Objective To investigate the effect of different doses of statins on the clinical efficacy and safety outcome of intravenous thrombolytic therapy of urokinase in patients with acute ischemic stroke (AIS). Methods Based on a large prospective, multicenter study, the Chinese Intravenous Thrombolysis Registry for AIS within 4.5 h of onset (INTRECIS) database, clinical data of 898 patients with urokinase intravenous thrombolysis for AIS were retrospectively analyzed. According to the amount of statin used during hospitalization, the patients were divided into 132 patients in no-statin group, 591 patients in conventional statin group and 175 patients in intensive statin group. Clinical outcome measures included 14-day improvement in the National Institutes of Health Stroke Scale (NIHSS) and 90-day excellent prognosis (improved Rankin score ≤1 point). Safety measures included recurrent stroke, bleeding events, and 90-day all-cause mortality. Results After adjusting for differences in baseline characteristics (age, coronary heart disease, diabetes, atrial fibrillation, systolic blood pressure, OTT, DNT, previous anti-plate use, blood glucose, and treatment in Class A hospitals), NIHSS scores improved at 14 days after admission and excellent prognosis at 90 days after admission in convention-dose and intensive statin groups were superior to those in no-statin group (P<0.05); Univariate and multivariate analysis of safety outcome indicators showed no statistically significant differences in stroke recurrence and bleeding events among the three groups (P>0.05); The 90-day all-cause mortality was significantly higher in no-statin group (10.6%) than in convention-dose statin group (2.0%) and intensive dose statin group (2.9%) (P<0.01). Conclusions In patients with AIS who were treated with intravenous urokinase thrombolytic therapy, intensive statin use was associated with improved 14-day NIHSS score and near-term prognosis without increasing the risk of stroke recurrence and bleeding events. Statin use is beneficial to reduce mortality.

Neoantigen pulsed dendritic cell vaccine (Neo-DCVac) is a new type of tumor immunotherapy. Neoantigen is strong immunologic and tumor-specific mutated peptides expressed in a tumor. Neo-DCVac is a therapeutic modality based on the uptake and processing of neoantigens by dendritic cells and their delivery and activation of T cells to trigger the body's immune response for anti-tumor effects. The development of individualized Neo-DCVac based on high-throughput sequencing is expected to be a new direction for precision immunotherapy of tumors. In this review, we discuss construction of individualized Neo-DCVac, clinical application of combination therapy in solid tumors, suitable population for vaccination and the current limitations of Neo-DCVac, aiming to provide a theoretical reference for research on tumor immunotherapy.

Objective To investigate the effect and mechanism of transplantation of neuregulin1 (NRG1) gene-modified bone marrow mesenchymal stem cells (BMSCs) on the repair of hemi-transected spinal cord injury (SCI) in rats. Methods Isolated and cultured rat BMSCs, followed by transfection with the NRG1 gene. The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method, and the proliferation activity of the BMSCs was detected by cell counting method. Forty-three healthy 8-week-old SD rats were randomly divided into control group (n=10), SCI model group (n=10), BMSCs group (n=10), and NRG1-BMSCs group (n=13). After establishing the spinal cord hemisection model, animals received in-situ transplantation of BMSCs or NRG1-BMSCs. On the 1, 7, 14, 21, and 28 days after transplantation, the hind limb motor function was evaluated using BBB score and inclined plate test; on the 7th day after transplantation, the migration and distribution of transplanted cells was monitored using a fluorescence microscope; on the 28th day after transplantation, the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining; cell apoptosis using TUNEL staining, and levels of endoplasmic reticulum stress-related proteins X-box binding protein 1 (XBP1), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), ATF6, glucose-regulated protein 78 (GRP78)] and apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated protein X (Bax)] in rat spinal cord tissues using Western blotting. Results BMSCs were successfully isolated, cultured, and transfected with the NRG1 gene. ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner (P<0.05). The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs (P<0.05). On the 21 and 28 days after transplantation, the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group (P<0.05). However, it did not reverse to the level in control group (P<0.05). On the 28th day after transplantation, compared with the SCI model group and BMSCs group, neuronal pyknosis reduced, the Nissl body density increased, the expression levels of XBP1, CHOP, ATF4, ATF6, GRP78, and Bax, and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group (P<0.05), and the expression level of Bcl-2 significantly increased (P<0.05). Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats. The mechanism may be related to promoting the proliferation activity of BMSCs, inhibiting cell apoptosis, and mitigating endoplasmic reticulum stress.

