Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.

To investigate the effects of postoperative fusion implantation on the mesoscopic biomechanical properties of vertebrae and bone tissue osteogenesis in idiopathic scoliosis, a macroscopic finite element model of the postoperative fusion device was developed, and a mesoscopic model of the bone unit was developed using the Saint Venant sub-model approach. To simulate human physiological conditions, the differences in biomechanical properties between macroscopic cortical bone and mesoscopic bone units under the same boundary conditions were studied, and the effects of fusion implantation on bone tissue growth at the mesoscopic scale were analyzed. The results showed that the stresses in the mesoscopic structure of the lumbar spine increased compared to the macroscopic structure, and the mesoscopic stress in this case is 2.606 to 5.958 times of the macroscopic stress; the stresses in the upper bone unit of the fusion device were greater than those in the lower part; the average stresses in the upper vertebral body end surfaces were ranked in the order of right, left, posterior and anterior; the stresses in the lower vertebral body were ranked in the order of left, posterior, right and anterior; and rotation was the condition with the greatest stress value in the bone unit. It is hypothesized that bone tissue osteogenesis is better on the upper face of the fusion than on the lower face, and that bone tissue growth rate on the upper face is in the order of right, left, posterior, and anterior; while on the lower face, it is in the order of left, posterior, right, and anterior; and that patients' constant rotational movements after surgery is conducive to bone growth. The results of the study may provide a theoretical basis for the design of surgical protocols and optimization of fusion devices for idiopathic scoliosis.
Humans ; Scoliosis/surgery* ; Spinal Fusion/methods* ; Lumbar Vertebrae/surgery* ; Osteogenesis ; Biomechanical Phenomena/physiology* ; Finite Element Analysis

Background: Patients with functional dyspepsia (FD) are accompanied by different degree of psychological stress, and clinicians usually have insufficient quantitative assessment of patients’psychological stress. Aims: To explore the effect of psychological stress assessed by 4-item perceived stress scale (PSS-4) and 10-item perceived stress scale (PSS-10) on dyspepsia symptoms, anxiety, depression, somatization and quality of life in FD patients. Methods: A total of 357 FD patients met Rome IV criteria from March 2021 to March 2022 at Affiliated Hospital of North Sichuan Medical College were recruited. Score of PSS-4, PSS-10, generalized anxiety disorder-7 (GAD-7), patient healthy questionnaire-9 (PHQ-9), adapted patient healthy questionnaire-15 (adapted PHQ-15), dyspepsia symptom severity (DSS), Nepean dyspepsia index-short form (NDI) were performed. Effects of PSS-4, PSS-10 on dyspepsia symptoms, anxiety, depression, somatization and quality of life in FD patients were analyzed. Results: Correlation analysis showed that PSS-4 (r=0.152, P=0.004) and PSS-10 (r=0.194, P=0.000) were correlated with DSS; PSS-4 (r=0.341, P=0.000) and PSS-10 (r=0.389, P=0.000) were correlated with adapted PHQ-15; PSS-4 (r=0.239, P=0.000) and PSS-10 (r=0.327, P=0.000) were correlated with NDI; PSS-4 (r= 0.561, P=0.000) and PSS-10 (r=0.680, P=0.000) were correlated with anxiety; PSS-4 (r=0.449, P=0.000) and PSS-10 (r= 0.524, P=0.000) were correlated with depression. Multiple linear regression analysis showed that psychological stress assessed by PSS-4 (β=0.180, P=0.000), DSS (β=0.390, P=0.000) and FD classification (β=-0.116, P=0.024) were the influencing factors of NDI, and the psychological stress assessed by PSS-10 (β=0.268, P=0.000), DSS (β=0.360, P=0.000) and FD classification (β=-0.116, P=0.021) were the influencing factors of NDI. Conclusions: Psychological stress assessed by PSS-4, PSS-10 have effects on anxiety, depression, somatization, DSS and NDI in FD patients, and PSS-4 is shorter. These results suggest that PSS-4 can be used clinically to assess quickly and initially the impact of psychological stress on FD patients.

