A Systematic Review and Meta-analysis of Renin-angiotensin System Inhibitors and Angiotensin Receptor Neprilysin Inhibitors in Preventing Recurrence After Atrial Fibrillation Ablation.

ABSTRACT: To systematically evaluate the efficacy and safety of renin-angiotensin system inhibitors (RASIs) and angiotensin receptor neprilysin inhibitors in preventing the recurrence of atrial fibrillation after atrial fibrillation ablation, we have written this meta-analysis. We systematically searched randomized controlled trials or cohort studies on RASIs and angiotensin receptor neprilysin inhibitor-sacubitril/valsartan (SV) in preventing the recurrence of atrial fibrillation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Afterward, the meta-analysis was performed using RevMan 5.3 software. This meta-analysis results showed that the recurrence rate of atrial fibrillation after ablation in subjects using RASIs was lower than that in subjects not using them [relative risk = 0.85, 95% confidence interval (CI) (0.72-0.99), P = 0.03]; the recurrence rate in subjects using SV was lower than that in subjects using RASIs [RR= 0.50, 95% CI (0.37-0.68), P < 0.00001]. These results show that both the use of RASIs and SV can prevent the recurrence of after atrial fibrillation ablation, among which the use of SV is more effective.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

If we should remove internal fixation devices for rib fractures?

BACKGROUND: Internal fixation for rib fractures has been widely carried out worldwide, and its surgical efficacy has been recognized. However, there is still controversy about whether implant materials need to be removed. At present, the research on this topic is still lacking at home and abroad. Therefore, in this study, the patients undergoing removal of internal fixation for rib fractures in our department within one year were followed up, to statistically analyze implant-related complications, postoperative complications and postoperative remission rate. METHODS: A retrospective analysis was conducted on 143 patients undergoing removal of internal fixation for rib fractures from 2020 to 2021 in our center. The implant-related complications, postoperative complications and postoperative remission rate of patients with internal fixation were analyzed. RESULTS: In this study, a total of 143 patients underwent removal of internal fixation, among which 73 suffered from preoperative implant-related complications (foreign-body sensation, pain, wound numbness, sense of tightness, screw slippage, chest tightness, implant rejection), and 70 had no post operative discomfort but asked for removal of internal fixation. The average interval between rib fixation and removal was 17 ± 9.00 (months), and the average number of removed materials was 5.29 ± 2.42. Postoperative complications included wound infection (n = 1) and pulmonary embolism (n = 1). of the 73 patients with preoperative implant-related complications, the mean postoperative remission rate was 82%. Among the 70 patients without preoperative discomfort, the proportion of discomforts after removal was 10%. No perioperative death occurred. CONCLUSION: For patients with internal fixation for rib fractures, removal of internal fixation can be considered in the case of implant-related complications after surgery. The corresponding symptoms can be relieved after removal. The removal presents low complication rate, and high safety and reliability. For patients without obvious symptoms, it is safe to retain the internal fixation in the body. For the asymptomatic patients who ask for removal of internal fixation, the possible risk of complications should be fully informed before removal.

