Objective:To investigate the relationship between thyroid function abnormality-immune related adverse event (TFA-irAE) and treatment efficacy and survival in advanced cancer patients treated with programmed death-1 (PD-1) inhibitors.Methods:The clinical data of 90 patients with advanced cancer who received 6 cycles of PD-1 inhibitor treatment from January 2021 to June 2022 in Department of Oncology of Yuncheng Central Hospital Affiliated to Shanxi Medical University were collected. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured by chemiluminescence immunoassay in patients after PD-1 inhibitor treatment, and the incidence of TFA-irAE was observed in the patients after 6 cycles of therapy. According to the occurrence of TFA-irAE, the patients were divided into TFA-irAE occurrence group ( n=40) and TFA-irAE non-occurrence group ( n=50), the therapeutic efficacy and survival of the two groups were calculated and compared. The thyroid function indexes of patients with different efficacy (33 cases in effective group and 57 cases in ineffective group) and patients with different prognosis (30 cases in survival group, 60 cases in death group) were compared, and the influencing factors of efficacy and survival were analyzed by multivariate logistic regression and Cox analysis. Kaplan-Meier survival curve was drawn, and the survival of TFA-irAE occurrence group and TFA-irAE non-occurrence group were compared by log-rank test. Results:One year after treatment, the treatment effective rate of TFA-irAE occurrence group and TFA-irAE non-occurrence group were 42.5% (17/40), 32.0% (16/50), respectively, with no statistically significant difference ( χ2=1.06, P=0.304). After 6 cycles of PD-1 inhibitor treatment, serum levels of TSH [ (2.56±0.41) mU/ml vs. (3.11±0.53) mU/ml], TPOAb [ (56.78±5.72) U/ml vs. (62.67±6.31) U/ml] and TGAb [ (81.57±8.23) U/ml vs. (92.34±9.31) U/ml] in the effective group were significantly lower than those in the ineffective group, with statistically significant differences ( t=4.45, P<0.001; t=3.89, P<0.001; t=5.29, P<0.001). The serum levels of TSH [ (2.69±0.46) mU/ml vs. (3.06±0.65) mU/ml], FT 4 [ (10.45±1.13) pmol/L vs. (11.50±1.36) pmol/L], TPOAb [ (56.27±5.61) U/ml vs. (62.47±6.34) U/ml] and TGAb [ (81.62±8.31) U/ml vs. (91.73±9.35) U/ml] in the survival group were significantly lower than those in the death group, with statistically significant differences ( t=2.27, P=0.025; t=3.02, P=0.003; t=3.79, P<0.001; t=4.19, P<0.001). Multivariate logistic regression analysis showed that TSH ( OR=1.52, 95% CI: 1.13-2.05, P=0.006), TPOAb ( OR=1.42, 95% CI: 1.13-1.78, P=0.002) and TGAb ( OR=1.35, 95% CI: 1.05-1.73, P=0.018) were all independent factors affecting the efficacy of patients with advanced cancer treated with PD-1 inhibitors. Multivariate Cox regression analysis showed that TSH ( HR=1.42, 95% CI: 1.06-1.92, P=0.030), TPOAb ( HR=1.31, 95% CI: 1.05-1.64, P=0.018), TGAb ( HR=1.41, 95% CI: 1.09-1.83, P=0.008) and FT 4 ( HR=1.36, 95% CI: 1.02-1.81, P=0.038) were all independent factors affecting the survival of patients with advanced cancer treated with PD-1 inhibitors. Survival analysis showed that the median overall survival in the TFA-irAE occurrence group and the TFA-irAE non-occurrence group were 10.8 and 8.0 months, respectively, with a statistically significant difference ( χ2=9.53, P=0.002) . Conclusion:Although the occurrence of TFA-irAE may have less effect on the efficacy of advanced tumor patients treated with PD-1 inhibitors, it may affect the survival of patients. TSH, TPOAb and TGAb are all independent influencing factors for the efficacy of patients with advanced tumors treated with PD-1 inhibitors, while TSH, TPOAb, TGAb and FT 4 are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objective To develop an intelligent recognition model based on deep learning algorithms of unmanned aerial vehicle (UAV) images, and to preliminarily explore the value of this model for remote identification, monitoring and management of cattle, a source of Schistosoma japonicum infection. Methods Oncomelania hupensis snail-infested marshlands around the Poyang Lake area were selected as the study area. Image datasets of the study area were captured by aerial photography with UAV and subjected to augmentation. Cattle in the sample database were annotated with the annotation software VGG Image Annotator to create the morphological recognition labels for cattle. A model was created for intelligent recognition of livestock based on deep learning-based Mask R-convolutional neural network (CNN) algorithms. The performance of the model for cattle recognition was evaluated with accuracy, precision, recall, F1 score and mean precision. Results A total of 200 original UAV images were obtained, and 410 images were yielded following data augmentation. A total of 2 860 training samples of cattle recognition were labeled. The created deep learning-based Mask R-CNN model converged following 200 iterations, with an accuracy of 88.01%, precision of 92.33%, recall of 94.06%, F1 score of 93.19%, and mean precision of 92.27%, and the model was effective to detect and segment the morphological features of cattle. Conclusion The deep learning-based Mask R-CNN model is highly accurate for recognition of cattle based on UAV images, which is feasible for remote intelligent recognition, monitoring, and management of the source of S. japonicum infection.

