected in diabetes, thus contributing to reduction of serum IGF-1 level.