Mouse nerve growth factor suppresses neuronal apoptosis in valproic acid-induced autism spectrum disorder rats by regulating the phosphoinositide-3-kinase/serine/threonine kinase signaling pathway.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restrictive behaviors. Mouse nerve growth factor (mNGF), a neurotrophic factor, is critical for neuronal growth and survival, and the mNGF treatment is considered a promising therapy for neurodegeneration. In light of this, we aimed to evaluate the effect of mNGF on neurological function in ASD. METHODS: An ASD rat model was established by intraperitoneal injection of valproic acid (VPA). Social behavior, learning, and memory of the rats were measured. TdT-mediated dUTP Nick-end labeling and Nissl assays were performed to detect neuronal apoptosis and survival in the hippocampus and prefrontal cortex. Apoptosis-related proteins and oxidative stress markers were detected. RESULTS: mNGF improved locomotor activity, exploratory behavior, social interaction, and spatial learning and memory in VPA-induced ASD rats. In the hippocampus and prefrontal cortex, mNGF suppressed neuronal apoptosis, increased the number of neurons, superoxide dismutase, and glutathione levels, and decreased reactive oxygen species, nitric oxide, TNF-α, and IL-1ß levels compared with the VPA group. In addition, mNGF increased the levels of Bcl-2, p-phosphoinositide-3-kinase (PI3K), and p-serine/threonine kinase (Akt), and decreased the levels of Bax and cleaved caspase-3, while the PI3K inhibitor LY294002 reversed these effects. CONCLUSION: These data suggest that mNGF suppressed neuronal apoptosis and ameliorated the abnormal behaviors in VPA-induced ASD rats, in part, by activating the PI3K/Akt signaling pathway.

Surgical treatment of costal cartilage fractures with titanium plate internal fixation.

BACKGROUND: This study aim to evaluate surgical procedures for titanium plate internal fixation of costal cartilage fractures with displacement or nonunion. METHODS: From January 2019 to October 2020, 13 patients with costal cartilage fractures were treated with titanium plate internal fixation in the thoracic surgery department of the Shanghai Sixth People's Hospital. Pain severity scale scores and respiratory function were evaluated preoperatively and postoperatively. All the patients had a 6-month follow-up for treatment evaluation. RESULTS: The mean hospital length of stay was 10.7 days. A statistically significant difference (P < 0.05) was found between preoperative and postoperative pain severity scores (7.69 vs. 5.00). VC (24.6% vs. 44.5%) and FEV1 (25.3% vs. 44.0%) were also significantly different before operation and after operation (P < 0.05). At follow-up, healing of the nonunion or fracture was confirmed in all the cases. CONCLUSION: The rigid titanium plate application ensured a safe and easy management of costal cartilage fractures and nonunion with a good prognosis as compared with other methods.

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses.

OBJECTIVE: Emerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism. METHOD: Pregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28-48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44-48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured. RESULT: Electroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2. CONCLUSION: These data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer.

Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1-2×109 cells and a dose-climbing strategy. Hemoglobin, platelets, white cell count, creatinine or liver enzyme values, coagulation function, kidney and heart function were not significantly affected over the duration of therapy. Two of the three enrolled patients showed potentially drug-related grade 1 and 2 weakness, and no other adverse events were observed. Of the three enrolled patients, one had stable disease and two showed disease progression. The patient with favorable clinical efficacy had better immune response as measured by 6B11-OCIK proliferation capacity, activation ability of CD3+CD8+ tumor-specific cytotoxic T lymphocytes and CD3+CD56+ cytokine-induced killer cells, and tumor cell killing efficiency. Changes in circulating tumor cells after treatment were consistent with serum level CA125 in the patient with stable disease (both decreased), while differences were observed in the two patients with disease progression (increased CA125 in both and decreased CTC in the patient with better immune response), suggesting that variation of circulating tumor cells was more consistent with immune response and reflected efficacy directly. This preliminary study suggested that autologous 6B11-OCIK treatment was safe and had potential clinical efficacy against ovarian cancer. Patients with better immune response had more favorable efficacy. In addition to imaging, CA125 and immunophenotypes, CTC monitoring may represent a potential indicator of immunotherapy response.

Cisplatin loaded multiwalled carbon nanotubes reverse drug resistance in NSCLC by inhibiting EMT.