Objective:To investigate the characteristics of newly diagnosed patients with chronic obstructive pulmonary disease (COPD) in Shenzhen primary care.Methods:Random sampling was conducted in 10 jurisdictions of Shenzhen, permanent residents who were over 40 years old and lived for more than 6 months were included for lung function test, COPD Population Screener (COPD-PS) questionnaire and information survey, the prevalence of COPD was estimated, and statistical comparison was made between the two groups of subjects with newly diagnosed and previously diagnosed COPD.Results:Among 3 916 subjects, 3 591 had completed the whole screening process. The results showed that 280 COPD patients were diagnosed and the estimated standardized prevalence of COPD was 5.92% (95% CI: 4.05-8.34). Among them, 251 (89.64%) were newly diagnosed COPD patients and 29 (10.36%) were previously diagnosed COPD patients. Compared with previously diagnosed COPD, the proportion of female in the newly diagnosed COPD was higher (50.20% vs 10.34%, P<0.001), educational level in the newly diagnosed COPD was lower (the proportion of primary school and below was higher, 42.23% vs 20.69%, P=0.023), the proportion of those with frequent wheezing symptoms in the newly diagnosed COPD was lower (4.78% vs 51.72%, P<0.001), the proportion of those with mild degree of airway obstruction (GOLD 1) in the newly diagnosed COPD was higher (81.67% vs 20.69%, P<0.001). The detection rates of COPD-PS in newly diagnosed COPD and previously diagnosed COPD were 43.03% and 41.38% respectively. The area under the receiver operating characteristic curve of COPD-PS was 0.705. Conclusion:The phenomenon of insufficient diagnosis of COPD in Shenzhen primary care is common and we should vigorously popularize pulmonary function examination.

Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.
Pharmaceutical Preparations

Objective:To improve accuracy of prediction amount of length of gastric tube placed through nose and reduce occurrence of adverse events thorough clinical observation of measurement of length of nasogastric tube placement in critically ill children.Methods:Using the convenient sampling method, critically ill children who were hospitalized and needed a nasogastric tube in Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital Affiliated to Capital Medical University were selected from April to September 2019. The prediction method of "nos-ear-xiphoid (NEX) increased by 5 cm" (NEX+5 cm) was adopted. The values of placed length in this study were collected and compared with those predicted by traditional measurement method (namely NEX) , improved "nose-ear-mid-umbilicus" (NEMU) and formula method.Results:A total of 52 critically ill children were enrolled in this study. The length of placed nasogastric tube was 31.5 (28.3, 35.8) cm, and 43 cases (82.7%) were determined to be qualified by X-ray. The length of gastric tube required to be placed in children was 27.0 (24.1, 31.0) cm according to the NEX method, and the length of gastric tube required to be placed in children was 26.1 (22.5, 29.0) cm measured by the formula method. Both were shorter than that measured by NEX+5 cm, and the differences were statistically significant ( P<0.01) . The NEMU method measured the length of gastric tube to be inserted into the child to be 31.0 (28.3, 36.0) cm. Compared with the length measured by NEX+5 cm, and the difference was not statistically significant ( P>0.05) . Conclusions:This study uses NEX+5 cm to predict the actual length of the gastric tube inserted through the nose. The accuracy is relatively high and the operation method is simple. It is necessary to consider individual differences in clinical applications, especially the large variability in infants and young children. After catheterization, abdominal ultrasound, X-ray and other auxiliary examination methods should be used to determine the location of catheterization, and individualized catheterization programs should be given to children according to different therapeutic objective.

