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Xue-Feng Tang,1 Ya Cao,1 Dong-Bin Peng,1 Guo-Sheng Zhao,2 Ying Zeng,1,3 Zi-Ran Gao,1 Yang-Fan Lv,1 Qiao-Nan Guo1 1Department of Pathology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China; 2Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 3Department of Pathology, Daping Hospital, Army Medical University, Chongqing 400037, China Background: Notch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported. Materials and methods: In this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group. Results: Comparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments. Conclusion: Notch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene Hes1 and effector MMP7. Keywords: osteosarcoma, prognosis, metastasis, Notch3, Hes1, MMP7

Metastasis is the leading cause of cancer‑related death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stem‑cell phenotype and anoikis resistance in OS are mostly unknown. Fos‑like antigen 1 (FOSL1) is important in maintaining a stem‑like phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stem‑like properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumor‑sphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stem‑cell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1‑mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumor‑sphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemness‑related factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1‑mediated stem‑like properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem cell‑like phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.

Background: Chronic alcoholic liver disease (CALD) is a global health problem which includes multiple pathological processes such as immune inflammation and oxidative stress. 4-hydroxy-2(3H)-benzoxazolone (HBOA), an alkaloid isolated from Acanthus ilicifolius L, has been shown to exert hepatoprotective and immunomodulatory effects. However, its effects on CALD remain unclear. This study aimed to investigate the effects and underlying mechanisms of HBOA on CALD., Methods: Rats were administered alcohol by gavage continuously for 12 weeks to establish the CALD model, and then treated with HBOA by gavage for 4 weeks. Transcriptomics and metabolomics were used to predict the potential mechanisms of the effects of HBOA on CALD. Liver histology and function, oxidative stress, inflammatory cytokines, and the TLR4/NF-κB pathway components were evaluated., Results: HBOA significantly improved alcohol-induced liver injury and steatosis. It decreased the expression levels of pro-inflammatory cytokines (tumour necrosis factor-α [TNF-α], interleukin (IL)-1β, and IL-6), and increased the activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione [GSH], and glutathione peroxidase [GSH-Px]). Western blotting confirmed that HBOA treatment largely diminished NF-κBp65 nuclear translocation. Comprehensive transcriptomics and metabolomics analyses indicated that HBOA regulated the glycerophospholipid metabolism pathway to achieve therapeutic effects in rats with CALD., Conclusion: HBOA has a therapeutic effect on rats with CALD. Its mechanism of action mainly affects the glycerophospholipid metabolic pathway to promote lipid metabolism homeostasis by regulating the expression of Etnppl , Gpcpd1, and Pla2g4c . In addition, it may also inhibit the TLR4/NF-κB signaling pathway, thereby reducing the immune-inflammatory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Xing, Wei, Yang, Zhao, Ma, Sun, Guo, Su, Fang, Lin, Liu and Zhu.)

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that a reevaluation of current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective and safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis therapy, metabolic targets therapy, and nanomedicine therapy. The tumorigenesis and development of osteosarcoma is closely related to angiogenesis. Thus, anti-angiogenesis therapy is crucial to treat osteosarcoma; however, recent clinical trials found that it has insufficient efficacy. To solve this problem, the causes of treatment failure and improve treatment strategies should be investigated. This review focuses on summarizing the pathophysiological mechanisms of angiogenesis in osteosarcoma and recent advances in anti-angiogenesis treatment of osteosarcoma. We also discuss some clinical studies, with the aim of providing new ideas to improve treatment strategies for osteosarcoma and the prognosis of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Xia, Wang, Wang, Bao and Zhao.)

Small intestinal lipomatosis is a rare condition that presents a diagnostic challenge due to the absence of identifiable clinical symptoms and limitations of small intestine examination methods. Consequently, preoperative diagnosis is difficult and only a limited number of cases have been documented in the scientific literature. Here, we report a rare case of volvulus caused by small intestinal lipomatosis. A 58-year-old female patient was tentatively diagnosed with acute ileus. The whirl sign was detected using abdominal three-dimensional enhanced computed tomography, along with marked local intestinal dilation and multiple irregular fat-like containing lesions. During surgery, abnormal dilation of the small intestine between 80 and 220 cm from the ileocecal valve was detected and the affected intestine displayed a folded and twisted configuration. Examination of the resected intestine showed that the inner wall of the diseased intestinal lumen was covered with more than 100 lipomas of different sizes, the largest of which measured ~8.0 cm in diameter. Based on clinical symptoms alone, it was difficult to identify the cause of intestinal volvulus before surgery. Complete resection of the affected small intestine and subsequent pathological analysis yielded a definitive diagnosis of small intestinal lipomatosis. While small intestinal lipomatosis is a rare condition, prognosis is favorable if diagnosed early and treated appropriately. The application of three-dimensional enhanced computed tomography imaging can aid in accurate diagnosis, while complete resection of the affected small intestine is crucial to improve patient prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, Zhao, Wang, Jiang, Liu, Li and Zhao.)

Background: Accurately predicting the risk of lower extremity (LE) radiating pain after surgery is an important endeavor for spinal surgeons. Our study aimed to identify risk factors for LE radiating pain after decompression with full-endoscopic lumbar discectomy (FELD) and develop a nomogram., Methods: We retrospectively reviewed the medical data of patients with lumbar disc herniation who underwent FELD. Two hundred thirty-five patients diagnosed at our hospital from January 2015 to December 2020 were used for model development. The independent risk factors for LE radiating pain after surgery were determined by least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis. A nomogram was developed to predict the risk of LE radiating pain based on independent risk factors. Receiver operating characteristic curve, calibration curve, and decision curve analyses were used to evaluate the predictive performance. The nomogram was further verified by an independent cohort., Results: Three hundred seventy-five patients were enrolled in this study, with 102 patients in the training cohort reporting LE radiating pain after FELD, while 133 patients did not. In the validation cohort, 57 patients reported LE radiating pain after FELD, while 83 patients did not. The model was established by multivariate logistic regression analysis. The risk factors included a higher Michigan State University classification of herniated discs, increased disease course, increased time of surgery, reduced lateral recess width, and an interlaminar surgical approach, compared to transforaminal approach. The C-indices and the area under the receiver operating characteristic curve of the predictive model demonstrated good discrimination. Good predictive performance and accuracy were also observed in the validation cohort., Conclusions: A novel nomogram for predicting recurrent LE radiating pain within 1 week after FELD was established and validated. More aggressive pain management strategies should be considered for patients at high risk of LE radiating pain after surgery, as predicted by this model., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study aims to evaluate the efficacy and safety of the full-endoscopic lumbar discectomy (FELD) via lateral superior articular process (LSAP) approach and full-endoscopic transforaminal discectomy (FETD) for treating far lateral lumbar disk herniation (FFLDH)., Methods: From January 2020 to June 2022, patients who were diagnosed as FLLDH underwent the FELD via LSAP approach or FETD. The operation time, estimated blood loss, length of hospital stays, and complications were recorded. The visual analog scale (VAS) for back pain, VAS for leg pain, and the Oswestry Disability Index (ODI) scores was measured during preoperative and postoperative follow-up., Results: Thirty-two patients were enrolled in this study, of which 12 patients were treated with the FELD via LSAP approach (LSAP-FELD group) and 20 patients underwent FETD (FETD group). The LSAP-FELD group exhibited significantly shorter operation times and hospital stays compared to the FETD group, while no statistically significant differences were observed in intraoperative blood loss and complication rates. There were no significant differences in the VAS for back pain, the VAS for leg pain, and the ODI score between the two groups preoperatively and three days, three months, and the last follow-up postoperatively., Conclusions: Both the FELD via LSAP approach and FETD have demonstrated favourable clinical efficacy in the treatment of FLLDH. Notably, the FELD via LSAP approach shows the advantages of shorter operation time and hospital stays., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples., (© 2023. Springer Nature Limited.)