BACKGROUND: Lung cancer is one of the important health threats worldwide, of which 5-year survival rate is less than 15%. Non-small-cell lung cancer (NSCLC) accounts for about 80% of all lung cancer with high metastasis and mortality. METHODS: Cisplatin loaded multiwalled carbon nanotubes (Pt-MWNTS) were synthesized and used to evaluate the anticancer effect in our study. The NSCLC cell lines A549 (cisplatin sensitive) and A549/DDP (cisplatin resistant) were used in our in vitro assays. MTT was used to determine Cancer cells viability and invasion were measured by MTT assay and Transwell assay, respectively. Apoptosis and epithelial-mesenchymal transition related marker proteins were measured by western blot. The in vivo anti-cancer effect of Pt-MWNTs were performed in male BALB/c nude mice (4-week old). RESULTS: Pt-MWNTS were synthesized and characterized by X-ray diffraction, Raman, FT-IR spectroscopy and scan electron microscopy. No significant cytotoxicity of MWNTS was detected in both A549/DDP and A549 cell lines. However, Pt-MWNTS showed a stronger inhibition effect on cell growth than free cisplatin, especially on A549/DDP. We found Pt-MWNTS showed higher intracellular accumulation of cisplatin in A549/DDP cells than free cisplatin and resulted in enhanced the percent of apoptotic cells. Western blot showed that application of Pt-MWNTS can significantly upregulate the expression level of Bax, Bim, Bid, Caspase-3 and Caspase-9 while downregulate the expression level of Bcl-2, compared with free cisplatin. Moreover, the expression level of mesenchymal markers like Vimentin and N-cadherin was more efficiently reduced by Pt-MWNTS treatment in A549/DDP cells than free cisplatin. In vivo study in nude mice proved that Pt-MWNTS more effectively inhibited tumorigenesis compared with cisplatin, although both of them had no significant effect on body weight. CONCLUSION: Pt-MWNT reverses the drug resistance in the A549/DDP cell line, underlying its possibility of treating NSCLC with cisplatin resistance.

Nonintubated minimally invasive chest wall stabilization for multiple rib fractures: a prospective, single-arm study.

BACKGROUND: Nonintubated video-assisted thoracoscopic surgery has been widely reported in the past decade, while nonintubated chest wall stabilization has not been reported previously. The aim of this study was to evaluate the safety and feasibility of nonintubated minimally invasive chest wall stabilization in patients with multiple rib fractures. METHODS: We conducted a prospective, single-arm, observational study. In this prospective study, 20 consecutive patients with multiple rib fractures were treated using nonintubated minimally invasive chest wall stabilization. RESULTS: Minimally invasive chest wall stabilization was mostly performed for lateral rib fractures in this study (n = 8). The mean operation time was 92.5 min, and the mean blood loss was 49 ml. No patient required conversion to tracheal intubation. The mean extubation time of the laryngeal mask was 8.9 min; the mean postoperative fasting time was 6.1 h; the mean postoperative hospital stay was 6.2 days; the mean amount of postoperative drainage was 97.5 ml; the mean postoperative pain score was 2.9 points at 6 h, 2.8 points at 12 h, and 3.0 points at 24 h; and the mean postoperative nausea and vomiting score was 1.9 points at 6 h, 1.8 points at 12 h, and 1.7 points at 24 h. CONCLUSIONS: Nonintubated minimally invasive chest wall stabilization is safe and feasible in carefully selected patients. Further studies with a large sample size are warranted. TRIAL REGISTRATION: ChiCTR1900025698 . Registered on 5 September 2019.

Comparison of minimally invasive surgery for non-flail chest rib fractures: a prospective cohort study.

