Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

Objective To construct a nomogram prediction model for the treatment effect of anlotinib with the participation of traditional Chinese medicine syndrome elements on the patients with extensive-stage small cell lung cancer (ES-SCLC) who previously received multiple lines of chemotherapy. Methods The clinical data of 127 patients with ES-SCLC who received at least two cycles of anlotinib treatment were retrospectively studied. Kaplan-Meier method was used to analyze the relationship between each factor and the overall survival time. Cox regression analysis was applied to screen the independent influencing factors of the prognosis of patients with ES-SCLC. R language was employed to build a nomogram prediction model, C-index was used to evaluate the model, and calibration curve was adopted to verify the accuracy of the model. Results Age, PS score, brain metastases, qi deficiency syndrome, yin deficiency syndrome, and blood stasis syndrome were related risk factors for ES-SCLC treated with anlotinib. PS score, brain metastasis, and blood stasis syndrome were independent prognostic factors. On the basis of these three independent influencing factors, a nomogram model was established to predict the prognosis of patients with ES-SCLC treated with anlotinib. The predicted risk was close to the actual risk, showing a high degree of coincidence. Conclusion The nomogram model established with PS score, blood stasis syndrome elements, and brain metastasis as independent factors can predict the prognosis of patients with ES-SCLC receiving second- and third-line treatment of anlotinib.

Objective:To investigate the clinical value of totally laparoscopic exclusion of splenic artery aneurysm combined with pericardial devascularization for portal hypertension com-plicated with splenic aneurysm.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 17 patients with portal hypertension complicated with splenic aneurysm who were admitted to 2 medical centers (15 cases in Shenzhen University General Hospital and 2 cases in Wuhan First Hospital) from January 2013 to May 2020 were collected. There were 7 males and 10 females, aged (59±14)years. All patients underwent totally laparoscopic exoclusion of splenic artery aneurysm combined with pericardial devascularization. Observation indicators : (1) surgical and postoperative conditions; (2) complications; (3) follow-up. Follow-up was conducted by out-patient examiantion and telephone interview to detect the effect of exclusion of arterial tumor, and blood re-flow, portal vein thrombosis and survival of patients 3 months after operation. The follow-up was up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Results:(1) Surgical and postoperative conditions. All 17 patients successfully completed the operation, without perioperative death. The operation time, volume of intraoperative blood loss of 17 patients were (181±30)minutes, 187(range, 90?420)mL. The white blood cell count, red blood cell count, hemoglobin, serum albumin were (9±4)×10 9/L, (3.5±0.9)×10 12/L, (86±17)g/L, (36±7)g/L on the postoperative day 3. Time to postoperative abdominal drainage tube removal and duration of post-operative hospital stay were (7±4)days and (11±4)days. (2) Complications. All 17 patients had ascites after surgery, which were improved after oral treatment with diuretics. There was no complication such as intra-abdominal hemorrhage, gastrointestinal fistula, pleural effusion, infection, abscess formation, fever and vascular embolism. (3) Follow-up. All the 17 patients were followed up for 28.6(range, 7.0?84.0)months. During the follow-up, the splenic aneurysm cavity of all patients was completely isolated, no blood re-flow and no portal vein thrombosis was observed, and no patient died. Conclusion:Totally laparoscopic exclusion of splenic artery aneurysm combined with pericardial devascularization is safe and feasible in the treatment of portal hypertension complicated with splenic aneurysm.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

