Objective To use a physics-informed neural network(PINN)-based model to predict hemodynamics in intracranial aneurysms and address the problems of long simulation time and high computational cost in traditional computational fluid dynamics(CFD)simulations.Methods The PINN model was trained using only the computational domain coordinates and sparse velocity measurement points from CFD data of clinical patients.The predicted blood flow velocity,pressure,and wall shear stress(WSS)from the PINN model were compared with CFD simulation results.Results The proposed method was used to test and validate data from four different patients.For velocity prediction,the average mean absolute error(MAE),average mean relative error(MRE),average mean squared error(MSE)was 4.60％,6.61％,and 0.229％,respectively.For WSS prediction,the average MAE,MRE and MSE was 5.54％,8.58％,and 0.510％,respectively.The PINN model demonstrated a good generalization capability across different aneurysm models and could reduce the computation time of hemodynamics from several hours to just a few seconds.Conclusions The PINN model can effectively compensate for incomplete measurement data through physical constraints,even when boundary conditions are unknown and measurement data are sparse.It can rapidly and accurately simulate the hemodynamics of intracranial aneurysms.This method has the potential to provide effective support for clinical risk prediction in intracranial aneurysms.

Objective To use a physics-informed neural network(PINN)-based model to predict hemodynamics in intracranial aneurysms and address the problems of long simulation time and high computational cost in traditional computational fluid dynamics(CFD)simulations.Methods The PINN model was trained using only the computational domain coordinates and sparse velocity measurement points from CFD data of clinical patients.The predicted blood flow velocity,pressure,and wall shear stress(WSS)from the PINN model were compared with CFD simulation results.Results The proposed method was used to test and validate data from four different patients.For velocity prediction,the average mean absolute error(MAE),average mean relative error(MRE),average mean squared error(MSE)was 4.60％,6.61％,and 0.229％,respectively.For WSS prediction,the average MAE,MRE and MSE was 5.54％,8.58％,and 0.510％,respectively.The PINN model demonstrated a good generalization capability across different aneurysm models and could reduce the computation time of hemodynamics from several hours to just a few seconds.Conclusions The PINN model can effectively compensate for incomplete measurement data through physical constraints,even when boundary conditions are unknown and measurement data are sparse.It can rapidly and accurately simulate the hemodynamics of intracranial aneurysms.This method has the potential to provide effective support for clinical risk prediction in intracranial aneurysms.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved ¹O₂ generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Objective:To investigate the relationship between red blood cell distribution width (RDW) and activity of Crohn′s disease (CD), and explore the diagnostic value of RDW for CD activity.Methods:A cross-sectional study was conducted. Clinical data of CD patients treated continuously at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2012 to October 2014 (CD group) were collected, including the first results of routine hematological examinations and C-reactive protein (CRP) levels after admission. Routine hematological examination results were also collected from healthy peoples undergoing regular health check-ups at the same time, who served as the normal control group. CD patients were divided into remission, mild activity, and moderate-severe activity groups based on the Crohn′s disease activity index (CDAI). The levels of routine hematological indicators including RDW and platelet-to-lymphocyte ratio (PLR) were compared between the CD group and the normal control group, as well as among different subgroups of CD patients. The correlations between RDW, PLR and CD activity or CRP were analyzed, and the diagnostic value of RDW for CD activity was evaluated by using ROC curve. Logistic univariate and multivariate regressions were performed to analyze the influencing factors of the activity of CD. Logistic regression equation was constructed to calculate the diagnostic efficacy of the influencing factors.Results:A total of 303 CD patients (216 males, 87 females; mean age 28.6 ± 11.7 years) were assigned to CD group and 293 healthy peoples (190 males, 103 females; mean age 30.1 ± 12.3 