BACKGROUND: To evaluate therapeutic efficacy of minimally invasive and small incision surgery [minimally invasive surgery (MIS)] in patients with non-flail chest rib fractures through a prospective cohort study. METHODS: This study included 98 patients with non-flail chest rib fractures (≥3 displaced fractures) and 66 patients undergoing MIS served as the experimental group and 32 patients receiving conservative treatment served as the matched control group. Pain index and indicators of pulmonary function [vital capacity (VC); forced expiratory volume in one second (FEV1); peak expiratory flow (PEF)] for the two groups were assessed and compared at the time of admission and before discharge. In addition, duration of pain, time required for the patient to regain the ability to perform daily self-care, mental labor, and moderate-to-severe physical labor, and duration of chest discomfort were measured during long-term follow-up and compared between the two groups. RESULTS: There were also no significant differences (P>0.05) in pain index (8 vs. 8) or indicators of pulmonary function (VC: 31.0% vs. 26.5%; FEV1: 29.9% vs. 26.7%; PEF: 15.2% vs. 12.0%) were found between the MIS and conservative treatment groups at the time of admission; while pain index (3 vs. 6), VC (42.1% vs. 35.3%), and FEV1 (44.2% vs. 35.9%) were significantly different between the two groups (P<0.05) but not in PEF (21.2% vs. 19.6%) before discharge. Long-term follow-up showed that duration of pain, time required for the patient to regain the ability to engage in daily self-care, mental labor, and moderate-to-severe physical labor, and duration of chest discomfort in the MIS group were significantly more improved than in the conservative treatment group (P<0.05). CONCLUSIONS: MIS was a simple and safe treatment that significantly relieved chest pain and rapidly restored pulmonary function and improved the long-term quality of life of patients with non-flail chest rib fractures of ≥3 ribs with displacement.

Expanded activated autologous lymphocyte infusions improve outcomes of low- and intermediate-risk childhood acute myeloid leukemia with low level of minimal residual disease.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

Upregulated lncRNA CASC9 Contributes to Progression of Non-Small Cell Lung Cancer Through Inhibition of miR-335-3p and Activation S100A14 Expression.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a deadly cancer type worldwide and the main sub-type of lung cancer. Cancer susceptibility candidate-9 (CASC9) was reported to be a key player in cancer progression. However, its function and underlying mechanism in NSCLC remain unclear. MATERIALS AND METHODS: Expression level of CASC9 in NSCLC tissues and cells was measured with RT-qPCR. Biological roles of CASC9 in NSCLC were analyzed with a series of in vitro experiments. Potential mechanisms of CASC9 in NSCLC were analyzed by predicting and validating the possible targets of CASC9 in NSCLC. RESULTS: In this study, we found CASC9 expression was upregulated in NSCLC tissues and cell lines. High CASC9 expression was identified as a predictor for poorer overall survival of NSCLC patients. Furthermore, functional assays showed CASC9 knockdown suppressed NSCLC cell proliferation, migration, and invasion, while CASC9 overexpression caused opposite effects. We also found microRNA-335-3p (miR-335-3p) could act as a target of CASC9 in NSCLC and the inhibition effect of CASC9 knockdown on NSCLC progression required the activity of miR-335-3p. In addition, we identified S100 calcium-binding protein A14 (S100A14) acts as a target of miR-335-3p. DISCUSSION: Taken together, our study suggested CASC9 could promote NSCLC progression via miR-335-3p/S100A14 axis. The CASC9/miR-335-3p/S100A14 regulatory triplets identified in this work might provide new therapeutic strategies for NSCLC treatment.

LncRNA DLEU2 accelerates the tumorigenesis and invasion of non-small cell lung cancer by sponging miR-30a-5p.

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of non-small cell lung cancer (NSCLC). However, how lncRNA deleted in lymphocytic leukaemia 2 (DLEU2) contributes to NSCLC remains undocumented. The clinical significance of lncRNA DLEU2 and miR-30a-5p expression in NSCLC was analysed by using fluorescence in situ hybridization and TCGA cohorts. Gain- and loss-of-function experiments as well as a NSCLC tumour model were executed to determine the role of lncRNA DLEU2 in NSCLC. DLEU2-sponged miR-30a-5p was verified by luciferase reporter, and RIP assays. Herein, the expression of lncRNA DLEU2 was elevated in NSCLC tissues, and its high expression or low expression of miR-30a-5p acted as an independent prognostic factor of poor survival and tumour recurrence in NSCLC. Silencing of lncRNA DLEU2 repressed the tumorigenesis and invasive potential of NSCLC, whereas re-expression of lncRNA DLEU2 showed the opposite effects. Furthermore, lncRNA DLEU2 harboured a negative correlation with miR-30a-5p expression in NSCLC tissues and acted as a sponge of miR-30a-5p, which reversed the tumour-promoting effects of lncRNA DLEU2 by targeting putative homeodomain transcription factor 2 in NSCLC. Altogether, lncRNA DLEU2 promoted the tumorigenesis and invasion of NSCLC by sponging miR-30a-5p.