Objective:To investigate the predictive value of thyroid stimulating hormone (TSH) levels on short-term outcome after intravenous thrombolysis in patients with acute ischemic stroke.Methods:From January 2016 to June 2019, patients with acute ischemic stroke receiving intravenous alteplase in the Department of Neurology, Jinshan Branch of Shanghai Sixth People's Hospital were enrolled retrospectively. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the degree of baseline neurological deficits. The modified Rankin Scale was used for short-term outcome evaluation at 14 d after onset. 0-2 was defined as good outcome and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factors for poor short-term outcomes. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of thyroid stimulating hormone on short-term prognosis of patients with acute ischemic stroke. Results:A total of 90 patients with acute ischemic stroke received intravenous thrombolysis were enrolled. Their age was 70.08±9.76 years, and 49 (54.44%) were male. The median NIHSS score before thrombolysis was 11.00 (interquartile range, 5.00-16.00). Forty-eight patients (53.33%) had good short-term outcomes, and 42 (46.67%) had poor short-term outcomes. Multivariate logistic regression analysis showed that after adjusting for confounding factors, severe neurological deficits at admission (severe stroke vs. mild stroke: odds ratio [ OR] 9.390, 95% confidence interval [ CI] 2.015-43.764; P=0.004) and low levels of TSH (the 2nd quartile vs. 4th quartile: OR 5.999, 95% CI 1.038-34.657, P=0.045; the 1st quartile vs.4th quartile: OR 6.525, 95% CI 1.107-38.469, P=0.038) were the independent predictors of poor short-term outcome after intravenous thrombolysis in patients with acute ischemic stroke. The ROC curve analysis showed that the area under the curve of TSH for predicting poor outcomes was 0.682 (95% CI 0.572-0.793; P=0.003). The best cutoff value was 1.695 mIU/L, the sensitivity was 76.19%, and the specificity was 60.42%. Conclusion:The decreased serum TSH is an independent predictor of poor short-term outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Objective:To explore the relationship between cardiac radiation dose and prognosis of patients with non-small cell lung cancer (NSCLC).Methods:From August 2015 to September 2018, the clinical data and cardiac dose parameters of 180 patients with locally advanced NSCLC who received radiotherapy in Tangshan people′s Hospital of Hebei Province were analyzed retrospectively.The relationship between cardiac dose parameters and overall survival rate was analyzed by K-M analysis, and the prognostic factors of NSCLC patients were identified by multivariate Cox regression.Results:The median survival time of NSCLC patients was 33.4 months.Univariate analysis indicated prescription dose≥56Gy ( HR 1.54, 95% CI1.28-2.86, P=0.011), hypertension ( HR 1.42, 95% CI1.34-1.89, P=0.012), mean cardiac dose≥13.9Gy ( HR 1.12, 95% CI1.05-2.61, P=0.031), V5≥70% ( HR 1.08, 95% CI1.01-2.16, P=0.044), and V30≥40% ( HR 1.16, 95% CI1.04-3.01, P=0.041), V50≥20% ( HR 1.23, 95% CI1.11-2.81, P<0.001), and V60≥5% ( HR 1.03, 95% CI1.00-1.89, P=0.037) were the prognostic factors of NSCLC patients.After multi-factor adjustments, receiving chemotherapy was a favorable factor for the prognosis of NSCLC patients ( HR 0.711, 95% CI0.35-0.89, P=0.005); hypertension was a factor of poor prognosis ( HR 1.641, 95% CI1.56-1.86, P=0.034); V50≥20% in cardiac dose ( HR 1.161, 95% CI1.13-3.82, P=0.002) was a poor prognostic factor in NSCLC patients. Conclusion:The cardiac dose V50 is an independent predictor of prognosis in patients with advanced NSCLC.The increase of cardiac radiation dose may increase the potential risk of death.In clinical practice, the prognosis of patients may be improved by reducing the cardiac radiation dose.

Aim To observe the neuroprotective effect of sinomenine on hippocampal neurons from injury in-duced by oxygen glucose deprivation ( OGD ) and its underlying mechanism. Methods Hippocampal neu-rons were exposed to OGD for 4 h followed by 24 h re-oxygenation ( OGD-R) . Then cell viability was detec-ted by MTT. LDH release was detected by LDH kit. Cell apoptosis was detected by Hoechst stain. The ex-pression of Bax, Bcl-2 and caspase-3 were detected by Western blot. [ Ca2+] i of hippocampal neurons was detected by calcium imaging. Acid-sensing ion chan-nels ( ASICs ) current was detected by patch clamp technique. Results SN increased cell viability and reduced LDH release. SN also inhibited neuron apop-tosis and increased ratio of Bcl-2/Bax and reduced the expression of caspase-3 . OGD-induced increase of [ Ca2+] i was inhibited by SN. Furthermore, SN inhib-ited ASIC1 a current and also inhibited OGD induced increase of ASICs current in hippocampal neurons. Conclusion SN protects hippocampal neurons against OGD-R-induced injury. The inhibitory effect of SN on ASIC1 a and calcium overload was involved in the pro-tective effect of SN.

