Objective:To investigate the value of CT radiomic model based on analysis of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer in differentiating stage T1-2 from stage T3-4 gastric cancer.Methods:This study was a case-control study. Totally 465 patients with gastric cancer treated in Affiliated People′s Hospital of Jiangsu University from December 2011 to December 2019 were retrospectively collected. According to postoperative pathology, they were divided into 2 groups, one with 150 cases of T1-2 tumors and another with 315 cases of T3-4 tumors. The cases were divided into a training set (326 cases) and a test set (139 cases) by stratified sampling method at 7∶3. There were 104 cases of T1-2 stage and 222 cases of T3-4 stage in the training set, 46 cases of T1-2 stage and 93 cases of T3-4 stage in the test set. The axial CT images in the venous phase during one week before surgery were selected to delineate the region of interest (ROI) at the primary lesion and the extramural gastric adipose tissue adjacent to the cancer areas. The radiomic features of the ROIs were extracted by Pyradiomics software. The least absolute shrinkage and selection operator was used to screen features related to T stage to establish the radiomic models of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer. Independent sample t test or χ2 test were used to compare the differences in clinical features between T1-2 and T3-4 patients in the training set, and the features with statistical significance were combined to establish a clinical model. Two radiomic signatures and clinical features were combined to construct a clinical-radiomics model and generate a nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of each model in differentiating stage T1-2 from stage T3-4 gastric cancer. The calibration curve was used to evaluate the consistency between the T stage predicted by the nomogram and the actual T stage of gastric cancer. And the decision curve analysis was used to evaluate the clinical net benefit of treatment guided by the nomogram and by the clinical model. Results:There were significant differences in CT-T stage and CT-N stage between T1-2 and T3-4 patients in the training set ( χ2=10.59, 15.92, P=0.014, 0.001) and the clinical model was established. After screening and dimensionality reduction, the 5 features from primary gastric cancer and the 6 features from the adipose tissue outside the gastric wall beside cancer established the radiomic models respectively. In the training set and the test set, the AUC values of the primary gastric cancer radiomic model were 0.864 (95% CI 0.820-0.908) and 0.836 (95% CI 0.762-0.910), and the adipose tissue outside the gastric wall beside cancer radiomic model were 0.782 (95% CI 0.731-0.833) and 0.784 (95% CI 0.702-0.866). The AUC values of the clinical model were 0.761 (95% CI 0.705-0.817) and 0.758 (95% CI 0.671-0.845), and the nomogram were 0.876 (95% CI 0.835-0.917) and 0.851 (95% CI 0.781-0.921). The calibration curve reflected that there was a high consistency between the T stage predicted by the nomogram and the actual T stage in the training set ( χ2=1.70, P=0.989). And the decision curve showed that at the risk threshold 0.01-0.74, a higher clinical net benefit could be obtained by using a nomogram to guide treatment. Conclusions:The CT radiomics features of primary gastric cancer lesions and the adipose tissue outside the gastric wall beside cancer can effectively distinguish T1-2 from T3-4 gastric cancer, and the combination of CT radiomic features and clinical features can further improve the prediction accuracy.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective To explore the functional changes of the glial lymphatic system in patients with spontaneous intracerebral hemorrhage(sICH)by MR diffusion tensor imaging(DTI).Methods The clinical and imaging data of 32 sICH patients(sICH group)and 31 healthy volunteers(control group)were retrospectively collected,and the diffusivity values of DTI in different direc-tions were collected from all the subjects,the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index was calculated,the difference of DTI-ALPS index values between the sICH group and the control group was compared,the changes in the function of the glial lymphatic system in sICH patients were evaluated,and the correlation between DTI-ALPS index and clinical indi-cators in sICH patients was further analyzed.Results The DTI-ALPS index of cerebral hemispheres on the lesions side of sICH group was significantly lower than that on the unaffected side(P＜0.01,t=-5.03),and lower than that on the left side of control group(P＜0.01,t=-9.85)and the right side(P＜0.01,t=-8.80).In addition,vascular endothelial growth factor(VEGF)tes-ting was performed in 8 of the 32 patients,and the levels[(187.40±19.11)pg/mL]were significantly higher than the normal range(0-142.20 pg/mL).Conclusion Through the quantitative analysis of the DTI-ALPS index,the damage to the function of the glial lymphatic system of sICH can be reflected,and perhaps the mechanism of pathophysiological changes in the brain after sICH can be reflected from a new perspective by using MR DTI technology.