Background: The purpose of this study was to observe the safety and efficacy of CalliSpheres microspheres drug-eluting beads (DEB) transhepatic arterial chemoembolization (CSM-TACE) for liver metastasis of gastric cancer (GCLM) combined with trans-arterial infusion therapy (TAIT) as the primary focus of gastric cancer., Research Design and Methods: Unresectable advanced GCLM patients were collected for retrospective analysis. Patients who progressed after chemotherapy or could not receive systematic chemotherapy were selected. CSM-TACE was used for GCLM treatment and oxaliplatin for TAIT of primary focus of gastric cancer. Adverse reactions, tumor reactions, survival rate, and survival time during treatment were recorded, and prognostic factors were analyzed., Results: Forty-three patients from four oncology centers met inclusion criteria and were enrolled. CSM-TACE averaged (1.51 ± 0.51) times and TAIT averaged (4.58 ± 1.65) times. The follow-up time was 2.5-49 months, and the 6-month, 1-year, and 2-year survival rates were 86.0%, 72.1%, and 41.9%, respectively, with a median overall survival of 11.5 months. The adverse reactions during treatment were grade 1-3. The hazard ratio (HR) of combination therapy was 0.51 ( P  = 0.040), and the HR of TAIT frequency was 0.34 ( P  = 0.002), which were independent protective factors affecting prognosis., Conclusions: CSM-TAC for GCLM combined with TAIT for primary focus of gastric cancer is safe and efficacious, which is worthy of clinical promotion and application.

Objective: This study aimed to prospectively observe the efficacy and safety of CalliSpheres drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for refractory non-small-cell lung cancer (NSCLC)., Methods: The interventional therapy plan was as follows: 300-500 μm CalliSpheres drug-loaded microspheres were loaded with epirubicin, and then slow embolization of tumor supplying artery was performed after microcatheter superselection. Chest enhanced computed tomography and related hematological examination were reviewed after 2 months of DEB-BACE, and the tumor response after the first interventional therapy was evaluated using modified response evaluation criteria in solid tumors. The overall survival (OS) of patients was determined, and the quality of life and the incidence rate of adverse reactions were observed., Results: From January 2019 to January 2021, 43 patients with refractory NSCLC were enrolled. The patients were followed up until June 2022. All 43 patients underwent DEB-BACE 1.79 ± 0.69 times on average. The 3-, 6-, 12-, and 24-month survival rates were 100%, 86.0%, 41.9%, and 11.8%, respectively. The median OS was 11.5 months. After the first interventional treatment, cough and wheezing significantly improved in 31 patients, hemoptysis was effectively controlled in 12 patients, and superior vena cava compression disappeared in 2 patients after 2 times of treatment. The general health status of the patients after treatment significantly improved compared with that before treatment, including the improvement in physical and emotional functions. Fatigue, nausea and vomiting, dyspnea, and insomnia improved significantly after treatment. No serious adverse events, such as spinal cord injury and cerebral embolism, were observed during the perioperative period. The main adverse reaction after DEB-BACE was chest pain (13/43, grade 1) followed by fever (10/43, grade 1-2), which was significantly relieved within 3-5 days after symptomatic treatment. Other adverse reactions included irritating cough, nausea and vomiting, and bone marrow suppression, and the incidence was less than 20%., Conclusions: DEB-BACE was effective and safe in treating refractory NSCLC, which could significantly improve patients' quality of life and was worthy of clinical promotion and application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Liu, Qin, Sun, Su, Yu, Zhou, Gao, Wang, Zhao and Zhao.)

Objectives: To develop a rapid test for salivary bacterial community based on direct PCR (dPCR) and high resolution melting (HRM) curve analysis, to evaluate its application value in forensic medicine., Methods: The salivary bacteria were collected by centrifugation and then resuspended in Tris-EDTA (TE) buffer, and directly used as the template for amplification and HRM curve analysis (dPCR-HRM) of the 16S rDNA V4 region. The genotype confidence percentage (GCP) of the HRM profiles compared with the reference profile was calculated. The template DNA was extracted by traditional kit and then PCR-HRM (namely kPCR-HRM) was used as reference to validate the feasibility of dPCR-HRM. The gradient dilution templates, population samples and simulated salivary stains were analyzed by dPCR-HRM to evaluate its sensitivity, typing ability and adaptability., Results: Using dPCR-HRM method, the HRM profiles of salivary bacterial community were obtained within 90 minutes. The GCP between dPCR-HRM and kPCR-HRM was greater than 95.85%. For general individuals, the HRM type of bacterial community could be determined with 0.29 nL saliva by dPCR-HRM. The 61 saliva samples could be divided into 10 types. The typing of salivary stains deposited within 8 h was the same as those of fresh saliva (GCP>90.83%)., Conclusions: dPCR-HRM technology can be used for rapid typing of salivary bacterial community, and has the advantage of low cost and simple operation.

Background: Primary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres ® microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres ® for hepatocellular carcinoma (HCC) with hypersplenism., Methods: Ninety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed., Results: Before CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P<0.05). There were no significant differences in RBC before and after treatment (P > 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P<0.05). However, the level of CHE returned to the preoperative level 1 month after CSM-TACE in the CSM-TACE group. The objective response rate (ORR) and median overall survival (OS) in the CSM-TACE+PSE group were higher than those in the CSM-TACE group (P<0.05). The adverse reactions of the two groups were fever, abdominal pain, stomach discomfort, nausea, and vomiting, and no serious complications occurred. The degree of abdominal pain and fever in the experimental group was lower than that in the control group (P > 0.05)., Conclusions: Simultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Feng, Liu, Li, Liu, Gao, Shen, Zhang, Zhao and Zhang.)

