Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

Objective:To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer (NSCLC) in a real-world study.Methods:Data of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022 (retrospective cohort) and from January 2023 to December 2023 (prospective cohort) were collected. The patients were divided into the combination group ( n=40) and radiotherapy group ( n=44) based on whether they received sequential immunotherapy or not. The progression-free survival (PFS) and overall survival (OS) between two groups were compared using standardized mortality ratio weighting (SMRW). Univariate Cox proportional hazards model, multivariate regression analysis, multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups. E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies. Additionally, the percentage of CD4 +T cells, CD8 +T cells and natural killer (NK) cells, and CD4 +/CD8 + T cell ratio before and after treatment between two groups were compared using analysis of covariance. Results:Among 84 patients, 77 (92%) cases were male and 7 (8%) were female. Among them, 42 (50%) were aged 65 years or older. The variables showed high homogeneity after SMRW, with a standardized mean difference of less than 0.1. In the combination group, the median PFS [17.0 months vs. 7.0 months, HR=0.260, 95% CI: 0.130-0.490, P<0.001] and OS [not reached vs. 24.0 months, HR=0.210, 95% CI: 0.070-0.590, P=0.002] were significantly longer compared to that in the radiotherapy group, with statistically significant differences. The study results were confirmed by robustness and sensitivity analyses. After treatment, patients in the combination group showed a statistically significant increase in the percentage of CD4 + T cells and NK cells, and CD4 +/CD8 + T cell ratio, as well as a decrease in the percentage of CD8 + T cells compared to those in the radiotherapy group (all P<0.05). Conclusions:Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage III NSCLC patients. The survival benefit is even greater when combined with chemotherapy. The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

Objective:To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer (NSCLC) in a real-world study.Methods:Data of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022 (retrospective cohort) and from January 2023 to December 2023 (prospective cohort) were collected. The patients were divided into the combination group ( n=40) and radiotherapy group ( n=44) based on whether they received sequential immunotherapy or not. The progression-free survival (PFS) and overall survival (OS) between two groups were compared using standardized mortality ratio weighting (SMRW). Univariate Cox proportional hazards model, multivariate regression analysis, multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups. E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies. Additionally, the percentage of CD4 +T cells, CD8 +T cells and natural killer (NK) cells, and CD4 +/CD8 + T cell ratio before and after treatment between two groups were compared using analysis of covariance. Results:Among 84 patients, 77 (92%) cases were male and 7 (8%) were female. Among them, 42 (50%) were aged 65 years or older. The variables showed high homogeneity after SMRW, with a standardized mean difference of less than 0.1. In the combination group, the median PFS [17.0 months vs. 7.0 months, HR=0.260, 95% CI: 0.130-0.490, P<0.001] and OS [not reached vs. 24.0 months, HR=0.210, 95% CI: 0.070-0.590, P=0.002] were significantly longer compared to that in the radiotherapy group, with statistically significant differences. The study results were confirmed by robustness and sensitivity analyses. After treatment, patients in the combination group showed a statistically significant increase in the percentage of CD4 + T cells and NK cells, and CD4 +/CD8 + T cell ratio, as well as a decrease in the percentage of CD8 + T cells compared to those in the radiotherapy group (all P<0.05). Conclusions:Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage III NSCLC patients. The survival benefit is even greater when combined with chemotherapy. The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the effect of different reconstruction points of intrauterine applicator on the source dwell positions and plan dosimetry in intracavitary brachytherapy for cervical cancer.Methods:Clinical data of 43 patients with cervical cancer who had completed radical radiotherapy in Liuzhou Workers' Hospital from May 2020 to October 2022 were retrospectively analyzed. Among 43 patients, aged 32-79 years, 40 cases were diagnosed with squamous carcinoma and 3 cases of adenocarcinoma. All patients received external irradiation for 50.4 Gy / 28 fractions and CT-guided intracavitary brachytherapy (45° intrauterine applicator) was 36 Gy / 6 fractions. Brachytherapy was performed by using Fletcher applicator, the curvature of intrauterine applicator were 15°, 30°and45°. Two sets of brachytherapy plans were simulated for each patient. One set of plans extracted the simulated CT positioning images and the original plan of the patient's brachytherapy. The reconstruction point of the curved part of the 45° intrauterine applicator was adjusted to slice-by-slice reconstruction. The plan was optimized to meet clinical requirements according to the prescription, which was called the slice-by-slice group. In the other set of plans, slice-by-slice group was used as a template. The reconstruction points of the curved section of the 45° intrauterine applicator were adjusted to 1, 3, 5, and 7, without modifying the applicator weights and other parameters, which was called the average group 1, 3, 5 and 7. The deviation analysis of 15°, 30° and 45° intrauterine applicator with different number of reconstruction points was carried out, the reconstruction deviation of 45°, 30° and 15° intrauterine applicator at different reconstruction points was compared. Paired-sample t-test or Wilcoxon signed rank test were used to compare the differences in high-risk clinical target volume (HR-CTV) D 50%, D 90%, D 100%, V 100%, V 150%, V 200% and conformity index (CI) as well as D 2 cm3, D 1 cm3 and D 0.1 cm3 in bladder, rectum, and small intestine between two groups of 45° intrauterine applicator. Results:The reconstruction deviation in the average group was mainly from the vertical direction of the 45° intrauterine applicator. The mean reconstruction deviations of 45° (1, 3, 5, 7 reconstruction points), 30° (1, 3, 5 reconstruction points) and 15° (1, 2 reconstruction points) were 1.30 mm, 0.32 mm, 0.14 mm and 0.08 mm; 0.57 mm, 0.14 mm and 0.06 mm; 0.14 mm and 0.06 mm, respectively. There was no significant difference in the parameters of high-risk clinical target volume (HR-CTV) in the slice-by-slice group compared with the average group 5 and 7 (all P>0.005), and no significant difference was found between the average group 5 and 7 (all P>0.005). There were no statistically significant differences in bladder and rectum doses between the slice-by-slice group and the average groups or within the average groups (all P>0.005). The parameters of small intestine in the slice-by-slice group were higher than those of the average group 1, the difference was statistically significant ( P=0.002,<0.001,<0.001). The dose of small intestine in the slice-by-slice group was not statistically significant compared with those in the average group 5 and 7 (both P>0.005). The dose of small intestine in the average group 5 was not statistically significant compared with that in the average group 7 ( P>0.005). The small intestine dose deviations of D 0.1 cm3, D 1 cm3 and D 2 cm3 in the average groups at 1 reconstruction point were 2.41%±1.70%, 1.95%±1.27% and 1.71%±1.10%, respectively. Conclusion:The number of reconstruction points is recommended to be no less than 1, 3 and 5 of the curved part of the 15°, 30°and 45° Fletcher intrauterine applicator, respectively, during intracavitary brachytherapy for cervical cancer.