years) were assigned to normal control group. There was no significant differences in age and gender between the two groups (both P>0.05), indicating comparability. Among the CD patients, 109 were in remission group, 106 in mild activity group, and 88 in moderate-severe activity group. There was no significant differences in age and gender among the three subgroups (all P>0.05), indicating comparability. Compared with the normal control group, RDW (15.26% ± 2.51% vs. 13.10% ± 1.13%, P<0.001), PLR (245.09 ± 158.69 vs. 119.07 ± 36.52, P<0.001), neutrophil-to-lymphocyte ratio (NLR) [3.22 (2.06, 4.75) vs. 1.76 (1.39, 2.32), P<0.001], white blood cell count [ (7.68 ± 3.30) ×10 9/L vs. (6.52 ± 1.68) × 10 9/L, P<0.001] and platelet count [ (320.69 ± 116.10) × 10 12/L vs. (230.10 ± 51.08) × 10 12/L, P<0.001] were significantly higher in the CD group, while hemoglobin [ (112.8 ± 21.0) g/L vs. (137.1 ± 13.5) g/L, P<0.001] and platelet distribution width (PDW) [ (10.70 ± 1.91) fl vs. (11.89 ± 1.75) fl, P<0.001] were significantly lower. Compared with patients in remission group, the patients in mild activity group had higher RDW and platelet count, and lower hemoglobin (all P<0.05). Compared with the patients in remission and mild activity groups, the patients in moderate-severe activity group had higher RDW, PLR and NLR, and lower hemoglobin (all P<0.05). Correlation analysis showed the positive correlations between RDW, PLR and CD activity ( r = 0.423, P<0.001; r = 0.295, P<0.001), and RDW was positively correlated with CRP ( r = 0.438, P<0.001). The cut-off value of RDW for predicting CD activity was 13.85%, while the area under curve (AUC) was 0.723 (95% CI: 0.664-0.782, P<0.001), sensitivity was 0.784 and specificity was 0.550. Logistic multivariable regression analysis showed that RDW ( OR = 1.532, 95% CI: 1.291-1.818, P<0.001) and PLR ( OR = 1.003, 95% CI: 1.001-1.006, P = 0.013) were independent risk factors. The combination of RDW and PLR in diagnosing CD activity yielded an AUC of 0.730 (95% CI: 0.673-0.787, P<0.001), sensitivity of 0.407, and specificity of 0.927. Conclusions:CD patients with high RDW have more severe activity. RDW is a simple and practical indicator for diagnosing the activity of CD.

Objective:To investigate the relationship between red blood cell distribution width (RDW) and activity of Crohn′s disease (CD), and explore the diagnostic value of RDW for CD activity.Methods:A cross-sectional study was conducted. Clinical data of CD patients treated continuously at the Sixth Affiliated Hospital of Sun Yat-sen University from November 2012 to October 2014 (CD group) were collected, including the first results of routine hematological examinations and C-reactive protein (CRP) levels after admission. Routine hematological examination results were also collected from healthy peoples undergoing regular health check-ups at the same time, who served as the normal control group. CD patients were divided into remission, mild activity, and moderate-severe activity groups based on the Crohn′s disease activity index (CDAI). The levels of routine hematological indicators including RDW and platelet-to-lymphocyte ratio (PLR) were compared between the CD group and the normal control group, as well as among different subgroups of CD patients. The correlations between RDW, PLR and CD activity or CRP were analyzed, and the diagnostic value of RDW for CD activity was evaluated by using ROC curve. Logistic univariate and multivariate regressions were performed to analyze the influencing factors of the activity of CD. Logistic regression equation was constructed to calculate the diagnostic efficacy of the influencing factors.Results:A total of 303 CD patients (216 males, 87 females; mean age 28.6 ± 11.7 years) were assigned to CD group and 293 healthy peoples (190 males, 103 females; mean age 30.1 ± 12.3 years) were assigned to normal control group. There was no significant differences in age and gender between the two groups (both P>0.05), indicating comparability. Among the CD patients, 109 were in remission group, 106 in mild activity group, and 88 in moderate-severe activity group. There was no significant differences in age and gender among the three subgroups (all P>0.05), indicating comparability. Compared with the normal control group, RDW (15.26% ± 2.51% vs. 13.10% ± 1.13%, P<0.001), PLR (245.09 ± 158.69 vs. 119.07 ± 36.52, P<0.001), neutrophil-to-lymphocyte ratio (NLR) [3.22 (2.06, 4.75) vs. 1.76 (1.39, 2.32), P<0.001], white blood cell count [ (7.68 ± 3.30) ×10 9/L vs. (6.52 ± 1.68) × 10 9/L, P<0.001] and platelet count [ (320.69 ± 116.10) × 10 12/L vs. (230.10 ± 51.08) × 10 12/L, P<0.001] were significantly higher in the CD group, while hemoglobin [ (112.8 ± 21.0) g/L vs. (137.1 ± 13.5) g/L, P<0.001] and platelet distribution width (PDW) [ (10.70 ± 1.91) fl vs. (11.89 ± 1.75) fl, P<0.001] were significantly lower. Compared with patients in remission group, the patients in mild activity group had higher RDW and platelet count, and lower hemoglobin (all P<0.05). Compared with the patients in remission and mild activity groups, the patients in moderate-severe activity group had higher RDW, PLR and NLR, and lower hemoglobin (all P<0.05). Correlation analysis showed the positive correlations between RDW, PLR and CD activity ( r = 0.423, P<0.001; r = 0.295, P<0.001), and RDW was positively correlated with CRP ( r = 0.438, P<0.001). The cut-off value of RDW for predicting CD activity was 13.85%, while the area under curve (AUC) was 0.723 (95% CI: 0.664-0.782, P<0.001), sensitivity was 0.784 and specificity was 0.550. Logistic multivariable regression analysis showed that RDW ( OR = 1.532, 95% CI: 1.291-1.818, P<0.001) and PLR ( OR = 1.003, 95% CI: 1.001-1.006, P = 0.013) were independent risk factors. The combination of RDW and PLR in diagnosing CD activity yielded an AUC of 0.730 (95% CI: 0.673-0.787, P<0.001), sensitivity of 0.407, and specificity of 0.927. Conclusions:CD patients with high RDW have more severe activity. RDW is a simple and practical indicator for diagnosing the activity of CD.

Objective:To investigate the effects of docetaxel for postoperative chemotherapy of advanced gastric cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 311 patients with advanced gastric cancer who were admitted to Lanzhou University Second Hospital from January 2013 to December 2018 were collected. There were 224 males and 87 females, aged from 26 to 82 years, with a median age of 58 years. Of 311 patients, 204 cases undergoing chemotherapy with the FOLFOX regimen (oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FOLFOX group, and 107 cases undergoing chemotherapy with the FLOT regimen (docetaxel, oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FLOT group. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups of patients after matching; (2) follow-up; (3) analysis of survival factors; (4) subgroup analysis; (5) adverse reactions. Follow-up was performed using a combination of outpatient examination, hospitalization review and telephone interview to detect situations of patients chemotherapy, postoperative survival, tumor recurrence and metastasis up to February 2019. The propensity score matching was realized using the nearest neighbor method with 1: 1 ratio and caliper setting as 0.02. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability method. Rank data was analyzed using non parametric Rank sum test. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method. The survival analysis was done using the Log-rank test. Univariate analysis and multivariate analysis were conducted using the COX regression model. Subgroup analysis was done using interaction test. Results:(1) The propensity score matching conditions and comparison of general data between the two groups of patients after matching: 198 of 311 patients had successful matching, including 99 in each group. Cases with tumor differentiated as poorly differentiation or well differentiation, cases with CA19-9 <27 U/mL or ≥27 U/mL, cases with CA125 <35 U/mL or ≥35 U/mL before propensity score matching were 109, 95, 156, 48, 186, 18 in the FOLFOX group, and 42, 65, 93, 14, 104, 3 in the FLOT group, respectively, showing significant differences in the above indicators between the two groups ( χ2=5.649, 4.798, 4.039, P<0.05). After propensity score matching, the above indicators were 44, 55, 85, 14, 96, 3 in the FOLFOX group, and 42, 57, 85, 14, 96, 3 in the FLOT group, respectively, showing no significant difference in the above indicators between the two groups ( χ2=0.082, 0.000, 0.000, P>0.05). (2) Follow-up: 198 patients of the two groups after matching were followed up for 2 to 69 months, with a median follow-up time of 38 months. During the follow-up, 92 cases survived without tumor, 2 cases underwent tumor recurrence or metastasis, and 104 cases died including 103 with tumor related death and 1 case with non-tumor related death. The courses of chemotherapy were 5.6±0.7 and 5.4±0.8 for the FOLFOX group and FLOT group, respectively, showing no significant difference between the two groups ( t=1.651, P>0.05). The 1, 3, and 5-year cumulative survival rates of patients were 72.2%, 31.5%, 27.7% and 83.2%, 42.8%, 38.2% for the FOLFOX group and FLOT