Objective: To observe the early changes in peripheral blood cytokine levels after treatment of metastatic hepatic carcinoma (MHC) with CalliSpheres microspheres drug-eluting beads (DEB) transcatheter arterial chemoembolization (CSM-TACE)., Methods: Twenty-eight patients with refractory MHC who underwent CSM-TACE were selected prospectively, and 5mL of peripheral blood was collected before CSM-TACE and on the 2nd and 5th day after CSM-TACE. Flow cytometry was used to detect immunological indicators. The early changes in levels of peripheral blood cell inflammatory factors Th1 (interleukin 2 (IL-2), tumor necrosis factor-α (TNF-a), interferon (IFN-r)), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were observed after CSM-TACE, as well as the ratio of CD4 + /CD8 + ., Results: All the 28 patients underwent CSM-TACE successfully. CT at 4 days after CSM-TACE showed clear outline low-density changes in liver tumors, and honeycomb necrosis was observed in the tumors in some cases. After CSM-TACE, the IL-6 and IL-10 levels were increased and then decreased again. After CSM-TACE, IL-2 showed a trend of transient increase and then decreased again, and the TNF-a level decreased temporarily, and then decreased. After CSM-TACE, the IFN-r level showed a continuous and slowly increasing trend. The IL-17 level showed a continuous downward trend, and the CD4 + /CD8 + ratio showed a gradual and continuous upward trend, and there was a negative correlation between them., Conclusions: There are complex dynamic changes in TH1/Th2 in the early stage of CSM-TACE, and the acute inflammatory response and the enhancement of the body's immune anti-tumor response coexist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Liu, Zhao, Li, Gao, Ren, Bian, Wu and Zhang.)

Objective: To explore the clinical efficacy and prognostic factors of the use of Gelfoam for drug-eluting bead (DEB) transarterial chemoembolization (GMD-TACE) in patients with unresectable large hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT)., Methods: A retrospective analysis was conducted using the mRECIST standard to evaluate tumor response after GMD-TACE. Overall survival time, median survival time, time to progression (TTP) after the first intervention, and other treatment methods were recorded., Results: The follow-up time was 2-110 months (mean 17.97 + 19.12 months), the median follow-up time was 12.5 months, and the first TTP after the first GMD-TACE was 4 months (95% CI 3.020-4.980). The median overall survival (OS) time was 14 months (95% CI 9.801-18.199). The 1-, 3-, and 5-year survival rates were 53.6%, 32.3%, and 8.9%, respectively. Multivariate analysis showed that the type of tumor thrombus was an independent factors affecting prognosis, and combination therapy was a protective factor affecting prognosis., Conclusions: GMD-TACE can be used as the core treatment for unresectable large HCC combined with a PVTT. This can improve the quality of life and further improve the median OS, and is worthy of clinical promotion and application.

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125 I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125 I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125 I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125 I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125 I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS., (© 2022. The Author(s).)

Abstract: To assess the clinical efficacy and safety of gelatin sponge microparticles-transcatheter arterial chemoembolization (GSMs-TACE) plus synchronous antigen-presenting dendritic cell (DC) sequential reinfusion for advanced large liver cancer (LC).Patients with large LC were assigned to the experimental (combined sequential DC therapy) or control group. All patients received standardized GSMs-TACE. In the experimental group, 60 mL of peripheral blood was collected for in vitro culture of DCs (10-14 days). Then, intravenous reinfusion was conducted 3 times within 10, 20, and 30 days after surgery. Adverse reactions during the treatment were recorded and evaluated. The overall survival, transcatheter arterial chemoembolization frequency, and physical score (PS) were calculated.The median survival time of the experimental group was significantly longer than that of the control group. There were significant differences in median progression-free survival between the 2 groups (P < .05) and the objective effective rate at 1 and 6 months and 1 year (P < .05), but not 2 years (P > .05). The PSs of 2 groups were significantly improved at 1 month after GSMs-TACE, with more obvious improvement in the experimental group (P < .05).GSMs-TACE plus synchronous DC sequential reinfusion significantly prolonged the median survival time, improved the tumor response rate and PS, prolonged progression-free survival, and reduced intervention frequency. GSMs-TACE plus synchronous DC sequential reinfusion treatment is suitable for comprehensive treatment of patients with advanced larger LC in China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients., Methods: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively., Results: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups., Conclusion: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.

Objective: To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM)., Methods: Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed., Results: By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant., Conclusions: The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application., (© 2021. The Author(s).)

Objective: To retrospectively analyze the clinical efficacy of external fixation in the treatment of femoral neck fracture with two different pin layout., Methods: From April 2000 to April 2018, 140 cases of femoral neck fracture were treated with closed reduction and percutaneous pin external fixation, among them 121 cases were followed up for more than 1 year, including 31 cases in traditional group, 12 males and 19 females, aged 45 to 74(65.4±8.4) years;90 cases in modified group, 39 males and 51 females, aged 12 to 75 (64.5±7.8) years. In traditional group, the first needle was put on the femoral talus, the second and third needles were put under the tension line, and the three needles were not on the same line in the lateral phase; in modified group, the first needle was drilled into the lateralcortex of the femur, obliquely penetrating the distal and proximal end of the femoral talus fracture, and the other two needles were drilled into the medial cortex of the femoral neck and the femoral talus, respectively. The operation time, hospital stay, postoperative ambulation time, femoral neck shortening rate, fracture healing time, fracture healing rate and femoral head necrosis rate of the two groups were observed and compared. Harris hip function score was used one year after operation., Results: These 121 patients were followed-up, the follow up time of traditional group was 13 to 45(30.5±11.4) months;the follow-up time of modified group was 14 to 120(34.5±12.5) months. There was no significant difference in operation time, hospital stay and femoral head necrosis rate between two groups ( P >0.05). There were significant differences between two groups in the time of going to the ground, shortening rate of femoral neck, fracture healing time, fracture healing rate and Harris functional score of the hip 1 year after operation ( P <0.05)., Conclusion: Compared with the traditional group, the modified group has the advantages of lower femoral neck shortening rate, shorter fracture healing time, higher fracture healing rate and higher Harris hip function score.

Background: To observe the medium- and long-term clinical efficacy and safety of radioactive 125 I seed implantation for refractory malignant tumours based on CT-guided 3D template-assisted technique., Methods: Twenty-five patients with refractory malignant tumours who underwent radioactive 125 I seed implantation based on CT-guided 3D template-assisted technique were selected. The post-operative adverse reactions were recorded. The number of puncture needles and particles used in the operation, dosimetric parameters, post-operative physical strength scores, and tumour response were statistically analysed. The overall survival time and survival rate were calculated, and the effect and prognosis were assessed., Results: 125 I seed implantation was successful in all patients without serious complications. The average number of implanted puncture needles was 17 (19.12 ± 13.00), and the median number of particles was 52 (55.12 ± 32.97). D 90 in the post-operative clinical target volume (CTV) (93.24 ± 15.70 Gy) was slightly lower than that in the pre-operative CTV (93.92 ± 17.60 Gy; P > 0.05). The D 90 in the post-operative planning target volume (PTV) (142.16 ± 22.25 Gy) was lower than the pre-operative PTV (145.32 ± 23.48 Gy; P > 0.05). The tumour responses at 6 months post-operatively: complete remission (CR), 20% (5/25); partial remission (PR), 48% (12/25); stable disease (SD), 24% (6/25); progressive disease (PD), 8% (2/25); CR + PR, 68% (17/25); and local control rate, 92% (23/25). The 6-, 12-, and 24-month survival rates were 100, 88, and 52%, respectively. The post-operative physical strength score (Karnofsky performance score, KPS) exhibited a gradual trend towards recovery, which rose to the highest value 12 months after implantation and then decreased slightly, but the average score was still > 90 points. There was one intra-operative pneumothorax, and two patients with superficial malignant tumours developed skin ulcerations. Multivariate analysis of prognosis showed that tumour sites and types were independent risk factors affecting survival. The number of needles and particles and template types were not the factors., Conclusions: 3D template combined with CT-guided radioactive 125 I seed implantation can improve the rational distribution of radiation dose in the tumour target area because accurate radioactive 125 I particle implantation was achieved. This technique has fewer complications and can further extend the overall survival and improve the quality of life., Trial Registration: Registration number: ChiCTR2000034566 2020/7/10 0:00:00 Retrospectively registered.

