Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

[The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation].

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

[Hemophagocytic syndrome secondary to COVID-19: a case report and literature review].

Objective: To improve the awareness of hemophagocytic syndrome(HPS) secondary to COVID-19 (COVID-sHPS). Methods: We reported an adult case of COVID-sHPS, including clinical presentation, laboratory examinations, histopathological findings, treatment strategy, and outcome. We also conducted literature research in PubMed database and Wanfang database using the keywords "COVID-19" and "hemophagocytic syndrome" and subsequently summarized relevant literature. Results: A 49-year-old man was admitted to our hospital after 4 weeks of recurrent fever. Prior to this hospitalization, he had received an empiric combination therapy with antibiotics and antiviral drugs against SARS-CoV-2. His vital signs were within the normal range and no abnormalities were found on physical examination on admission. After admission, throat swab nucleic acid tests were weakly positive for SARS-CoV-2, and negative for influenza and respiratory syncytial virus. Blood nucleic acid tests for cytomegalovirus and EB virus were negative, as was blood mNGS. Laboratory tests showed a series of abnormalities, including leukopenia, thrombocytopenia, low fibrinogen, elevated serum ferritin, elevated transaminase, decreased NK cell activity, and hemophagocytosis in bone marrow. According to the HPS-2004 diagnostic criteria, he was diagnosed with hemophagocytic syndrome, which was high likely to be caused by COVID-19 infection due to the lack of evidence of genetic risk factors and other clear triggers. He was initially treated with dexamethasone at a dose of 10 mg·m-2·d-1 and his condition improved rapidly. The literature search identified twenty-three articles on COVID-sHPS, 22 of which were in English. A total of 89 patients had COVID-sHPS and 55 (61.7%) were male. COVID-sHPS could occur at any age, but mainly in adults (86/89, 96%). Fever was reported in the literature with a clear description of the course of the disease. Most HPS occurred during the acute phase of COVID-19, but 3 patients developed HPS during the convalescent phase. Almost all reported cases presented with increased ferritin, elevated transaminases, elevated triglycerides, and cytopenia, mainly anemia and thrombocytopenia. In the retrieved literature, HS-score≥169 was frequently used to diagnose COVID-sHPS, and glucocorticoid in combination with immunoglobulin was the most common treatment strategy. COVID-sHPS had a poor prognosis and a high mortality rate (84.2%, 75/89). Conclusions: The prognosis of COVID-sHPS is poor, so clinicians should raise their awareness of the disease, identify high-risk suspected populations, and arrange reasonable relevant examinations for definite diagnosis and early initial treatment to improve their outcome.

[Screening for occult cancer in patients with unprovoked venous thromboembolism].

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is the third most common cardiovascular disease. Unprovoked VTE can be the initial presentation of occult cancer. Up to 10% of patients with unprovoked VTE are diagnosed with cancer within a year. Cancer screening in patients with unprovoked VTE is beneficial for early cancer diagnosis and treatment, which may theoretically reduce cancer-related morbidity and mortality. The epidemiology of occult cancer in patients with unprovoked VTE, screening strategies originated from evidence-based medicine, risk factors of cancer and different models of risk assessment are reviewed in this article.

Author Correction: Circular RNA circ-PRKCI promotes cell proliferation and invasion by binding to microRNA-545 in gastric cancer.

Correction to: European Review for Medical and Pharmacological Sciences 2019; 23 (21): 9418-9426-DOI: 10.26355/eurrev_201911_19435-PMID: 31773680, published online on 15 November 2019. After publication, the authors applied to change Figure 1E stating that "gastric cancer was observed from patients underlying response at Renmin Hospital of Wuhan University from March 2015 to March 2016. By the time of submission, the survival time of follow-up was only 2 years. From the 2-year follow-up data, we found that high expression of CIRC PRKCI was positively associated with a poor prognosis of GC patients". The authors claim that there is no serious change in the conclusion of the article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19435.

FOXN2 suppresses the proliferation and invasion of human hepatocellular carcinoma cells.