Objective To evaluate the role of thoracic three-dimensional conformal radiotherapy (3DCRT) in patients with extensive-stage small cell lung cancer (ES-SCLC).Methods A total of 171 patients with ES-SCLC admitted from 2004 to 2009 were included in the study.Eighty-six patients received thoracic 3DCRT and systemic chemotherapy (CT),while 85 patients received systemic CT alone.3DCRT was delivered at 1.5 Gy/fraction twice daily or 2.0 Gy/fraction once daily,with a total dose ranging from 40 to 62 Gy.The CT regimen consisted of carboplatin/cisplatin and etoposide.The survival time and survival rate were calculated by the Kaplan-Meier method,and the log-rank test was used for univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％.The median overall survival (OS) time and the 2-and 5-year OS rates were 15 months,31.5％,and 2.4％,respectively,for all patients;they were 18 months,35.3％,and 2.4％,respectively,for the CT/3DCRT group,versus 12 months,14.5％,and 2.4％ for the CT group (P =0.023).The median progression-free survival (PFS) time and the 1-and 2-year PFS rates were 8 months,27.5％,and 2.4％,respectively,for all patients;they were 9 months,35.4％,and 6.0％,respectively,for the CT/3DCRT group,versus 6 months,20.5％,and 6.0％ for the CT group (P =0.004).In the CT/3DCRT group,the 22 patients who received 45 Gy at 1.5 Gy/fraction twice daily had a median PFS time of 11 months,versus 9 months for the 26 patients who received 60 Gy at 2.0 Gy/fraction once daily (P =0.037).Multivariate analysis revealed that receiving ≥ 4 cycles of CT (P =0.001) and 3DCRT (P =0.008) were favorable prognostic factors for OS.Conclusions Thoracic 3DCRT can improve the OS and PFS in patients with EDSCLC,and it has good efficacy when delivered with a total dose of 45 Gy at 1.5 Gy/fraction twice daily.Thoracic 3DCRT and receiving ≥4 cycles of CT are independent favorable prognostic factors for OS.

It is well established that neural stem cells (NSCs) are not randomly distributed throughout the brain, but rather are concentrated around blood vessels. Although NSCs lie in a vascular niche, there is no direct evidence for a functional relationship between the NSCs and blood vessel component cells. It is reported that endothelial cells release soluble factors that stimulate the self-renewal of NSCs, inhibit their differentiation, and enhance their neuron production. Endothelial coculture can activate Notch to promote self-renewal. Furthermore, vascular endothelial growth factor (VEGF) plays a significant role in neural cells; it stimulates the growth and differentiation of astrocytes in the central nervous system (CNS). Therefore, beyond their traditional role as structural components of blood vessels, endothelial cells are not only critical component of the neural stem cell niche, but they also are able to enhance neurogenesis, possibly through the secretion of brain-derived neurotrophic factor.
Brain-Derived Neurotrophic Factor ; secretion ; Cell Differentiation ; physiology ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Endothelial Cells ; cytology ; physiology ; Humans ; Neurons ; cytology ; Stem Cells ; cytology ; Vascular Endothelial Growth Factor A ; physiology

BACKGROUND: Total flavone of ginkgo biloba(TFG) can affect on free radical, but the effect on apoptosis induced by cerebral ischemia is unclear.OBJECTIVE: To study the inhibitory effect of TFG on apoptosis induced by cerebral ischemia.DESIGN: Completely randomized controlled experimental study based on experimental animals.SETTING: Department of pharmacology in a university.MATERIALS: Totally 24 SD rats in half genders with clean grade and body mass of(250 ± 50) g, were divided into 4 groups at random: sham-operation group, model group, TFG 40 rmg/kg group and TFG 80 mg/kg group (Certificate No. 01).METHODS: This study was completed in the Department of Pharmacology,Anhui Medical University during October 2001 and January 2002. Incomplete cerebral ischemia was made by ligating bilateral common carotid arteries(CCA) in rats. The cerebral injury was evaluated by brain edema. The apoptosis was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling(TUNEL) and transmission electron microscopy (TEM) method. The DNA fragmentation analysis was measured with the diphenylamine reagent method.MAIN OUTCOME MEASURES: Major factor: Effect of TFG on ultrastructral alteration of apoptotic cerebral cortex cells; Secondary factor: Effect of TFG on DNA fragmentation induced by cerebral ischemia.RESULTS: Ligating of bilateral CCA markedly induced apoptotic cell in cerebral cortex. TFG 80 mg/kg significantly inhibited brain edema( P ＜ 0.05 )and decreased the numbers of apoptotic cells in cortex( P ＜ 0.01 ) and improved ultrastructral alteration of apoptotic cells; TFG 40, 80 rmg/kg also inhibited the increase of DNA fragmentation induced by cerebral ischemia (P ＜0.05, P ＜0.01).CONCLUSION: TFG has inhibitory effect on ischemia-induced apoptosis of cerebral cortex and improve the ultrastructual changes of apoptosis. Moreover,TFG can relieve the occurrence of edema of ischemic brain tissue and inhibit the increase of DNA section induced by cerebral ischemia.