Objective:To investigate the improvement of radiation-induced cognitive dysfunction and its preliminary mechanism by Ilex pubescens var.kwangsiensis.Methods:SPF grade male Kunming mice were randomly divided into control group(Control),Ilex pubescens var.kwangsiensis(IP),radiation group(Rad)and radiation+Ilex pubescens var.kwangsiensiss group(Rad+IP),with 10 mice in each group.Morris water maze test and dark avoidance test were used to detect the changes in cognitive function of mice before and after drug intervention.Hematoxylin-eosin(HE)staining and electron microscopy were used to observe the changes of brain histopathology and ultrastructure in the hip-pocampus of mice.The expressions of nuclear factor E2-associated factor 2(Nrf2),heme oxygenase 1(HO-1),man-ganese superoxide dismutase(MnSOD),B-cell lymphoma/leukemia-2(Bcl-2)and Bcl-2 associated X protein(Bax)were detected by immunohistochemical assay.Results:The expressions of MnSOD and Bcl-2 in hippocampal tissue of mice in Rad group were significantly decreased,the expressions of Nrf2,Bax and HO-1 were significantly increased,and the nuclear translocation of Nrf2 was also significantly increased.After intervention,he expressions of MnSOD,Nrf2 and HO-1 were significantly increased,and the apoptosis rate was significantly decreased.Conclusion:Ilex pu-bescens var.kwangsiensis improved cognitive dysfunction in mice after radiation,and the mechanism may be related to Nrf2 activation and regulation of HO-1 transcription and expression,reducing oxidative stress damage.

Objective To investigate the feasibility and effect of simple support bracket combined with one stitch suture in terminal ileostomy of two stomas during anus-preserving radical resection in low rectal cancer patients. Methods Retrospectively analysis was performed for rectal cancer patients with high risk factors for postoperative anastomotic leakage, who admitted to the Department of General Surgery our hospital from December 2019 to May 2021. The patients underwent laparoscopic-assisted low rectal cancer radical resection and terminal ileostomy. There were two groups including 35 patients in the group of simple bracket combined with one stitch suture, and 35 patients in the group of conventional suture. Preoperative and postoperative clinical data were analyzed. Results General data of two groups were similar. No difference statistical significantly in the rate of postoperative stoma‐related complications between the two groups ((P>0.05). All patients were without any severe complications. All stomas were successfully closed. The time of first-stage ileostomy (13.77±2.02) min vs. (22.66±3.64) min (P<0.001), second-stage stoma closure time (88.14±28.03) min vs. (103.29±30.96) min (P=0.04), and postoperative total time in hospital (14.54±2.32) d vs. (17.34±4.57) d (P=0.002) were shorter in simple bracket combined with one stitch suture group; both total cost in the hospital of first-stage operation (42 057.98±4 938.69) yuan vs. (44 728.46±5 223.62) yuan (P=0.03), and second-stage stoma closure blood loss (17.94±9.83) mL vs. (25.86±8.24) mL (P=0.001) lower compared with that in conventional suture group. Conclusions Simple support bracket combined with one stitch suture ileostomy did not increase postoperative stoma-related complications compared with conventional suture. However, it decreased the time for both first-stage ileostomy and second-stage stoma closure, and total cost in hospital. Therefore, it could be used for prophylactic ileostomy in low rectal cancer.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.