OBJECTIVE: The aim of this study was to explore the roles of FOXN2 (Fork head Box N2) in mediating the proliferation and invasion of hepatocellular carcinoma (HCC) cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine expression of FOXN2 in HCC tissues and cells. Transfection of plasmid containing FOXN2 was used to exogenously overexpress FOXN2 in vitro. Cell Counting Kit-8 (CCK-8) assay and transwell assay were applied to detect the proliferation and invasion of HCC cells, respectively. RESULTS: FOXN2 expression decreased significantly in both HCC tissues and cells (p<0.05). Upregulation of FOXN2 significantly inhibited the proliferation and invasion of HCC cells (p<0.05). CONCLUSIONS: FOXN2 acts as a regulator in the progression of HCC. Our findings suggest that FOXN2 may be a novel therapeutic monitoring and prognosis biomarker in HCC.

Both Caspase and Calpain are Involved in Endoplasmic Reticulum-Targeted BNIP3-Induced Cell Death.

Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3-induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.

MiR-769-5p inhibits cancer progression in oral squamous cell carcinoma by directly targeting JAK1/STAT3 pathway.

Oral squamous cell carcinoma (OSCC) is the most common human malignancy worldwide with a high mortality rate. MiR-769-5p has been reported to be downregulated in tissues and blood of OSCC patients. However, the exact roles and pathogenesis of miR-769-5p involved in OSCC remain unclear. The expressions of miR-769-5p and Janus kinase (JAK1) in OSCC tissues and cells were assessed by RT-qPCR and western blot assay. Expressions of apoptotic-related (Bcl-2, Bax, and cleaved-caspase 3) and EMT-associated proteins (MMP9, E-cadherin, N-cadherin, and Vimentin) were detected by western blot assay. The effect of miR-769-5p and JAK1 on proliferation, migration, invasion, and apoptosis was evaluated by CCK-8, transwell, and flow cytometry assays, respectively. The binding interaction of miR-769-5p and JAK1 were predicted by TargetScan and demonstrated by dual-luciferase reporter assays. The volume and weight of the tumor were measured in the subcutaneous transplantation experiment. MiR-769-5p was downregulated, and JAK1 was upregulated in OSCC tissues and cells. MiR-769-5p restrained Bcl-2, MMP9, N-cadherin, and Vimentin protein level and accelerated Bax, cleaved-caspase 3 and E-cadherin protein level, while JAK1 partly overturned these effects. Also, miR-769-5p suppressed proliferation, migration, invasion, and increased apoptosis of OSCC, while the reintroduction of JAK1 abolished these effects. Moreover, JAK1 was verified to be the target of miR-769-5p. In addition, miR-769-5p inhibited the development of OSCC cells in vivo. These results indicate that miR-769-5p suppressed OSCC cell development via targeting the JAK1/STAT3 pathway, providing an underlying therapeutic method for OSCC.

[Idiopathic pleuroparenehymal fibroelastosis: report of one case and review of literature].

Objective: To analyze the clinical,imaging and pathological features of Pleuroparenehymal fibroelastosis (PPFE). Methods: The clinieal data of a patient diagnosed as PPFE admitted in department of Respiratory and Critical Care Medicine,Beijing Hospital in April 2017 were reported and the related literatures were reviewed.With "pleuroparenehymal fibroelastosis" as the search terms, and the search time before October 1st 2017 for Wanfangdata, China National Knowledge Infrastructure(CNKI), and PubMed. Results: The patient was a 46-year-old male presented with cough, shortness of breath after exercise.A CT scan of the chest revealed bilateral, irregular pleural thickening with upper lobe predominance.After 3 years of antituberculosis treatment,the disease progressed. A diagnosis of pleuroparenehymal fibroelastosis (PPFE) was confirmed by CT guided lung biopsy. A total of 132 cases were reported (including 1 case in Chinese). 88 of them were confirmed by pathology with detailed data.Clinical data of 89 reported cases with PPFE including 48 males and 41 females aged 13 to 85 years were enrolled and analyzed in the study.The common symptoms were dyspnea(62%, 55 cases),cough(58%, 52 cases),recurrent respiratory tract infection(17%, 15 cases).The main CT features are reported:pleural thickening(87%,77 cases), recurrent pneumothorax(52%,46 cases), traction bronchiectasis(30%, 27 cases),subpleural comsolidation(20%, 18 cases). All patients were proven PPFE by biopsy.34 cases received corticosteroid, 5 cases received lung transplant operation.40 cases died during the follow-up from 4 month to 84 month. Conclusions: Pleuroparenehymal fibroelastosis is a rare disease.The imaging findings were dominated by both upper lobes. Lung biopsy might be necessary. PPFE is often misdiagnosed as pulmonary tuberculosis/obsolete pulmonary tuberculosis,asbestosis,connective tissues disease and Drug-induced pneumonitis.There was no consensus on the treatment.