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Objective:To provide strategical reference for large-scale colorectal cancer screening with full regional coverage by analyzing the results of the first colorectal cancer screening in the target population in Linhai city,Zhejiang Province. Methods:The target population of 50-74 years old in Linhai were invited to take part in the colorectal cancer screening program from 2020 to 2021.The risk of colorectal cancer of the participants were preliminarily evaluated by questionnaire and qualitative fecal occult blood test(FOBT),and participants with positive screening results were suggested to take colonoscopy test for further evaluation.The screening results were collected and analyzed. Results:A total of 71 942 people were screened from 2020 to 2021,and 15 1 70 of them were found positive in preliminary screening.The positive rate in males was significantly higher than that in females(x 2=724.005,P＜0.001),and the positive rate was highest in the population of 60-69 years old during preliminary screening.The compliance rate of colonoscopy was 24.1 9％with no significant difference between males and females(x 2=0.256,P=0.61 3),showing a decreasing trend as the age increases.From 2020 to 2021,the detection rate of lesions by colonoscopy was 52.92％,with 47 case of colorectal cancer(CRC),333 case of advanced colorectal adenoma,561 case of non-advanced colorectal adenoma and 1 001 case of benign lesions.The detection rate of lesions in males was much higher than that in females(x 2=82.451,P＜0.001).The detection rates of lesions,advanced colorectal adenoma,and non-advanced adenoma showed increasing trends with the age.The compliance rate of colonoscopy,the detection rate of lesions,and the detection rate of CRC,advanced colorectal adenoma,and non-advanced adenoma were 32.94％,69.53％,2.87％,1 6.85％and 1 9.71％,respectively,in participants who were both assessed as high-risk according to questionnaire evaluation and FOBT positive,the highest among all participants.The compliance rate of colonoscopy in 2021 was obviously higher than that in 2020(32.11％vs 1 9.09％,P＜0.001),but no significant difference was found in the detection rate of lesions between 2021 and 2020(P＞0.05). Conclusion:From 2020 to 2021,the compliance rate of colonoscopy was low and the detection rate of colorectal lesions was high during the screening of colorectal cancer in the target population in Linhai,Zhejiang Province.It is necessary to enhance the public awareness of the importance of colorectal cancer screening,standardize the enrollment criteria,and improve the compliance of colonoscopy,in orderto give full play to primary screening in the general public.

Objective:To evaluate a wound diagnosis and treatment mode with integrated medical care in the repair of chronic infectious wounds plus bone exposure at lower extremities.Methods:A retrospective analysis was conducted of the 64 patients with chronic infectious wound plus bone exposure at the lower 1/3 of the leg who had been admitted to Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University from January 2019 to December 2021. The patients were divided into 2 groups according to the wound diagnosis and treatment mode. In the observation group of 31 patients subjected to the wound diagnosis and treatment mode with integrated medical care led by specialist nurses, there were 24 males and 7 females with an age of (53.6±12.4) years, the wound was located at the tibial side in 15 cases and at the fibular side in 16 cases, the wound areas averaged [28.27 (23.56, 37.70) cm 2], and the time from injury to treatment was (27.3±4.1) d. Evaluation of the patient's condition, wound diagnosis and formulation of treatment protocols were performed jointly by a doctor-nurse team after the patients were admitted, and continuous diagnosis and treatment of the wounds were carried out mainly by specialist nurses during the doctors' follow-up. In the control group of 33 patients subjected to the conventional wound diagnosis and treatment mode led by doctors, there were 25 males and 8 females with an age of (51.3±14.3) years, the wound was located at the tibial side in 17 cases and at the fibular side in 16 cases, the wound areas averaged [27.49 (17.84, 40.45) cm 2], and the time from injury to treatment was (27.6±4.0) d. The 2 groups were compared in the wound healing rate, wound recurrence rate, hospitalization time and patients' satisfaction. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The observation group achieved a significantly higher wound healing rate within 1 month after treatment [83.87% (26/31)] than the control group [60.61% (20/33)], a significantly lower wound recurrence rate within 6 months after treatment [0% (0/31)] than the control group [18.18% (6/33)], significantly shorter hospitalization time [18.0 (15.1, 20.9) d] than the control group [26.8 (18.4, 40.1) d], and significantly higher patients' satisfaction [50 (50, 50) points] than the control group [50 (42, 50) points] (all P<0.05). Conclusion:In the repair of chronic infectious wounds plus bone exposure at lower extremities, the wound diagnosis and treatment mode with integrated medical care led by specialist nurses may result in a higher wound healing rate, a lower wound recurrence rate, a shorter hospital stay and higher patients' satisfaction than the conventional wound diagnosis and treatment mode led by doctors.