Metastasis is the primary cause of high mortality in patients with osteosarcoma (OS). However, the molecular mechanisms underlying the regulation of metastatic disease are yet to be determined. Differentially expressed in FDCP 6 homolog (DEF6) has been demonstrated to be correlated with the metastatic behavior of several cancers, such as breast, ovarian and colorectal cancers. However, the role of DEF6 in OS remains unknown. Accordingly, the current study aimed to investigate the relationship between DEF6 expression and the malignant behavior of OS. The results revealed that high levels of DEF6 in OS tissues were associated with advanced clinical stage and metastases. Furthermore, immunohistochemistry results predicted a poor prognosis in 58 human OS specimens. Additionally, DEF6 expression was reported to be upregulated in human OS cell lines compared with a normal osteoblast cell line. small interfering RNA transfection, cell proliferation and colony formation assays, wound healing assays and Transwell assays were performed. DEF6 was not identified to be a major driver of OS cell proliferation, but it significantly contributed to metastatic potential in vitro . In addition, bioinformatics, western blotting and immunohistochemistry results indicated that MMP9 expression was positively correlated with DEF6 expression in human OS. To summarize, the results revealed that increased levels of DEF6 were associated with metastasis and poor prognosis in human OS and that DEF6 expression is positively correlated with MMP9 expression. The results indicated that DEF6 may serve as a potential antimetastatic target for OS., (Copyright: © Zhang et al.)

Background: Very few studies have been published on the hemodynamic changes associated with spinal anesthesia induced with ropivacaine during cesarean deliveries in preeclamptic women., Aim: To record and analyze hemodynamic data in women with preeclampsia undergoing cesarean delivery after spinal anesthesia induced with ropivacaine., Methods: Ten eligible women with preeclampsia were enrolled in this prospective observational study. Spinal anesthesia was performed with 2.4 mL of 0.5% ropivacaine. Hemodynamic changes were then analyzed at multiple time points. The hemodynamic responses to vasopressor interventions and uterotonic agents, as well as maternal and neonatal outcomes were also recorded., Results: Stable hemodynamic trends were observed in this study. Cardiac output (CO) and stroke volume increased mildly during surgery. In contrast, mean arterial pressure and systemic vascular resistance showed a moderate decrease from induction until the end of surgery. Central venous pressure dramatically increased after delivery. Oxytocin administration was associated with the most significant hemodynamic fluctuations during surgery, namely, an increase in CO and heart rate. Phenylephrine intervention was only required in three patients, and caused an increase in mean arterial pressure and systemic vascular resistance along with a decrease in heart rate, stroke volume, and CO. No maternal and neonatal complications were observed during this study, except transient episodes of hypotension., Conclusion: Spinal anesthesia for caesarian delivery with ropivacaine in women with preeclampsia is linked to modest hemodynamic changes of no clinical significance in this study. Careful cardiovascular monitoring is still recommended, particularly after the delivery of the fetus or the use of oxytocin., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The incidence of acute myeloid leukemia (AML) increases with age. The overall prognosis remains poor for older patients. Studies on the efficacy of decitabine, an epigenetic agent, in older patients with AML have reported conflicting results., Materials and Methods: For this meta-analysis, we performed a literature search and collected 38 studies (including 3298 patients with AML) to evaluate the role of decitabine in elderly patients with AML. We used complete response (CR) or overall response (OR) rate as indicators of effectiveness., Results: Patients treated with decitabine have a higher CR/OR rate than those treated with low-dose cytarabine (CR, 2.60; 95% confidence interval [CI], 1.64-4.14; OR, 4.88; 95% CI, 1.98-12.04) or CAG/HAG (low-dose epirubicin and cytarabine with granulocyte stimulating factor/low-dose homoharringtonine and cytarabine with granulocyte stimulating factor) regimens (CR, 2.53; 95% CI, 1.98-3.23; OR, 2.89; 95% CI, 2.24-3.73). However, patients treated with decitabine had a CR rate equivalent to those treated with intensive chemotherapy (CR, 0.58; 95% CI, 0.28-1.22; P = .15). Use of decitabine in combination with other regimens resulted in a higher CR/OR rate than did use of decitabine alone (P < .001); there was no significant difference in infection rates and early death rates (P > .05)., Conclusion: The findings presented in this article show that decitabine is effective and safe for the treatment of older patients with AML., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma., Competing Interests: None.

Tumor cells must resist anoikis to metastasize. There is a key role of angiogenesis in the growth and metastasis of tumors. However, the relationship between anoikis resistance and angiogenesis has not been well explored in human osteosarcoma. In the present study, we reported the higher expression of vascular endothelial growth factor‑A (VEGF‑A) in osteosarcoma cells that were resistant to anoikis than in parental osteosarcoma cells, promoting the proliferation, tube formation, and migration of human umbilical vein endothelial cells (HUVECs). Src, JNK (Jun amino‑terminal kinase) and ERK (extracellular signal‑regulated kinase) signaling pathway phosphorylation was activated in anoikis‑resistant cells; Src inhibitor reduced the expression of VEGF‑A and angiogenesis and inhibited JNK and ERK pathway activity. Overexpression of phosphorylated (p)‑Src and VEGF‑A was positively correlated to the metastatic potential in human osteosarcoma tissues, as quantified by immunohistochemistry. In addition, p‑Src expression was directly correlated with VEGF‑A expression and microvessel density in vivo. Our findings revealed that anoikis resistance in osteosarcoma cells increased the expression of VEGF‑A and angiogenesis through the Src/JNK/ERK signaling pathways. Thus, Src may be a potential therapeutic alternative in osteosarcoma angiogenesis and metastasis.

Background: Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear., Methods: We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing., Results: We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models., Conclusions: Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

Background: The association between the tumor necrosis factor-alpha gene (TNF-a) -238G/A polymorphism and the breast cancer has been analyzed in several studies, but the results have been inconclusive. We then performed a meta-analysis to get a precise estimation of the association., Methods: Eight case-control studies with a total of 37,257 cases and 39,564 controls were identified by searching the ISI Web of Knowledge database and the PubMed database up to August 2014., Results: Overall, no association was found between TNF-alpha-238G/A polymorphism and breast cancer in any of genetic model (additive model OR = 1.06, 95%CI: 0.94-1.21, Pheterogeneity = .02; homozygous model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98; dominant model OR = 1.06, 95%CI: 0.92-1.21, Pheterogeneity = .01; recessive model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98). Furthermore, no significant association was identified when stratified by ethnicity (Caucasian, Asian)., Conclusion: This meta-analysis indicated that the TNF-alpha-238G/A polymorphism is not associated with breast cancer risk in the overall population.