Circular RNA circ-PRKCI promotes cell proliferation and invasion by binding to microRNA-545 in gastric cancer.

OBJECTIVE: The carcinogenic effects of circular RNA circ-PRKCI have been recognized in a variety of malignancies. However, the exact biological function of circ-PRKCI in gastric cancer has not been fully elucidated. Therefore, the aim of this study was to explore the expression of circ-PRKCI in gastric cancer (GC) and to investigate its potential regulation mechanism in the pathogenesis and progression of GC. PATIENTS AND METHODS: The expression of circ-PRKCI in 50 GC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Statistical methods were used to analyze the relation between circ-PRKCI expression and overall survival rate of patients. The effect of circ-PRKCI on GC cell proliferation was examined by cell counting kit-8 (CCK-8) and cell colony formation assays. Meanwhile, the effect of circ-PRKCI on the invasion ability of GC cells was determined by transwell invasion assay. Flow cytometry was used to detect the apoptosis of GC cells. Bioinformatics was used to search for miRNAs that might have direct effects with circ-PRKCI. In addition, the binding of circ-PRKCI to microRNA-545 was validated using Dual-Luciferase reporter gene assay. RESULTS: Circ-PRKCI was significantly highly expressed in GC tissues, as well as cell lines. High expression of circ-PRKCI was positively associated with a poor prognosis of GC patients. Overexpression of circ-PRKCI significantly promoted the proliferation and invasion of GC cells, whereas reduced the proportion of apoptotic GC cells. Subsequent Dual-Luciferase reporter gene assay revealed that circ-PRKCI could bind to microRNA-545 and inhibit its expression in GC cells. These results indicated that circ-PRKCI might promote the development of GC by adsorbing microRNA-545 in a sponge manner. CONCLUSIONS: Circ-PRKCI can be used as a potential prognostic indicator of GC, providing a new perspective for the potential bio-molecular mechanism in GC.

Circ_0000064 adsorption of microRNA-143 promotes malignant progression of hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to investigate the expression characteristics of circ_0000064 in hepatocellular carcinoma, and to further explore the underlying mechanism. PATIENTS AND METHODS: Real time quantitative-Polymerase Chain Reaction (qPCR) was used to detect the expression of circ_0000064 in 42 hepatocellular carcinoma tissues and adjacent normal tissues. Meanwhile, the relationship between circ_0000064 expression and clinical indicators, as well as the prognosis of patients with hepatocellular carcinoma, were detected. QPCR was applied to measure circ_0000064 level in hepatocellular carcinoma cell lines as well. Subsequently, the circ_0000064 knockdown model was successfully constructed using lentivirus in hepatocellular carcinoma cell lines. Cell counting kit-8 (CCK-8), colony formation assay, and flow apoptosis were performed to analyze the influence of circ_0000064 on the biological functions of hepatocellular carcinoma cells. The potential mechanism was explored using cell recovery experiments. In addition, the relationship between circ_0000064 and microRNA-143 was finally explored. RESULTS: QPCR results showed that the expression level of circ_0000064 in hepatocellular carcinoma tissues was remarkably higher than that of adjacent normal tissues, and the difference was statistically significant. Compared with patients with lower expression of circ_0000064, patients with higher expression of circ_0000064 exhibited remarkably higher pathological stage and lower overall survival rate. In vitro experiments demonstrated that the proliferation ability of the cells was remarkably reduced after the transfection of si-circ_0000064, while cell apoptosis ability significantly increased when compared with the NC group. Meanwhile, qPCR results indicated that microRNA-143 expression was negatively correlated with circ_0000064 expression in hepatocellular carcinoma. Luciferase reporter gene assay indicated that circ_0000064 could be targeted by microRNA-143 through their binding site. In addition, the cell recovery experiment confirmed that circ_0000064 and microRNA-143 could be mutually regulated, which affected the malignant progression of hepatocellular carcinoma together. CONCLUSIONS: Circ_0000064 level was remarkably upregulated in hepatocellular carcinoma and was associated with high pathological stage and poor prognosis of patients. In addition, circ_0000064 significantly promoted proliferation and inhibited apoptosis of hepatocellular carcinoma cells via modulating microRNA-143.