group, respectively. The median overall survival time were 21 months and 34 months for the FOLFOX group and FLOT group, respectively, showing significant difference between the two groups ( χ2=4.473, P<0.05). (3) Analysis of survival factors: results of univariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with tumor as diffuse type of Lauren classification, cases with tumor as mixed type of Lauren classification, cases with tumor differentiated as well differentiation, cases with tumor diameter≥5 cm, cases with CA19-9≥27 U/mL, cases with carcinoembryonic antigen (CEA)≥3.4 μg/L, cases with tumor as T4 stage of T staging, cases with tumor as N2 stage of N staging, cases with tumor as N3 stage of N staging, cases undergoing distal gastrectomy and cases undergoing total gastrectomy were related factors influencing postoperative survival of patients ( hazard ratio=0.659, 1.617, 1.798, 0.672, 1.726, 1.655, 1.942, 2.036, 2.536, 4.085, 1.810, 2.310, 95% confidence interval: 0.444-0.978, 1.024-2.556, 1.105-2.926, 0.457-0.990, 1.159-2.569, 1.006-2.723, 1.295-2.912, 1.190-3.484, 1.409-4.564, 2.491-6.697, 1.020-3.211, 1.261-4.233, P<0.05). Results of multivariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with CEA≥3.4 μg/L, cases with tumor as N2 stage of N staging and cases with tumor as N3 stage of N staging were independent risk factors influencing postoperative survival of patients ( hazard ratio=0.622, 1.732, 2.217, 4.039, 95% confidence interval: 0.418-0.926, 1.124-2.670, 1.200-4.097, 2.448-6.662, P<0.05). (4) Subgroup analysis: results of subgroup analysis showed that of the different subgroups using gender, age, tumor Lauren classification, tumor differentiation degree, tumor location, tumor diameter, tumor markers, tumor T staging, tumor N staging and surgical procedures as subgrouping index, the efficacy difference between the FLOT group and the FOLFOX group was the same (interaction P>0.05). (5) Adverse reactions: the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia, anemia, thrombocytopenia, nausea, vomiting and liver and kidney dysfunction were 11.1%(11/99), 2.0%(2/99), 3.0%(3/99), 12.1%(12/99), 4.0%(4/99), 1.0%(1/99) and 34.3%(34/99), 1.0%(1/99), 9.1%(9/99), 24.2%(24/99), 4.0%(4/99), 0 in the FOLFOX group and the FLOT group, respectively. There were significant differences of the incidence of leukopenia and nausea between the two groups ( χ2=15.213, 4.889, P<0.05). There was no significant difference of the incidence of thrombocytopenia between the two groups ( χ2=3.194, P>0.05) and there was no significant difference of the incidence of anemia, vomiting and liver and kidney dysfunction between the two groups ( P>0.05). There was no patient in the two group withdrawal from chemotherapy as no tolerance to toxic reactions. All patients were treated with glucocorticoids, proton pump inhibitors and serotonin receptor antagonists during chemotherapy. Patients undergoing leukopenia were treated with granulocyte stimulating factor. Conclusions:Compared with FOLFOX regimen, FLOT regimen which adds docetaxel significantly prolongs the postoperative median overall survival time of patients with advanced gastric cancer. However, FLOT regimen increases the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia and nausea.

Objective To observe the evolution of astrocytes,GDNF,BDNF and Jak-STAT signal pathway after spinal cord ischemia-reperfusion injury in rabbits.Methods Spinal cord ischemia was induced by means of balloon occlusion of the infrarenal aorta for 22 minutes in 54 male New Zealand white rabbits.We assigned rabbits to 9 groups (n =6),one sham group,eight operation groups.The operation process in the sham group was the same as the operation group except the ischemia reperfusion of the spinal cord.At 0 h,1 h,2 h,3 h,8 h,24 h,48 h and 72 h after reperfusion,animals were sarcrificed and the spinal cord was removed for histologic,immunohistochemical study and western blotting.Results Normal neurons were decreased with the extension of reperfusion time.Levels of GFAP increased at 3 h and reached a peak at 48 h after reperfusion.GDNF was increased reaching two peaks after injury,the first peak was at 3 h,the second was at 72 h.BDNF level was increased and peaked at 24 h after reperfusion.The expression of p-STAT3 showed a biphasic pattern which peaked at 1h and 48 h.GFAP,GDNF,BDNF were rare and the level of p-STAT3 could be neglected in sham group.Conclusion Spinal cord ischemia-reperfusion injury could induce the activation of astrocytes,the expression of GDNF,BDNF and the activation of JakSTAT signal pathway.They showed different expression rules in this study.