Necessity of thoracotomy in pulmonary metastasis of osteosarcoma.

BACKGROUND: With the popularization of minimal invasive surgery, video-assisted thoracoscopic surgery (VATS) is gradually replacing conventional thoracotomy for lung cancer and is even used for osteosarcoma patients with pulmonary metastasis. In this study, we characterized the need for open surgery by comparing computer tomography (CT) diagnosis and postoperative pathology of patients with pulmonary metastases of osteosarcoma. METHODS: A retrospective analysis was carried out on patients with underwent surgery for pulmonary metastatic osteosarcoma admitted to our hospital between January 2008 and July 2018. The numbers of pulmonary metastatic nodules suspected by preoperative CT scan were calculated in addition to the number of nodules which were resected and pathologically confirmed to be metastatic during surgery. The Spearman correlation coefficient between the number of nodules on preoperative CT scan and the number of lesions pathologically confirmed was calculated. RESULTS: In total, 69 patients undergoing 96 thoracotomy operations were included in this study. The median interval between preoperative CT examination and operation was 7 days (range, 1-44 days). The median number of the suspected nodules on preoperative CT and the pathologically positive metastases resected during operation were 1 and 3, respectively. Remarkably, 36 (37.5%) thoracotomies revealed that more metastatic nodules were detected during thoracotomy than preoperative CT scans. CONCLUSIONS: Preoperative CT examination omits a few small pulmonary metastases of osteosarcoma and there is rare progress in recent years. Therefore, we recommend that patients with pulmonary metastases of undergo thoracotomy to locate and resect all metastases as much as possible through intraoperative direct palpation.

Simultaneous Surgical Treatment of Sternum and Costal Cartilage Fractures.

Studies have confirmed that, for severe flail chest or sternal fractures and even multiple rib fractures, surgical treatment can effectively reduce hospital stay and relieve chest wall pain. However, fixation of multiple costal cartilage fractures in such a small area is a challenge if an internal fixator is simply placed directly on the sternum. This case report shares a method of simultaneous fixation of multiple costal cartilage and sternal fractures through a small incision, and it is also appropriate for multiple costal cartilage fractures without sternal fracture.

Reconstruction of anterior chest wall: a clinical analysis.

OBJECTIVE: To investigate the methods and clinical efficacy of reconstruction of chest defects with titanium sternal fixation system after the surgical resection of sternal tumors. METHODS: A total of 6 patients with sternal tumor who were diagnosed and underwent resection and repair of the chest wall defects by titanium plates system, from 2017.3 to 2017.11 in our hospital were reviewed. Their pathological types, surgical reconstruction methods, follow-up results were analyzed. RESULTS: Six cases of sternal tumor were completely resected and the sternums were reconstructed with titanium sternal fixation system. There was no operative death, postoperative chest wall deformity, abnormal breathing or complications of respiratory circulation. After 3 to 10 months of follow-up, there was no loose screw or plate exposure. Not only the thoracic appearances were good, but patients' satisfaction was high. CONCLUSIONS: Surgical resection is the best treatment for sternal tumors, no matter it is benign or malignant. Titanium sternal fixation system combine with other soft materials can reconstruct the chest wall well after resection, and this technique is efficient as well as easy to learn.

Crystal structure of tissue factor in complex with antibody 10H10 reveals the signaling epitope.