[Clinical characteristics and prognosis of overweight and obese patients with pulmonary thromboembolism].

Objective: To investigate the clinical characteristics and outcomes of overweight and obese patients with pulmonary embolism. Methods: This was a retrospective study of patients with pulmonary thromboembolism(PTE) in Beijing Hospital between 2009 and 2017. Data were analyzed and compared based on body mass index (BMI), and patients were classified into normal weight, overweight, and obese. Results: Among 372 patients with PTE, 159 were normal, 143 were overweight and 70 were obese. The mean age was (67.8±13.4) years, and 159(47.0%) were males. There was no significant difference in age, sex, smoking ratio, and underlying disease between the 3 groups (all P>0.05). Chest pain was less frequent in the obese group than the overweight group (P<0.05), and swollen of lower limbs was more prevalent in the obese group than the first 2 groups (all P<0.05). The levels of hemoglobin and hematocrit in the obese group were significantly higher than those in the normal group(P<0.05), while the serum uric acid levels were significantly higher than that in the normal group (P<0.05). Anticoagulation was more frequent in the overweight than the normal group(P<0.05) and Warfarin use was more frequent in the overweight and the obese than the normal group(both P<0.05). The mortality rate was higher in the normal group than those in the overweight and the obese groups (both P<0.01). Multiple logistic regression analysis after adjusting for age and sex showed that malignancy (OR=3.716, 95%CI: 1.733-7.972, P=0.001) and high risk PTE (OR=13.815, 95%CI: 4.093-46.624, P<0.001) were predictors of mortality, whereas anticoagulation (OR=0.155, 95%CI: 0.056-0.428, P<0.001), BMI≥24 (OR=0.142, 95%CI: 0.045-0.446, P=0.001) and BMI≥28 (OR=0.272, 95%CI: 0.085-0.872, P=0.029) were the predictors of survival. Conclusions: Proportion of hypertension, diabetes, coronary heart disease and hyperlipidemia were not significantly different in patients with overweight and obesity compared to patients with normal weight. Obese patients had higher levels of uric acid and hemoglobin than normal weight. Overweight and obese patients had a better survival.

[Clinical characteristics and outcomes of patients with lung cancer, gastrointestinal cancer and urologic cancer with venous thromboembolism].