Objective: To observe the activation of microglia and the changing rule of inflammatory cytokine as IL-6, IL-10 and nuclear factor-κB (NF-κB) in experimental rabbits after spinal cord ischemia reperfusion (SCIR) injury in order to provide theoretical basis for post-conditioning time. Methods: Rabbit SCIR injury model was established by thoracic aorta balloon occlusion. 54 New Zealand male adult white rabbits were divided into 9 groups: Sham group (the animals received balloon implantation without occlusion), SCIR-0h group (reperfusion was conducted at 0 hour of spinal cord ischemia), SCIR-1h, -2h, -3h, -8h, -24h,-48h and -72h groups. n=6 in each group. The number of normal and apoptosis neurons, the levels of Iba-1, IL-6, IL-10 and NF-κB in spinal tissue were examined and compared among different groups respectively. Results: The number of normal neuron was decreasing with the extended reperfusion time, TUNEL-positive neuron began to increasing in SCIR-8h group and the peak was reached in SCIR-24h group. The expression of Iba-1 began to elevating in SCIR-2h group and the peak was obtained in SCIR-8h group; NF-κB began to rising in SCIR-3h group and the peak was observed in SCIR-8h group; both IL-6 and IL-10 arrived the peak in SCIR-24h group. The expressions of NF-κB, IL-6 and IL-10 were positively related to Iba-1 level. Conclusion: Microglia activation had dynamic changes in experimental SCIR rabbits and the expression levels of NF-κB, IL-6 and IL-10 were positively to microglia activation; post-conditioning time at front and back to microglia activation may reduce neuron injury.

Objective To explore the mechanism underlying the poor prognosis in cerebral infarction (CI) patients with low T3 syndrome by comparing the NIHSS scores in these patients with or without low T3 syndrome.Methods One hundred and sixty-two patients with CI,admitted to our hospital from January 2010 to December 2012,were chosen in our study; the levels of thyroid hormones,including triiodothyronine (T3),four iodine thyronine (T4),thyroid stimulating hormone (TSH),free Triiodothyronine (iT3) and free four iodine thyronine (fT4),were measured by radioimmunoassay.CI lesions and TOAST distribution were determined by cranial MRI,magnetic resonance angiography (MRA) or CT angiography (CTA),and carotid ultrasonography.NIHSS scores at the worst in cerebral infarction inpatients were detected.Results In the 162 patients with CI,29 patients (17.90％) were combined with low T3 symptom and 20 had fT3 level lower than the lowest normal level (2.63 pmol/L); and T4,fT4 and TSH levels were within normal limits.T3,fr3 and TSH levels in patients with low T3 symptom were significantly lower than those of patients without low T3 symptom (P＜0.05).The distribution of TOAST showed no significant difference between patients with low T3 symptom and patients without low T3 symptom (P＞0.05).In patients with large artery atherosclerosis-internal carotid artery,the NIHSS scores at the worst in patients with low T3 level were significantly higher as compared with those in patients with normal T3 levels (P＜0.05).Conclusion The neurologic impairment is more severe in large artery atherosclerosis-intemal carotid artery patients with low T3 level than those without low T3 level,which might be responsible for the poor prognosis of the illness with low T3 syndrome.

ObjectiveThis study is aimed to investigate the association of human leukocyte antigen (HLA)-DRB1 with rheumatoid arthritis (RA) in Chinese Han population.MethodsA total of 281 Chinese Han patients with RA and 202 healthy controls were recruited.DNA was extracted from PBMC and HLA typing was performed by sequence based typing and PCR-Sequence Specific Primer.The frequency of HLADRB1 was compared between patients and controls using x2 test with continuity correction.ResultsThe susceptible HLA-DRB1 alleles were * 0101,* 0102,*0404,* 0405,and * 0410 which belonged to QRRAA.DRRAA and DERAA were protective alleles.At genotypic level,The association of S3P and S3D was detected.However,the protective effect of S3D was shown to be in a recessive mode.ConclusionOur results have shown that there are racial differences in RA susceptibility between Chinese Han population and Caucasians.