Objective:To evaluate the outcome of the patients receiving dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) delivered by first-responders who witnessed the out-of-hospital cardiac arrest (OHCA) before the Emergency Medical Service (EMS) arrived.Methods:We performed a search of the relevant literature exploring major scientific databases. We assessed the quality of the included cohort study according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. Meta-analysis was performed on three outcome indicators (recovery of spontaneous circulation survival to hospital discharge and survival with favourable neurologic outcome) using the Revman5.3 software.Results:A total of 21 studies with 349 822 patients were selected for the meta-analysis, including 182 125 patients in the DA-CPR group and 167 697 in the CPR-only group. The meta-analysis showed no significant difference between the DA-CPR and CPR-only groups in ROSC [ RR=1.10, 95% confidence interval ( CI): 0.94-1.29, P=0.24], survival to hospital discharge ( RR=1.10, 95% CI: 0.90-1.34, P=0.34) and survival with favourable neurologic outcome ( RR=1.01, 95% CI: 0.79-1.28, P=0.97) of the patients in America, Japan and Korea. However, there was a significant difference between the DA-CPR and the CPR-only groups in ROSC ( RR=2.61, 95% CI:1.53-4.46, P=0.0005), survival to hospital discharge( RR=6.08, 95% CI: 1.84-20.04, P=0.003), and survival with favourable neurologic outcome( RR=9.76, 95% CI: 1.87-51.02, P=0.007) of the patients in China. Conclusions:The overall effect of DA-CPR is significantly different for each country. In detail, DA-CPR offers a survival advantage (Return of spontaneous circulation, survival to hospital discharge and survival with favourable neurologic outcome) over CPR alone in China but no advantage in developed countries.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective To evaluate the changes in the expression of hippocampal α7 nicotinic ace-tylcholine receptor (α7nAChR) , acetylcholinesterase ( AChE) and choline acetyltransferase ( ChAT) after sevoflurane anesthesia in neonatal rats. Methods Seventy-two healthy Sprague-Dawley rats of both sexes, aged 7 days, weighing 25-40 g, were divided into 3 groups ( n=24 each) using a random number table method: control group ( group C) , air and oxygen group ( group A∕O) and sevoflurane group ( group S) . Rats were exposed to carrier gas ( air 1 L∕min plus oxygen 1 L∕min) for 2 h in group A∕O. Rats were ex-posed to 3. 4％ sevoflurane in carrier gas for 2 h in group S. Eight rats in each group were selected at 2 h, 1 week and 4 weeks after the end of inhalation, and sacrificed, brains were removed and hippocampal tis-sues were obtained for determination of α7nAChR, AChE and ChAT protein and mRNA by Western blot and real-time polymerase chain reaction, respectively. Results Compared with group A∕O, the expression of α7nAChR mRNA was significantly down-regulated at each time point after the end of inhalation, and the expression of TnAChR was down-regulated at 2 h after the end of inhalation and up-regulated at 1 week after the end of inhalation, the expression of AChE mRNA was up-regulated at 2 h after the end of inhalation and down-regulated at 4 weeks after the end of inhalation, the expression of AChE was down-regulated at 4 weeks after the end of inhalation, the expression of ChAT mRNA was up-regulated at 2 h after the end of in-halation, and the expression of ChAT was down-regulated at each time point after the end of inhalation in group S ( P<0. 05) . Conclusion The expression of hippocampal α7nAChR is down-regulated at first and then up-regulated after sevoflurane anesthesia, the expression of ChAT and AchE in the later period is down-regulated, the tendency of protein expression mentioned above is different from that of its mRNA ex-pression, suggesting that sevoflurane may affect the protein expression through other pathways.

OBJECTIVE： To establish HPLC fingerprint of Mongolian medicine Ramulus Tamarix， and to conduct similarity evaluation and cluster analysis. METHODS： HPLC method was adopted. The determination was performed on Agilent ODS C18 column with mobile phase consisted of methanol-water （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 335 nm， and column temperature was 30 ℃. The sample size was 10 μL. Using quercetin peak as reference， HPLC fingerprint of 10 batches of medicinal sample were drawn. Similarity evaluation was conducted by using Similarity Evaluation System for Chromatographic Fingerprint of TCM （2004 A） so as to confirm common peak. SPSS 17.0 software was used for cluster analysis of those samples. RESULTS： There were 13 common peaks in HPLC fingerprint of 10 batches of samples， and the similarities of them were all greater than 0.95； 2 common chromatographic peaks of quercetin and kaempferol were identified. Results of cluster analysis showed that 10 batches of samples were classified into 2 classes. S8 was clustered into one class； other were clustered into another class. CONCLUSIONS： Established HPLC fingerprint and results of similarity evaluation and cluster analysis can provide reference for quality control of R. Tamarix.