Objective: To compare the clinical characteristics and outcomes of patients with lung cancer, gastrointestinal (GI) cancer and urologic cancer with venous thromboembolism (VTE). Methods: From January 2003 to January 2013, 192 lung cancer, GI cancer and urologic cancer patients with VTE were retrospectively evaluated for the clinical characteristics and outcomes. Results: Among 192 patients, 82 cases of lung cancer, 78 cases of GI cancer, 32 cases of urologic cancer were involved. The Eastern Cooperative oncology Group Performance Status score of GI cancer group was significantly higher than those of the lung cancer and urologic cancer groups[(2.4±1.1) vs (2.0±1.4), (1.8±1.0), both P<0.05]. The proportion of smoking patients in lung cancer group was significantly higher than that in GI cancer and urologic cancer groups (79.3% vs 30.8%, 53.1%, both P<0.05), while the proportion of operation was significantly lower than that in the latter two groups (35.4% vs 53.8%, 68.8%, both P<0.05). Pathological types of cancer were mostly adenocarcinoma, and the proportion of adenocarcinoma in lung cancer and GI cancer groups was significantly higher than that in urologic cancer group (76.9%, 73.8% vs 37.9%, both P<0.001). The proportion of moderately and/or poorly differentiated histodifferentiation in the first two groups was significantly higher than that of urologic cancer group (90.0%, 95.7% vs 40.0%, both P<0.001). The proportion of patients with TNM stage Ⅲ-Ⅳ in lung cancer group was significantly higher than that of the urological cancer group (87.0% vs 64.3%, P<0.05). The incidence of VTE in lung cancer group was significantly higher than those of GI cancer and urologic cancer groups within 6 months after tumor diagnosis, chemotherapy and operation (79.3% vs 60.3%, 46.9%; 76.5% vs 48.6%, 36.4%; 92.3% vs 57.9%, 59.1%; all P<0.05). The case fatality rate within one year in lung cancer and GI cancer groups was significantly higher than that in urologic cancer group (51.2%, 52.6% vs 18.8%, both P<0.01). The median survival time of the lung cancer and GI cancer groups was significantly shorter than that of the urological cancer group (P=0.001, 0.010, respectively). Conclusions: Adenocarcinoma, advanced cancer, and poor histodifferentiation are risk factors of VTE in cancer patients. Most events of VTE occur within 6 months after a diagnosis of cancer. The prognosis of lung cancer and GI cancer complicated with VTE is worse than that of urologic cancer with VTE.

Expression of Nrf2-Keap1-ARE signal pathway in traumatic lung injury and functional study.

OBJECTIVE: Traumatic lung injury (TLI) can cause inflammation and oxidative stress, or even leads to acute respiratory distress syndrome (ARDS) and death. Nuclear factor erythroid-2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signal pathway participates in disease occurrence and progression via regulating inflammatory and oxidative stress response, but with its expression and functional roles in TLI largely unknown. MATERIALS AND METHODS: Wistar rats were randomly divided into control group, TLI group by crushing method, and Nrf2 activation group which received Nrf2 specific agonist sulforaphane 30 min before TLI treatment. Artery blood gas (ABG), wet/dry mass ratio (W/D) of lung tissues, myeloid peroxidase (MPO) and superoxide dismutase (SOD) activity of lung tissue were analyzed. Keap1 and ARE mRNA levels were tested by Real-time PCR, while Nrf2 protein was measured by Western blot. Inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: TLI model had lower ABG or SOD, higher W/D ratio, MPO value, elevated expressions of TNF-α, IL-2, and Keap1, plus decreased Nrf2 and ARE expression (p<0.05). Nrf2 activation significantly improved ABG, decreased W/D ratio and MPO value, enhanced SOD activity, decreased TNF-α and IL-2 secretion, suppressed Keap1 expression, and facilitated Nrf2 and ARE expressions (p<0.05). CONCLUSIONS: Nrf2-Keap1-ARE signal pathway can improve TLI-related pathology via modulating oxidative stress response and suppressing inflammation.

[Analysis of correlation between spinal nerve high tension and disc degeneration in 100 cases].

Objective: To explore the correlation between the spinal nerve high tension and lumbar disc degeneration, the pathogenesis of hanging intervertebral disc degeneration. Methods: From June 2016 to June , a retrospective analysis 2017 of 100 cases of lumbar spinal stenosis were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University. They were divided into experimental group (50 cases, nerve high tension group) and control group (50 cases, nervous tension in the normal group) according to preoperative lumbar MRI of cauda equina syndrome and settlement of intraoperative detecting nerve tension. The Pfirrmann grade was used to evaluate degree of lumbar (L3/4-L5/S1) disc degeneration.The correlation between spinal nerve tension and lumbar disc degeneration was analyzed, and the severity of experimental group and control group on lumbar disc degeneration was compared. Results: There was no significant difference in the age and sex ratio between the two groups (P>0.05). The Pfirrmann score of the experimental group was L3/4 (4.74±1.6) grade, L4/5 (5.32±1.33) grade, L5/S1 (5.54±1.13) grade; the control group Pfirrmann score was L3/4 (3.5±1.16) grade, L4/5 (4.12±0.9) grade, and L5/S1 (4.1±0.97) grade.The severity of intervertebral disc degeneration in experimental group was higher than that in control group, with statistical significance (P<0.05). There was a correlation between lumbar disc degeneration and nerve tension in L3/4, L4/5 and L5/S1, and the correlation trend was L5/S1> L4/5> L3/4. Conclusion: There is a correlation between lumbar disc degeneration and spinal nerve high tension.A new pathogenesis of hanging intervertebral disc degeneration that the degeneration of lumbar disc is a compensatory mechanism in order to alleviate the axial stretch injury is put forward.