[Abstract] Chemokines are small secreted proteins produced by cancer and stromal cells. Chemokine receptors are also expressed on the surface of tumor cells and stromal cells. Chemokines bind to their homologous receptors to regulate tumor growth directly and indirectly, including direct regulation of tumor proliferation and metastasis by activating signal pathway, indirect regulation of tumor through acting on vascular endothelial cells and regulating immune response by coordinating the migration and localization of immune cells in tissues. Chemokines can be divided into four categories: CXC, CC, CX3C and C, among which CXC and CC are the most studied subtypes. In view of the fact that CXC chemokines and their receptors play a wide range of roles in malignant tumors and are closely related to the immune system, they are expected to become potential therapeutic targets, to improve tumor immune response by combining with immune checkpoint inhibitors to act in tumor microenvironment (TME). This paper reviews the research progress on chemokine/chemokine receptor axis of CXC subtypes, including the basic biological characteristics of tumor-promoting axis CXCR2/CXCLs, CXCR4/CXCL12 and tumor-suppressing axis CXCR3/CXCL9-11, their direct effect on tumor, indirect effect on TME, targeted therapy and prognostic significance of the receptors and ligands contained in these three axes.

Objective:To investigate the induction of specific T lymphocyte by bispecific monoclonal antibody in pancreatic cancer and its killing effects on KIF20A positive pancreatic cancer PANC1 cell line.Methods:CD 3/KIF20A bispecific monoclonal antibody was prepared and concentrated by chemical cross-linking method and purified by Sephrose-25 gel chromatography. Peripheral blood samples of healthy volunteers were collected, and monocytes were isolated using lymphocyte separation solution, and then cultured as dendritic cells (DC) and T cells respectively, and then co-cultured as DC-T cells. Meanwhile vitamin C was used to treat DC-T cells (vcDC-T cells). The levels of IFN-γ, IL-2, IL-4 and IL-12 in the supernatants and T cell subsets were detected by flow cytometry. About 1×10 5 T cells, DC-T cells, and vcDC-T cells with 10, 50, 100 and 300 ng CD 3/KIF20A antibody loaded were cocultured with PANC1 cells (20∶1) for 2, 6 and 10 hours to determine the highest killing rate dosage of CD 3/KIF20A antibody loaded cells. DC-T cells and DC-T cells, vcDC-T cells loaded with the highest killing rate dosage of CD 3/KIF20A antibody were cocultured with PANC1 cells (20∶1) for 2, 6, 8, 10 and 12 hours. The aggregation effect of effector cells on target cells was observed under inverted microscope, the killing rate of tumor cells was detected by LDH method. Results:The molecular weight of CD 3/KIF20A antibody was 130 000 measured and validated by SDS gel electrophoresis. The ratio of CD 8+ CD 28+ and CD40L subsets of vcDC-T cells was increased [(47.6±15.8)% vs (38.2±7.6)%, (52.1±4.9)% vs (44.7±3.2)% ] compared with that of DC-T cells, the ratio of negative regulatory cells (Treg) was decreased [(4.3±0.8)% vs (8.3±1.1)%]; the release of IL-2, IFN-γ and IL-12 was increased [(201.2±17.3) ng/L, (163.4±13.1)ng/L, (303.3±22.6)ng/L vs 221.8±17.6)ng/L, (190.4±11.7)ng/L vs (80.3±8.6)ng/L]. All the differences were statistically significant ( P<0.01). 100 ng CD 3/KIF20A loaded T cells were observed under microscope, which obviously targeted KIF20A + pancreatic cancer PANC1 cells and had a strongest killing power. At the killing cells to targeting cells ratio of 20∶1 with 4-hour coculture, the killing rate of CD 3/KIF20A-vcDC-T cells on PANC1 cells was (88.6±2.6)%, which was significantly higher than (68.4±3.4)% and (39.2±2.1)% in the CD3/KIF20A-DC-T group and (39.2±2.1)% in the DC-T group, increasing by 20% and at lease 45%, respectively. Conclusions:DC-T cells loaded with CD 3/KIF20A antibody can significantly increase the killing rate of KIF20A positive pancreatic cancer PANC1 cells, and vitamin C intervention can further enhance the killing ability of antibody loaded T cells.