To evaluate the safety and efficacy of transarterial arterial chemoembolization (TACE) with gelatin sponge particles (GSPs-TACE) and Huaier granule to treat primary hepatic carcinoma (PHC).A series of 62 patients with PHC were included between June 2009 and December 2011, and randomly assigned to a control (n = 31) or an experimental group (n = 31). The control patients received TACE with 350 to 560 μm GSPs plus lobaplatin chemotherapy. Patients in the experimental group received TACE plus Huaier granule. Treatment safety and mid-to-long-term efficacy were evaluated.Follow-up ranged from 12 to 24 months with a mean of 28.7 months. The 6- and 12-month overall survivals were 100% and 93.5% in the experimental group and 90.3% and 80.6% in control group, respectively. The difference in overall survival at 12 months was significant (χ = 5.213, P < .05), but the difference in median survival in the experimental group (20.6 months) and control group (17.1 months) patients was not significant (χ = 0.745, P > .05). The number of TACE procedures in the experimental group (2.9 ± 8.7) and control group (4.1 ± 7.3) patients was significantly different (χ = 7.262, P < .05). The 6-month (87.1% vs. 73.3%, χ = 5.945) and 12-month (72.4% vs. 64.3%, χ = 6.384) tumor objective response rates in the experimental and control groups were significantly different (P < .05). There were no statistically significant differences in the occurrence of treatment-related adverse reactions in the 2 groups.Transarterial chemoembolization with GSPs and Huaier granule was safe and effective for treating PHC patients.

To retrospectively analyze the safety and efficacy of 350-560 μm gelatin sponge particles combined with single-chemotherapy drug transcatheter arterial chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma without surgical resection.Thirty elderly hepatocellular carcinoma patients without surgical resection, who received Gs-TACE in our hospital, were selected. Slowly injected gelatin sponge particles (350-560 μm)+ 10 mg lobaplatin injection into the regional embolization tumor target vessel. The Response Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response after intervention surgery.Eighty-nine times of intervention TACE were conducted on the 30 patients. The average size of tumor was 8.3 cm. The median survival time was 28 months, and the 1 and 2-year survival rates were 89% and 58%, respectively. The Response Evaluation Criteria for Solid Tumors was used to evaluate the tumor response, and found that the complete response, partial response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after intervention surgery. The patients were divided into groups: 60 to 65 years age group (A), >65 to 75 years age group (B), and >75 years age group (C); the median survival times were 16, 32, and 33 months, respectively, and there was statistical difference between A group, B group, and C group. The analysis of prognosis factors showed that there was statistical significance in age, Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal protein (AFP), and age was the protective factor.Gelatin sponge particles (350-560 μm), combined with transcatheter arterial chemoembolization, provide an alternative method for the treatment of elderly hepatocellular carcinoma without surgical resection.

Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are the most commonly used procedures in cervical spondylosis. However, only a few published studies exist in the literature comparing these two operation types, particularly its mid-term efficacy and safety. Furthermore, in those studies, even large sample trials, when compared, have elicited controversial results, making it inconvenient for clinicians to refer to them. The aim of the present study was to clarify the advantages and shortcomings of the two procedures. Articles indexed in the PubMed, Web of Science, Cochrane Library, EMBASE, China Biological Medicine and China National Knowledge Infrastructure (CNKI) databases, as of March 2016, that met our criteria were searched. A total of 18 trials involving 3,040 patients were included in our final analysis. The most important results drawn from the present analysis were as follows: Insignificant differences were identified in the blood loss [weighted mean difference (WMD)=6.23; 95% confidence intervals (CI), -0.85 to 13.32; P=0.08], surgical time [standardized mean difference (SMD)=0.40; 95% CI, -0.01 to 0.82; P=0.06], the time of hospital stay (SMD=0.05; 95% CI, -0.28 to 0.37; P=0.77) and the total complications rate [odds ratio (OR)=0.86; 95% CI, 0.66 to 1.131; P=0.28] on a comparison of the two operation methods. By contrast, comparing CDA with ACDF, the CDA had higher Short Form survey (SF-36) scores (WMD=1.65; 95% CI, 0.61 to 2.69; P=0.002), a larger range of motion in the operation level (SMD=6.53; 95% CI, 3.89 to 9.17; P<0.0001), a higher rate of neurological improvement following the operation (OR=1.80; 95% CI, 1.29 to 2.52; P=0.0006), a lower Visual Analog Scale (VAS) score of neck pain (WMD= 0.16; 95% CI, -0.28 to 0.05; P=0.006) and arm pain (WMD= 0.12; 95% CI, -0.24 to -0.01; P=0.04). In addition, in the mid-term following the surgery, CDA had a lower Neck Disability Index (NDI; SMD=0.18; 95% CI, -0.28 to -0.07; P=0.001) and a lower reoperation rate of adjacent levels (OR=0.54; 95% CI, 0.35 to 0.85; P=0.007) compared with ACDF. Taken together, these results suggested that CDA and ACDF are efficient and safe methods for dealing with cervical spondylosis. However, with respect to certain specific indicators, such as the reoperation rate of adjacent levels following surgery, the former has several advantages.

Objective: To explore whether T lymphocytes subgroup, B lymphocytes, platelet antigen CD41a, CD61 or platelet antibodies are involved in the platelet transfusion refractoriness., Methods: Forty-seven patients diagnosed as platelet transfusion refractoriness and 32 patients that achieved effective platelet therapy were ennolled in this study. Flow cytometry was performed to detect the proportion of cytotoxic T cell (CD3(+)CD4(-)CD8(+)), helper T cell (CD3(+)CD4(+)CD8(-)) and B lymphocytes (CD19 (+) ), and the expression of platelet glycoproteins, including CD41a and CD61, while platelet antibodies were also measured by solid-phase agglutination., Results: The significant lower level of helper T cell (36.60% vs 48.53%), higher level of cytotoxic T cell (53.26% vs 44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in platelet refractoriness group when compared with effective platelet therapy group (P<0.05). However, the significant difference was not observed in B lymphocytes between the two group (3.02% vs 2.85%, P>0.05). Platelet glycoproteins CD41a and CD61 and antibodies were both expressed at high levels in platelet refractoriness group (88.10% vs 51.69%, 88.36% vs 51.83%, 85.37% vs 14.82%, respectively, P<0.05)., Conclusions: Activation of cytotoxic T cells, suppression of helper T cells, higher expression level of platelet glycoproteins CD41a and CD61 as well as the development of anti-platelet antibodies are involved in the immunologic mechanism of platelet refractoriness.