Objective:To investigate the effect and tolerance of non-invasive ventilation (NIV) with helmet in patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the effect on improving blood gas, alleviating dyspnea and the occurrence of complications.Methods:Patients with AECOPD and respiratory failure admitted to emergency intensive care unit (EICU) and respiratory intensive care unit (RICU) of the First Affiliated Hospital of Zhengzhou University from January 1st, 2018 to May 31st, 2019 were enrolled. After obtaining the informed consent of the patients or their authorized family members, the patients were divided into two groups: the helmet group and the facial mask group by random number table. NIV was carried out by using helmet or facial mask, respectively. During the course of NIV (immediately, 1 hour, 4 hours and at the end of NIV), the tolerance score, blood gas analysis, heart rate (HR), respiratory rate (RR) of patients were monitored, and the incidence of tracheal intubation, in-hospital mortality and complications were observed. Kaplan-Meier survival curve was plotted to analyze the 30-day cumulative survival of the two groups.Results:A total of 82 patients with AECOPD and respiratory failure were included during the study period. After excluding patients with the oxygenation index (PaO 2/FiO 2) > 200 mmHg (1 mmHg = 0.133 kPa), with tracheal intubation or invasive ventilation, suffering from acute myocardial infarction, severe trauma within 2 weeks, excessive secretion, sputum discharge disorder or refusal to participate in the study, 26 patients were finally enrolled in the analysis, randomly assigned to the helmet group and the facial mask group, with 13 patients in each group. The PaO 2/FiO 2 after NIV of patients in both groups was increased significantly as compared with that immediately after NIV, without significant difference between the two groups, but the increase in PaO 2/FiO 2 at the end of NIV compared with immediately after NIV in the helmet group was significantly higher than that in the facial mask group (mmHg: 75.1±73.2 vs. 7.7±86.0, P < 0.05). RR at each time point after NIV in the two groups was lower than that immediately after NIV, especially in the helmet group. There were significant differences between the helmet group and facial mask group at 1 hour, 4 hours, and the end of NIV (times/min: 17.5±4.1 vs. 23.1±6.3 at 1 hour, 16.2±2.5 vs. 20.0±5.5 at 4 hours, 15.5±2.5 vs. 21.2±5.9 at the end of NIV, all P < 0.05). The NIV tolerance score of the helmet group at 4 hours and the end was significantly higher than that of the facial mask group (4 hours: 3.9±0.3 vs. 3.3±0.9, at the end of NIV: 3.8±0.6 vs. 2.9±0.9, both P < 0.05). There was no significant difference in the improvement of pH value, arterial partial pressure of carbon dioxide (PaCO 2), or HR between helmet group and facial mask group. The total number of complications (cases: 3 vs. 8) and the nasal skin lesions (cases: 0 vs. 4) in the helmet group were significantly less than those in the facial mask group (both P < 0.05). Only 2 patients in the helmet group received endotracheal intubation, and 1 of them died; 5 patients in the facial mask group received endotracheal intubation, and 3 of them died; there was no significant difference between the two groups (both P > 0.05). The Kaplan-Meier survival curve analysis showed that the cumulative survival rate of 30 days in the helmet group was lower than that in the facial mask group, but the difference was not statistically significant (Log-Rank test: χ 2 = 1.278, P = 0.258). Conclusion:NIV with helmet has better comfort for patients with AECOPD combined with respiratory failure, and better effect on improving oxygenation and relieving dyspnea, and its effect on carbon dioxide emissions is not inferior to that of traditional mask NIV.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

BACKGROUND: In our previous studies, zinc-calcium-phosphate (Zn-Ca-P) coating has been successful y prepared on the surface of AZ31 magnesium al oy, which improves the corrosion resistance of the al oy. OBJECTIVE: To analyze the hemocompatibility of Zn-Ca-P coated AZ31 magnesium al oy in vitro. METHODS: Zn-Ca-P coating was prepared on the surface of AZ31 magnesium al oy using chemical transformation. Afterwards, the characteristics of the Zn-Ca-P coating were investigated using scanning electron microscope, and X-ray diffraction analyzed its components. Besides, hemocompatibility in vitro was evaluated by platelet adhesion assay, dynamic clotting time test and hemolysis test. RESULTS AND CONCLUSION: Under scanning electron microscope, a flower-like coating was formed ont surface of the AZ31 magnesium al oy, with the main chemical component of insoluble phosphates Zn3(PO4)2?4H2O. And some round distortionless blood platelets adhered to the surface of AZ31 magnesium al oy, with no pseudopodia. In dynamic clotting time test, the long curve of Zn-Ca-P coating tended to descend indicating better anticoagulant activity. And the hemolysis rate was below 5%. In conclusion, Zn-Ca-P coating has good hemocompatibility in vitro.