Effects of ZEB1 on regulating osteosarcoma cells via NF-κB/iNOS.

OBJECTIVE: Osteosarcoma is one common malignant bone tumors, as it frequently has invasion, metastasis and recurrence, causing unfavorable prognosis of patients. Osteosarcoma has complicated pathogenesis, which has not been elucidated fully. Therefore, the identification of effective molecular target of osteosarcoma onset can help to improve treatment efficacy and prognosis of osteosarcoma. Zinc finger E-box binding homeobox 1 (ZEB1) protein is one member of zinc finger E-box binding protein family, and participates in embryonic genesis and development. A recent study found the participation of ZEB1 in mediating multiple tumor onset and its up-regulation of osteosarcoma. The regulatory mechanism of ZEB1 in osteosarcoma has not been illustrated yet. MATERIALS AND METHODS: In vitro cultured osteosarcoma MG-63 cells were transfected with ZEB1 siRNA. Real-time PCR and Western blot were tested for ZEB1 mRNA/protein expression. MTT was used to test MG-63 cell proliferation, whilst cell invasion was used to describe the effect of ZEB1 on MG-63 cells. Caspase-3 activity assay was employed to test MG-63 cell apoptosis. Western blot was employed to detect nuclear factor kappa B (NF-kB) and inducible nitric oxide synthase (iNOS) protein expression. RESULTS: After transfecting with ZEB1 siRNA, MG-63 cell proliferation or invasion was inhibited accompanied with lower ZEB1 mRNA/protein expression. Caspase3 activity was also increased after transfection (p < 0.05), along with down-regulation of NF-kB and iNOS proteins in MG-63 cells (p < 0.05). CONCLUSIONS: Inhibition of ZEB1 can facilitate osteosarcoma cell apoptosis and inhibit cell proliferation or invasion via down-regulating NF-kB/iNOS signal pathway.

[Lumbosacral nerve bowstring disease].

Objective: To define a novel disease-lumbosacral nerve bowstring disease, and propose the diagnostic criteria, while capsule surgery was performed and evaluated in the preliminary study. Methods: From June 2016 to December 2016, a total of 30 patients (22 male and 8 female; mean age of 55.1±9.7 years) with lumbosacral nerve bowstring disease were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University.Lumbosacral nerve bowstring disease was defined as axial hypertension of nerve root and spinal cord caused by congenital anomalies, which could be accompanied by other lesions as lumbar disc herniation, spinal cord stenosis or spondylolisthesis, or aggravated by iatrogenic lesions, resulting in neurological symptoms.This phenomenon is similar to a stretched string, the higher tension on each end the louder sound.Meanwhile, the shape of lumbosacral spine looks like a bow, thus, the disease is nominated as lumbosacral nerve bowstring disease.All the patients underwent capsule surgery and filled out Owestry disability index (ODI) and Tempa scale for kinesiophobia (TSK) before and after surgery. Results: The mean surgery time was (155±36) min, (4.3±0.4) segments were performed surgery.The pre-operative VAS, TSK and ODI scores were (7.6±0.8), (52.0±10.3) and (68.4±12.7), respectively.The post-operative VAS, TSK and ODI scores were (3.3±0.4), ( 24.6±5.2) and (32.1±7.4)(P<0.05, respectively), respectively. Conclusion: The definition and diagnostic criteria of lumbosacral nerve bowstring disease was proposed.Capsule surgery was an effective strategy with most patients acquired excellent outcomes as symptoms relieved and quality of life improved.