In this paper, the dynamics of ecosystem macrostructure, qualities and core services during 2000 and 2010 were analyzed for the key ecological function zones of China, which were classified into four types of water conservation, soil conservation, wind prevention and sand fixation, and biodiversity maintenance. In the water conservation ecological function zones, the areas of forest and grassland ecosystems were decreased whereas water bodies and wetland were increased in the past 11 years, and the water conservation volume of forest, grassland and wetland ecosystems increased by 2.9%. This region needs to reverse the decreasing trends of forest and grassland ecosystems. In the soil conservation ecological function zones, the area of farmland ecosystem was decreased, and the areas of forest, grassland, water bodies and wetland ecosystems were increased. The total amount of the soil erosion was reduced by 28.2%, however, the soil conservation amount of ecosystems increased by 38.1%. In the wind prevention and sand fixation ecological function zones, the areas of grassland, water bodies and wetland ecosystems were decreased, but forest and farmland ecosystems were increased. The unit amount of the soil. wind erosion was reduced and the sand fixation amount of ecosystems increased lightly. In this kind of region that is located in arid and semiarid areas, ecological conservation needs to reduce farmland area and give priority to the protection of the original ecological system. In the biodiversity maintenance ecological function zones, the areas of grassland and desert ecosystems were decreased and other types were increased. The human disturbances showed a weakly upward trend and needs to be reduced. The key ecological function zones should be aimed at the core services and the protecting objects, to assess quantitatively on the effectiveness of ecosystem conservation and improvement.

The aim of the study was to explore the clinical outcome of posterolateral and anteromedial approaches in treatment of terrible triad of the elbow. The study involved 12 patients with closed terrible triad of the elbow treated by posterolateral and anteromedial approaches between January 2010 and June 2012. The mechanism of injury included fall from height in 9 patients and traffic accident in 3. According to O'Driscoll classification for fractures of the ulnar coronoid, there were 11 patients with type Ⅰ and 1 with type Ⅱ fractures. According to Mason classification for fractures of the radial head, there were 3 patients with type Ⅰ, 7 with type Ⅱ and 2 with type Ⅲ fractures. All patients were followed up for 12-27 months (average 15.5 months), which showed no pain or severe pain in all patients except for 2 patients with mild pain. At the last follow-up, the mean flexion was for 125°(range, 90°-140°), the mean extension loss for 20°(range, 0°-70°), the mean pronation for 66°(range, 20°-85°) and the mean supination for 60°(range, 30°-85°). The bony union time was 8-14 weeks (average 11 weeks) and the elbows were stable in flexion-extension and varus-valgus in all patients. The elbows maintained a concentric reduction of both the ulnotrochlear and the radiocapitellar articulation. Mild heterotopic ossification of the elbow occurred in 3 patients at 6 months after operation and mild degenerative change in 1 patient at 18 months after operation. The Broberg and Morrey elbow performance score was 82 points (range, 58-98 points). The results were excellent in 6 patients, good in 4, fair in 1 and poor in 1, with excellence rate of 83.3%. The results showed that the combined posterolateral and anteromedial approaches can facilitate the reduction and fixation of terrible triad of the elbow. Repair of radial head, coronoid, medial and lateral collateral ligaments can sufficiently restore the elbow stability, allow early postoperative motion and enhance the functional recovery.

Objectives: The aim of this study was to evaluate the clinical efficacy of simple decompression (SD) versus anterior transposition (AT) of the ulnar nerve for the treatment of cubital tunnel syndrome., Methods: Seven public databases (PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google scholar) were searched from 1971 to December 2013. The overall odds ratios (OR) and their 95% confidence intervals (CI) were pooled to compare the clinical outcomes. Subgroup analysis was performed based on the region, study type, Jadad score, type of AT, and follow-up duration. Meta-analysis was conducted by using Rev. Man 5.1 and Stata 11.0 software., Results: Finally, we included 13 studies involved 1009 (500 patients receiving SD and 509 patients receiving AT) patients with cubital tunnel syndrome. The overall estimate (OR=0.91, 95% CI=0.67-1.23, P=0.536) indicated that there was no significantly statistical difference between the clinical outcomes of patients treated with SD and AT. Meanwhile, subgroup analyses by region, study type, Jadad score, type of AT and follow-up duration showed the consistent results with the overall estimate. In addition, we found that the incidence of complications in patients treated by SD was significantly lower than that in patients treated by AT (OR=0.32, 95% CI=0.17-0.60, P=0.05)., Conclusions: In conclusion, although SD had equivalent clinical outcomes with AT for the treatment of cubital tunnel syndrome, SD should be preferred due to having lower incidence of complications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To evaluate the outcome of patients with posterolateral tibial plateau fractures after open reduction and internal fixation with a fibula osteotomy-free posterolateral approach., Design: Retrospective chart and operation note review., Setting: A medical college-affiliated tertiary hospital., Materials and Methods: A retrospective chart and radiographic review of posterolateral tibial plateau fractures treated with a posterolateral approach between January 2006 and July 2010 was performed. The primary (ie, the total Rasmussen function score) and secondary (ie, the postoperative infection, knee deformity, and complications) outcomes were analyzed., Results: A total of 32 patients were identified for this study. Patients were followed for an average of 18.2 months (range, 12-36 months); the total Rasmussen function score was 24.8 ± 2.9 points. The results were rated as excellent (≥27 points) in 19 patients, good (20-26 points) in 11, and fair (10-19 points) in 2 patients. No wound infections, screw loosening or implant fracture, and nonunion, deformity, or fracture redisplacement were seen. Stretch injury of the common peroneal nerve was found in 1 patient, who obtained recovery 2 months after additional conservative management., Conclusions: Adequate open reduction and internal fixation with a fibula osteotomy-free posterolateral approach can attain a satisfactory clinical outcome for patients with posterolateral tibial plateau fractures., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Divergolides are a group of structurally unprecedented ansamacrolactam antibiotics with antibacterial and antitumor activities. A biosynthetic gene cluster predicted to encode the biosynthesis of divergolides was cloned and sequenced from endophytic Streptomyces sp. W112. The gene cluster of divergolides (div) spans a DNA region of 61-kb and consists of 20 open reading frames (ORFs) that encode polyketide synthases (PKSs), enzymes for the synthesis of AHBA and PKS extender units, and post-PKS modifications, proposed regulators, and putative transporters. Disruption of the AHBA synthase gene (divK) completely abolished the production of divergolides proved its involvement in the biosynthesis of divergolides. Bioinformatics analysis suggested that the regulatory gene div8 in div gene cluster might encode a positive regulator for the biosynthesis of divergolides. Constitutive overexpression of div8 improved the production of divergolides E, implying that div gene cluster maybe responsible for the biosynthesis of divergolides. These findings set the stage for fully investigating the biosynthesis of divergolides and rational engineering of new divergolide analogs by genetic modifications, and pave the way to further improve the production of divergolides., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To develop the single-tube one-step methylation variable position (MVP) analysis technology-single-tube post-digestion PCR-melting curve analysis (PDP-MCA)., Methods: Based on differentially methylated region (DMR) reported previously as the model, a set of primers with different melting temperatures of products in the two sides of MVP were designed. By using the FastDigest methylation-sensitive restriction enzyme (MSRE), DNA digestion, multiplex amplification, MCA detection and MCA profiles were performed in a single reaction tube. Same samples (peripheral venous blood, semen, and vaginal fluid, 5 samples each type) were tested by single-tube one step MVP and traditional MSRE-PCR MCA technology. To verify the feasibility of this method, the results were compared with that of the traditional technology. The MCA/HRM profiles of different samples were analyzed and compared., Results: When the melting temperature of the fragments had a differential of 2 degrees C, the MCA melting peaks separated well, and MCA detection after multiplex amplification was successful. The single-tube PDP-MCA assay was developed, which integrated multiple reactions (digestion, amplification and detection) into one tube. By this method, the sample-specific profiles and data were analyzed in 2 h, which is similar to that of the traditional method. The rapid classifications of the samples were also realized., Conclusion: Multiplex MVPs can be analyzed in a single closed-tube. The single-tube PDP-MCA technology is a simple, fast, and automatable method. It can be used for detection of DNA methylation variations.

Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including a complete gene cluster for the biosynthesis of cyclooctatin. This cluster contains four genes, cotB1-4, located in a 5-kb region. Optimization of fermentation medium for LZ35Δheng (SR107) led to the identification of cyclooctatin (1) and 16,17-dihydroxycyclooctatin (2), a new diterpene. The structures of these substances were elucidated on the basis of 1D-, 2D-NMR, and HRESIMS data. Cytotoxicity against MDA-MB-231 and A549 cell lines was also evaluated. Results demonstrated that gene cluster and pathway analysis are key to guided isolation of new natural products.

We objectively appraised available evidence regarding the threshold for the number of polymorphonuclear leukocytes required in frozen section tests used to diagnose periprosthetic infection. Pooled summary estimates for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (OR) were compared for ten and five polymorphonuclear leukocytes per high power field as the threshold. The total cohort included 1011 patients and the rate of infection was 19.2%. Although there was no difference in sensitivity or diagnostic OR, specificity was significantly higher for ten than for five polymorphonuclear leukocytes per high power field (p=0.007) In sum, a threshold of 10 polymorphonuclear leukocytes is better for diagnosing periprosthetic infections., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To explore the proportion of Th22 cells in peripheral blood of patients with aplastic anemia (AA) and evaluate its significance., Methods: From January 2011 to June 2012, a total of 47 AA patients were recruited and divided into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non-severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls (n = 12). The proportion of Th22 cells in peripheral blood of each group was evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was examined by reverse transcription-PCR (RT-PCR)., Results: The percentage of Th22 cells and the level of IL-22, TNF-α, IL-6 and IL-22 mRNA in group A (4.3% ± 1.4%, (57 ± 17) ng/L, (497 ± 123) ng/L, (323 ± 88) ng/L, 1.65 ± 0.51) and group C (2.6% ± 0.6%, (34 ± 10) ng/L, (314 ± 79) ng/L, (187 ± 45) ng/L, 0.92 ± 0.28) were significantly higher than that in control group (1.2% ± 0.3%, (19 ± 6) ng/L, (228 ± 50) ng/L, (134 ± 26) ng/L, 0.47 ± 0.09,all P < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA patients had similar results. The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group B (all P < 0.05). But the level of TGF-β in groups A and C were significantly lower than that in control group ((3.4 ± 1.1) and (5.8 ± 1.7) vs (9.7 ± 2.8) ng/L, P < 0.05). And the level of TGF-β in group A was lower than that of group B (P < 0.05)., Conclusions: The number of Th22 cells is elevated in AA patients. Th22 cells may be positively correlated with the development of AA. And a higher level of TNF-α, IL-6 and a lower level of TGF-β promote the differentiation of Th22 cells.

This study investigated the in vitro and in vivo antitumor effects of 5-[2,3-Dichloro-4-(2-methylene-1-oxobutyl) phenoxymethyl]-3-methyl-1,2,4- oxadiazole (6r), a novel ethacrynic acid (EA) derivative. The in vitro effect of 6r on cell proliferation of human colon, leukemia, prostate, lung, breast, ovarian and cervical tumor cell lines was assessed using MTT assay and the in vivo effect was determined with an SW620 xenografts nude mice model. The effect of 6r on expressions of GST P1-1 and apoptosis-related proteins were measured by western blotting and the effect on cell apoptosis was analysed by Hoechst 33258 nuclear staining as well as by cell surface staining of annexin V/propidium iodide. The effect on cell cycle was assessed by flow cytometry. Results showed that 6r inhibit proliferation of a range of human cancer cells in vitro and growth of SW620 tumor xenografts in vivo. The anti-proliferative effect of 6r is associated with cell apoptosis as a result of increased ratio of cellular Bax/bcl-2 expression and subsequent cytochrome-c and caspase-3 activation. Unlike EA, 6r did not show any influence on cellular GST P1-1 expression and its anti-proliferative action was associated with cell cycle arrest in G1/S-phase. In conclusion, 6r has the potential to be developed as a chemotherapeutic agent by induction of cell apoptosis but not regulating GST P1-1., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In order to investigate the contamination levels of groundwater in the irrigation districts of the lower reaches of Yellow River, fifty-nine groundwater samples collected from the irrigation districts of Henan and Shandong provinces, were analyzed. Health risks associated with eleven metals (Ba, Cd, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se and Zn) were assessed using water pollution index and USEPA health risk assessment model. The average concentrations of Fe with 0.496 mg x L(-1) and Zn with 0.445 mg x L(-1) were higher than the concentrations of other heavy metals. Concentrations of Fe, Mn, Se and Zn exceeded the relevant standards and the over-standard rates by 27.12%, 27.12%, 15.25% and 5.09%, respectively. Inverse distance weighted method was applied to estimate the unobserved points and their distribution maps were obtained, which indicated that areas of over-standard heavy metals were Wucheng country, Fan country, Dong'e country, Yucheng city and Guan country. Health risks of ingestion of water for all non-carcinogenic metals are higher than those of dermal absorption, while health risks of ingestion of water for carcinogenic metals is lower than those of dermal absorption. Among the health risks caused by the carcinogenic metals in drinking water and dermal absorption, the highest risks associated with Cr, are seven times and twenty-eight times as that of Cd, respectively, but both were significantly lower than the maximum allowance levels recommended by ICRP (5 x 10(-5) a (-1)). The non-carcinogenic metal risks( Ba, Cu, Fe, Mn, Mo, Ni, Pb, Se and Zn), ranging from 1.73 x 10(-13) to 3.46 x 10(-10) a(-1) in dermal absorption and from 1.13 x 10(-9) to 6.06 x 10(-8) a(-1) in drinking water, were much lower than the maximum allowance levels.