To construct recombinant eukaryotic expression plasmid vector of human IL-34 gene, and to study the effects of IL-34 expressed by human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on THP-1 cells. Full-length IL-34 encoding sequence was amplified by PCR. And this fragment was cloned into the plasmid pIRES2-EGFP. Western blotting and ELISA were used to analyze the expression of IL-34 in hBM-MSCs. THP-1 cells were cultured with hBM-MSCs medium containing IL-34 protein. Real-time PCR detected the effects of IL-34 on the expression of IL-10 and TNFα in THP-1 cells. Restrictive enzyme analysis and sequencing demonstrated that IL-34 eukaryotic expression vector was successfully constructed. IL-34 protein expressed by hBM-MSCs could promote IL-10 and TNFα expression in THP-1 cells. Those results show that IL-34 expressed by hBM-MSCs has regulating effect on THP-1 cells.

OBJECTIVETo analyze the drug resistance and drug resistance genes of imipenem-resistant Pseudomonas aeruginosa (IRPA) strains isolated from burn wards.

METHODSFrom June 2011 to June 2012, 30 strains of IRPA were isolated from wound excretion, sputum, and venous catheter attachment from burn patients hospitalized in Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine. Drug resistance of the IRPA to 12 antibiotics commonly used in clinic, including ceftazidime, amikacin, ciprofloxacin, etc., was tested with K-B paper agar disk diffusion method. Metallo-β-lactamase (MBL)-producing IRPA was detected by synergism test with imipenem-2-mercaptoethanol. Plasmid of IRPA was extracted, and it was inserted into competent cells, producing transformation strains (TSs). Drug resistance of TSs to imipenem and the MBL-producing TSs were detected. The genes blaIMP, blaVIM, blaOXA-1, blaOXA-2 and blaOXA-10 of IRPA and the TSs were detected by polymerase chain reaction. The drug resistance of IRPA producing MBL or OXA enzyme was summed up.

RESULTSThe sensitive rates of the 30 strains of IRPA to the 12 antibiotics were equal to or above 60.0%. Six strains of MBL-producing IRPA were screened. Twenty-four TSs were resistant to imipenem, and 6 strains among them were MBL-producing positive. Among the 30 strains of IRPA, 6 strains and their corresponding TSs carried blaVIM; 20 strains and their corresponding TSs carried blaOXA-10; no strain was detected to carry blaIMP, blaOXA-1 or blaOXA-2. Two strains and their corresponding TSs were detected carrying both blaVIM and blaOXA-10. No significant difference of drug resistance was observed between strains producing only MBL or OXA enzyme, with the same high resistance to β-lactam antibiotics and some degree of sensitivity to aminoglycoside antibiotics. Strains producing enzymes MBL and OXA were all resistant to the 12 antibiotics.

CONCLUSIONSIRPA strains isolated from burn wards of Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine are multidrug-resistant, and they mainly produce type B and D carbapenemases.

Burns ; microbiology ; Cross Infection ; microbiology ; Drug Resistance, Multiple, Bacterial ; genetics ; Humans ; Imipenem ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; genetics ; isolation & purification

Objective To investigate the function of the left ventricular (LV) myocardial regional contractility in hyperthyroid by measuring the LV rotation and torsion using speckle tracking imaging (STI).Methods 58 patients with hyperthyroidism had accepted 131 I treatment the first time and cured and improved after treatment for 6 months were enrolled.According to the course of disease,they were divided into two groups:Group A,duration less than 6 months,28 cases;Group B,duration more than 6 months,30 cases.30 normal cases age and gender matched were enrolled as control group.LV peak rotation and torsion of endocardium and epicardium at basal and apical of levels were measured using STI in groups A and B before and after treatment,and correlation with cardiac function and structure parameters,heart rate,blood pressure,and the thyroid hormone were analyzed.Results ①Comparing group A and group B before and after treatment with control group,there was no statistically significant in the LV structure and function parameters (LVDd,LVDs,IVSd,PWd,LVEF) (P ＞0.05).②As for LV peak rotation of endocardium and epicardium at apical levels (EN PAR,EP-PAR) before treatment,group A was higher than the control group (P ＜0.05),group B was lower than the control group (P ＜0.01);After treatment,group A has improved (P ＜0.01),group B has improved only in EP-PAR (P ＜0.05),and there was no statistically significant compared with the control group (P ＞0.05).③ LV peak torsion of endocardium and epicardium (EN-Ptor,EP-Ptor) in group A was higher than the control group before treatment (P ＜0.05),group B was lower than the control group (P ＜0.01) ;After treatment,group A has improved (P ＜0.05),group B has only improved in EP-Ptor(P ＜0.05),and comparing with the control group,there was no statistically significant (P ＞0.05).④LV peak apical rotation and LV torsion were positively correlated with systolic blood pressure,heart rate,E-peak,A-peak,LVOT-V in different degree (P ＜0.01 or P ＜0.05),but no correlation with FT3,FT4,TSH (P ＞0.05).Conclusions Myocardial contractile function strengthens in early patients with hyperthyroidism and lessens with the extension of the course.Have not yet appeared heart diseases in patients with hyperthyroidism whose myocardial regional systolic function had changed,short duration can recover after treatment,but the long duration can not restore completely.Change of myocardial motion of patients with hyperthyroidism is associated with blood flow dynamics.