[Comparison between poly hydroxy acrylic acid and Van-clear replacing the traditional reagents to detect the cervical hTERC genes by adopting FISH technique].

OBJECTIVE: To observe the difference of the human telomeres RNA component (hTERC) genes' amplification in the cervical tissue by applying the environment-friendly fixative poly hydroxy acrylic acid and the transparent dewaxing solution Van-clear separately or jointly to replace the traditional fixative 4% (volume fraction) neutral buffered formalin and the conventional transparent dewaxing solution xylene in the use of fluorescence in situ hybridization (FISH) for detection. METHODS: In the study, 255 cases of cervical tissue specimens submitted by the Department of Gynecology in Zhongshan Boai Hosipital were collected from Mar. 2013 to Apr. 2015. Four samples were taken from the same lesion site. All the cases were divided into 4 groups and named group A, B, C, and D. Group A used 4% neutral buffered formalin fixed and xylene dewaxing to make slices. Group B used poly hydroxy acrylic fixed and xylene dewaxing to make slices. Group C used 4% neutral buffered formalin fixed and Van-clear transparent to make slices. Group D used poly hydroxy acrylic fixed and Van-clear transparent dewaxing to make slices. The amplification of hTERC genes in the four groups of cervical specimens was also detected by FISH technique. RESULTS: When the hTERC genes were detected by FISH method under the fluorescence microscope, it was obvious that the tissue profile and the background of group A, B, C and D were all clear. The probe was fixed in the accurate position so that the bright red or green fluorescence signals were easily found in these four groups. Compared with the positive rate of group A, there was no statistical significance in that of group B, C and D (P>0.05). At the same time, the coincidence rate of the FISH results was high, which showed that the new environment-friendly reagent had no significant difference in the detection of cervical hTERC genes by FISH technique. CONCLUSION: It is possible for the environment-friendly reagent poly hydroxy acrylic acid and Van-clear to replace 4% neutral buffered formalin and xylene separately or jointly to detect the cervical hTERC genes by adopting FISH technique.

[Repeated partially reversible pulmonary arterial hypertension related to dasatinib: a case report and literature review].

OBJECTIVE: To study the clinical features and prognosis of pulmonary arterial hypertension related to dasatinib. METHODS: A case of pulmonary arterial hypertension(PAH) during dasatinib therapy was retrospectively analyzed and the related literature was reviewed. RESULTS: A 55-year-old male with chronic myelogenous leukemia was treated with dasatinib at a dosage of 100 mg/d.After 36 months of initiating the therapy, he presented with chest distress, fatigue and general edema. His heart function was graded as NHYA Ⅳ. Transthoracic Doppler echocardiography documented right ventricle enlargement, right ventricular wall thickening, reduction of right ventricular systolic function, widening of the main pulmonary artery and branches , and an estimated systolic pulmonary arterial pressure(SPAP) of 115 mmHg(1 mmHg=0.133 kPa), with pericardial effusion and normal systolic left ventricular function.Chest ultrasound documented bilateral pleural effusion.The patient had taken and withdrew dasatinib 5 times by himself.The symptom had improved after stopping the drug, with SPAP decreasing to 37-82 mmHg measured by echocardiography at the first 3 times, and the pleural effusion and the pericardial effusion had disappeared. But 1 year after the 4(th) withdrawal of the drug, his pulmonary arterial pressure had failed to decrease, and he had taken the drug again by himself. Other causes of pulmonary arterial hypertension such as lung parenchymal diseases, pulmonary thromboembolism, connective tissue diseases, other drug induced PAH, were excluded by extensive examinations. The patient refused to receive right-sided heart catheterization. The patient was followed until now. CONCLUSIONS: Dasatinib can cause partially reversible PAH. But after repeated use of the drug, PAH may become irreversible. Monitoring SPAP by transthoracic Doppler echocardiography is necessary during dasatinib therapy.