Objective: To investigate the proportion of Th22 cells in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and evaluate its significance., Methods: The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy (group 1), B-ALL and T-ALL patients in complete remission (ALL-CR, group 2) and healthy donors (group 3) were evaluated by flow cytometry. The cytokines IL-22, TGF-β, TNF-α and IL-6 in peripheral blood of each group were measured by enzyme-linked immunosorbent assay (ELISA). The levels of IL-22 mRNA in peripheral blood mononuclear cells of each group were examined by reverse transcription-PCR (RT-PCR)., Results: The percentages of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in B-ALL and T-ALL patients before therapy were (0.44 ± 0.10)%, (10.9 ± 3.4) ng/L, (110.7 ± 26.5) ng/L, (60.2 ± 13.8) ng/L, 0.17 ± 0.04 and (0.46 ± 0.11)%, (11.2 ± 3.5) ng/L, (114.6 ± 27.0) ng/L, (58.7 ± 12.4) ng/L, 0.19 ± 0.04, respectively; Which in B-ALL and T-ALL patients in complete remission were(0.59 ± 0.15)%, (14.3 ± 4.1) ng/L, (142.5 ± 32.7) ng/L, (83.7 ± 18.9) ng/L, 0.25 ± 0.06 and(0.60 ± 0.15)%, (14.6 ± 4.3) ng/L, (140.4 ± 31.4) ng/L, (81.4 ± 18.2) ng/L, 0.26 ± 0.06, significantly lower than those in healthy donors \[(1.24 ± 0.31)%, (19.7 ± 6.6) ng/L, (238.3 ± 50.4) ng/L, (138.0 ± 27.1) ng/L, 0.49 ± 0.09\] (P < 0.01). The percentages of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group l were lower than those in group 2 (P < 0.05), there was not significant difference between B-ALL and T-ALL (P > 0.05). But the levels of TGF-β in B-ALL and T-ALL patients before therapy \[(30.6 ± 8.2) ng/L, (31.4 ± 8.8) ng/L\] and in complete remission \[(24.2 ± 5.8) ng/L, (25.1 ± 6.1) ng/L\] were significantly higher than those in group 3\[(9.6 ± 2.8) ng/L\] (P < 0.01). However, the level of TGF-β in group 1 was higher than that of group 2 (P < 0.05), there was not significant difference between B-ALL and T-ALL (P > 0.05)., Conclusion: Both the number and function of Th22 cells reduced in ALL patients. Th22 cells might be negatively correlated with ALL progression. The lower levels of TNF-α and IL-6, and overexpression of TGF-β in ALL patients might suppress the differentiation of Th22 cells.

Aim: To investigate the change of Th22 cells in the peripheral blood of the patients with primary immune thrombocytopenia (ITP) and evaluate the significance of Th22 cells in ITP., Methods: The proportion of Th22 cells in the peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response after therapy (ITP-CR, group 2) and healthy donors (group 3) was evaluated by flow cytometry. The cytokines IL-22, TGF-β, TNF-α and IL-6 of each group were measured by ELISA. The level of IL-22 mRNA of each group was examined by RT-PCR., Results: The proportion of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group l and group 2 were significantly higher than those in group 3 (P<0.01). The proportion of Th22 cells and the levels of IL-22, TNF-α, IL-6 and IL-22 mRNA in group 2 were lower than those in group 1(P<0.05). But the level of TGF-β in group l [(3.27±1.02) ng/L] and group 2 [(5.41±1.69) ng/L] was significantly lower than that in group 3 [(9.65±2.78) ng/L] (P<0.01), and the level of TGF-β in group 1 was lower than that in group 2 (P<0.05)., Conclusion: In ITP patients, the number of Th22 cells and the levels of TNF-α and IL-6 increase, and the level of TGF-β decrease.

Objective: To explore the mechanism of immunomodulatory activity of triptolide on primary immune thrombocytopenia (ITP)patients-derived plasmacytoid dendritic cells (pDCs)., Methods: pDCs in peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response (ITP-CR, group 2) and healthy donors (group 3) were sorted by flow cytometry, then incubated with triptolide at 0, 5, 10 or 30 µg/L. After 24 hours, we collected the supernatants and then detected the concentrations of IFN-α, IL-6 and TNF-α using ELISA. After 5 days, the cultured cells were collected and CD11c, CD80 and CD86 expressions of myeloid dendritic cells (mDCs) were analyzed by flow cytometry, the morphology of mDC was observed by light microscope and electron microscope., Results: After incubation with triptolide at 10 µg/L, the levels of IFN-α, IL-6 and TNF-α in group 1 \[(451.32 ± 85.77) ng/L, (105.68 ± 23.85) ng/L and (135.78 ± 30.62) ng/L\] and group 2 \[(391.71 ± 72.49) ng/L, (84.73 ± 17.77) ng/L and (108.16 ± 23.21) ng/L\] were significantly higher than those in group 3 \[(335.51 ± 67.54) ng/L, (73.62 ± 21.82) ng/L and (95.58 ± 32.85) ng/L\] (all P < 0.05); the levels of IFN-α, IL-6 and TNF-α in group 1 were significantly higher than those in group 2 (all P < 0.05) in a dose-dependent manner (P < 0.05). CD11c, CD80 and CD86 expressions of mDC in group1 and group 2 were significantly higher than those in group 3 (all P < 0.05); CD11c, CD80 and CD86 expressions of mDC in group 1 were significantly higher than those in group 2 (all P < 0.05) also in a dose-dependent manner (all P < 0.05). Triptolide could inhibit pDCs from differentiation into mDCs, the latter displayed more immature morphology than untreated-pDCs., Conclusion: Triptolide could decrease the immune function of pDCs from ITP, inhibit pDCs from differentiation and maturation.

Purpose: To study the effects of percutaneous reconstruction plate internal fixation in the treatment of unstable sacral fractures., Methods: Percutaneous reconstruction plate internal fixation was applied on 21 cases of unstable sacral fracture (15 males and six females, at age range of 16-65 years, mean 38.3 years) including four cases of Denis Zone I, 14 cases of Zone II and three cases of Zone III. In operation, an arc incision (about 3-5 cm long) was made along the iliac crest on the outside border of posterior superior iliac spine (PSIS) on both sides, and then the plate was transported from the wounded side to the opposite one through the subcutaneous tunnel., Results: The mean incision length, operation time, intraoperative blood loss was 4.3 cm, 45.2 min, and 160.8 ml respectively. All these patients were followed up for 12-33 months (average 16.3 months), which showed no incision infection, intraoperative neurovascular injury, internal fixation loose or breakage, disunion, or obvious lower limb length inequality. The function result was rated as excellent in six cases, good in 12 and fair in 3, with excellence rate of 85.7%, according to the Majeed scoring system., Conclusion: Percutaneous reconstruction plate internal fixation is an ideal surgical approach to unstable sacral fractures, as it is easy, safe, causing less trauma and fewer complications, and conducive to quicker recovery.

There is a lack of ideal clinical classification systems for posterior tibial plateau fractures, and they need to be perfected in clinical practices. There are controversies over surgical approaches due to special characters of posterior tibial plateau fractures. It is difficult for the conventional techniques and approaches to achieve satisfactory reduction and fixation. A modified posterior approach is an ideal approach for the treatment of posterior tibial plateau fractures. This paper summarizes the classification, approach and internal fixation of posterior tibial plateau fractures.