Objective To study the ventricular-arterial coupling in the patients with type 2 diabetes mellitus (DM) by ultrasound.Methods Eighty patients with DM were divided into 2 groups:normal left ventricular ejection fraction (EF) group (DMN,EF≥50 ％,n =40) and abnormal EF group (DMA,EF＜50％,n =40).At the same time,42 healthy volunteers were selected as a control group.The left ventricular (LV) relative wall thickness (RWT),mass index (LVMI),stroke volume (SV),stroke works (SW),ratepressure product (RPP),systemic vascular resistance index (SVRI),LV end-systolic elastance (Ees),arterial elastance index (Ea) and ventricular vascular index (VVI) were measured and calculated.Longitudinal strain (LS) of myocardial segment including base(LSBA),papillary muscle (LSPM) and apex (LSAP) were analyzed by two-dimensional speckle tracking imaging.Results (1) Compared with the control,the RWT and LVMI were all increased (P ＜0.01),but the LSBA,LSPM and LSAP were decreased (P ＜ 0.01) in the DMN and DMA groups (P ＜0.01).In DMA group,the RWT,LSBA,LSPM and LSAP were decreased (P ＜0.01).Compared with the DMN group,the LSBA,LSPM and LSAP were decreased in DMN group (P ＜0.01).(2) Compared with the control,the Ea,VVI,RPP and SVRI were increased,but the Ees was decreased (P ＜0.05)in DMA group (P ＜0.01).In the DMN,RPP was increased compared with the control group (P ＜0.01).Compared with the DMN group,the Ea,VVI,RPP and SVRI were increased,but Ees was decreased in the DMA (P ＜0.05).(3)The LSBA,LSPM and LSAP were all positively correlated with VVI(P ＜0.01).Multiple regression analysis showed that the LSAP,RWT,LVMI and SW were independent predictor of VVI (b' =-0.613,-0.290,0.290 and-0.205,P ＜ 0.05).Conclusions The ventricular-arterial coupling is normal in the DMN group,but is abnormal in DNA group.LSAP is independent predictors for ventricular-arterial coupling.

Objective To evaluate the clinical efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with thermochemotherapy in the treatment of locally advanced pancreatic cancer (LAPC).Methods From June 2008 to June 2011,70 patients with LAPC were divided into radiotherapy group (30 patients) and combination group (40 patients).Radiotherapy used 3D-CRT with a 90％ to 95％ isodose curve,a single dose of 1.8 to 2.OGy,and total radiation dose 50 ～ 70 Gy.The combination group patients received simultaneous thermotherapy at 41.5 ～43.5 ℃ (1 h/fraction,twice a week for 6 times),and hyperthermia given simultaneously injected using arsenic trioxide 20 mg,recombinant mutant human tumor necrosis factor(rmhTNF) intravenous infusion of 10 million U,4 to 6 times,or 3D-CRT at the same time and the treatment given after gemcitabine(0.6 ～ 1.0 g/m2) on Days dl and 8 and cisplatin (DDP) (20 ～ 30 mg/m2) on Days d1-3 intravenous infusion,repeated every 28 days for 3 ～ 6 cycles.Results At 3 months after treatment,the total response (complete remission and partial remission) rate was 70.0％ (49/70),the efficiency of radiotherapy combined with chemotherapy,and radiotherapy combined with thermo-chemotherapy were 56.5％ and 88.2％,and the radiotherapy alone group was 56.7％.There were significant difference in efficiency between radiotherapy combined with thermo-chemotherapy group compared to radiotherapy-chemotherapy group and radiotherapy group (x2 =4.68,4.98,P ＜ 0.05),the last two groups showed no significant difference (P ＞ 0.05).The 1-year and 2-year survival rate was 46.8％ and 20.3％,respectively.The 1-year and 2-year survival rates were 52.4％ and 26.7％ in combination group,and 42.5％ and 16.2％ in radiotherapy group (x2 =14.17,P ＜ 0.05 ; x2 =9.74,P ＜ 0.05).No serious complications such as perforation,bleeding,and high fever were seen during treatment and follow-up.Conclusions 3D-CRT combined with thermochemotherapy is well tolerated and is relatively effective for the LAPC patients.