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation through sequential binding and activation of coagulation factors VII (FVII) and X (FX). In addition, through activation of G-protein-coupled protease activated receptors (PARs) TF induces cell signaling that is related to cancer, angiogenesis and inflammation. Monoclonal antibodies (mAbs) proved to be a useful tool for studying the interplay between TF signaling and coagulation. MAb 10H10 is unique in that it blocks the signaling pathway and thus inhibits angiogenesis and tumor growth without interfering with coagulation. It was also presumed that mAb 10H10 recognizes the cryptic pool of TF devoid of procoagulant activity. The crystal structure of the 10H10 Fab was determined in the absence and in the presence of the TF extracellular domain (ECD). The structures show that the antibody operates by the key-and-lock mechanism causing no conformational changes in either Fab or TF. The TF:10H10 interface is extensive and includes five segments of TF in both the N-terminal and C-terminal domains of the ECD. Neither the known epitope of FVII, nor the putative epitope of FX overlaps with the 10H10 binding site. The 10H10 epitope points to the likely location of the PAR2 exosite. It is also the hypothetical site of TF interaction with integrins that may play a major role in the encryption-decryption process.

Treatment of traumatic sternal fractures with titanium plate internal fixation: a retrospective study.

BACKGROUND: This study aim to evaluate surgical procedures for titanium plate internal fixation of sternal fractures with displacement or nonunion. METHODS: From January 2010 to December 2014, 64 patients with sternal fractures were treated with titanium plate internal fixation in the thoracic surgery department of the Shanghai Sixth People's Hospital. Pain severity scale scores were analyzed preoperatively and postoperatively. All the patients had a 2-month follow-up for treatment evaluation. RESULTS: The mean hospital length of stay was 16.89 days. Forty-five patients underwent surgery for combined injuries. A statistically significant difference (P < 0.05) was found between preoperative and postoperative pain severity scores (7.74 ± 0.89 vs. 3.80 ± 0.79, respectively). At follow-up, healing of the nonunion or fracture was confirmed in all the cases. CONCLUSION: The rigid titanium plate application ensured a safe and easy management of traumatic sternal fractures and nonunion with a good prognosis as compared with other methods.

A blockade of PD-L1 produced antitumor and antimetastatic effects in an orthotopic mouse pancreatic cancer model via the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression. In this study, we investigated the potential therapeutic effect of blockading PD-L1 expression on the progression of pancreatic cancer and its spontaneous liver metastases in vivo by inhibiting the PI3K/Akt/mTOR signaling pathway. METHODS: We investigated the effect of blockading PD-L1 in an orthotopic pancreatic cancer mouse model. The pancreatic tumor weights and inhibition ratios were determined after treatment with antimouse PD-L1 antibody for 5 weeks. We used immunohistochemistry methods to investigate PD-L1 expression in pancreatic cancer tissue and spontaneous liver metastasis tissue. The levels of mRNA and protein expression for various components involved in the PI3K/Akt/mTOR signaling pathway as well as for matrix metalloproteinases-2 and -9 (MMP2 and MMP9) were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods, respectively. RESULTS: Blockading PD-L1 significantly inhibited tumor growth and decreased the levels of PD-L1 expression in tumor tissue. Furthermore, the levels of PTEN mRNA and protein expression were elevated, while the levels of phospho-Akt (p-Akt) and phospho-mTOR (p-mTOR) protein were decreased in pancreatic cancer and liver metastasis tissues after establishing a PD-L1 blockade. In addition, a PD-L1 blockade decreased the levels of MMP2 and MMP9 mRNA and protein expression in tumor tissues. CONCLUSION: Our results suggest that a blockade of PD-L1 may inhibit the growth and metastasis of pancreatic cancer by modulating the PI3K/Akt/mTOR pathway.

[Preliminary study on hepatotoxicity induced by dioscin and its possible mechanism].

Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.