Objective To investigate the predictive value of new simplified insulin resistance (IR) assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus (T2DM). Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction (LVEF≥50%) who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed. All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain (GLS). According to GLS value, the subjects were divided into the normal group (GLS≥18% group, n=80) and the impaired group (GLS<18% group, n=70). Some new simplified IR assessment indicators were calculated and compared between the two groups, including body mass index (BMI), TG/HDL‑C ratio, triglyceride-glucose (TyG) index, TyG‑BMI index, TyG‑WHR and metabolic score for IR (METS‑IR). Correlation between the GLS and the new simplified IR assessment indexes was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes, with the area under the curve (AUC) calculated. Furthermore, according to whether the subjects were complicated with hypertension, binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS <18%. Results Total 150 were included with aged (54.5±13.7) years with 96 (64.0%) men and 54 (36.0%) women. Compared with the GLS≥18% group, the TG/HDL‑C ratio, TyG index, TyG‑BMI, and METS‑IR of subjects in the GLS<18% group were significantly increased (P<0.05). Pearson correlation analysis showed that TG/HDL‑C ratio, TyG index, TyG‑BMI, TyG‑WHR, and METS‑IR were negatively correlated with GLS (P<0.05). ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18% (AUC=0.678, 95%CI 0.591-0.765, P<0.001). Stratification based on hypertension and further adjusting for confounding factors, TyG index remains significantly associated with GLS<18% (OR=3.249, 95%CI 1.045-10.103, P=0.042). Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction. TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1) gene in proliferation and migration of intrahepatic cholangiocarcinoma (iCCA) cell HuCCT1. Methods HuCCT1 cells with IDH1 gene knockout (HuCCT1^IDH1-/-) were constructed by CRISPR/Cas9 gene editing technology. To investigate the capacities of proliferation, migration and invasion of HuCCT1^WT (HuCCT1 cells with wild-type IDH1 gene) and HuCCT1^IDH1-/- cells, assays of CCK-8, clone formation, scratch and transwell were performed. Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT) associated proteins E-cadherin, N-cadherin, Vimentin, MMP-9, Wnt3a and β-catenin in two groups of cells. The transcriptome sequencing data of HuCCT1^WT and HuCCT1^IDH1-/-cells were analyzed by bioinformatics methods, Western blotting was used to verify the expression of signaling pathway-related proteins. Results Compared with HuCCT1^WT cells, HuCCT1^IDH1-/- cells showed the number of proliferation and clone formation significantly reduced (P<0.05), the proportion of cells blocked in G₂/M phase was significantly increased (P<0.01), the rate of scratch healing was significantly decreased (P<0.01), and the number of migrated cells (P<0.001) and invaded cells (P<0.05) was significantly reduced. qRT- PCR assay showed that the expression levels of IDH1, Vimentin, MMP-9 and genes related to the regulation of G₂/M cycle proliferation, Cyclin A2, Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1^IDH1-/- cells (P<0.05), and the expression of CDH1 mRNA encoding E-cadherin was up-regulated (P<0.01); Western blotting assay showed that the expression level of E-cadherin in HuCCT1^IDH1-/- cells was significantly increased (P<0.05), and the expression level of N-cadherin, Vimentin and MMP-9 protein was significantly decreased (P<0.05) than that in HuCCT1^WT cells. Data of transcriptome sequencing revealed 1476 differentially expressed genes (DEGs) between two groups of HuCCT1 cells. Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response, cell signaling and cell metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK, Rap1, Hippo and TNF, which are closely related to the regulation of proliferation and invasion of tumor cells. Western blotting verification results showed that compared with HuCCT1^WT cells, the relative expression of Wnt3a and β‑catenin proteins of HuCCT1^IDH1-/- cells was significantly decreased (P<0.05). Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells, including cell proliferation, migration, invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

At the beginning of this century, breakthroughs and innovations in disruptive technologies represented by artificial intelligence have profoundly affected the development of human society and have become a central component in leading the new global military transformation. Saving the lives of the wounded and technological innovation are the driving force behind the development of military medicine. How to fight a battle and how to save people is the question that military medicine must answer. Joint all-area combat is a new military concept, representing the development direction of the future combat style, it has a strong strategic guiding significance for the future war and also puts forward higher requirements for the treatment of war injuries. "Platinum ten minutes, gold one hour" is the fundamental law of the battlefield first-line time-saving treatment, the war injury treatment must serve in the joint all-area combat demand and service requirements. This paper discusses the issue of demand or war injury treatment capacity building under the joint all-area combat pasture for criticism and correction.

Based on the background of a multidisciplinary treatment team and the increasing high-quality life aspirations of patients, the preservation of anal function for patients with low rectal cancer has undergone changes in recent years. With the optimization of neoadjuvant therapy, refinement of surgical techniques, and the deepening of the concept of anal preservation after surgery, the concept of anal preservation for low rectal cancer has gradually shifted from traditional simple surgery to comprehensive treatment, and anal preservation surgery tends to be more accurate preservation. The goal of comprehensive treatment is to preserve good anal function and reduce surgical damage. However, comprehensive treatment for anal preservation in low rectal cancer is still in its infancy, and there is no consensus on the strategy planning for anal preservation. Therefore, summarizing various preoperative, intraoperative, and postoperative treatment strategies for low rectal cancer is of great significance for the selection of anal preservation schemes for patients with low rectal cancer. This article focus on exploring the optimization of neoadjuvant therapy models, "watch and wait" plans, the development of anal preservation techniques, and postoperative and preservation strategies, aiming to review the current status of anal preservation strategy planning for low rectal cancer.

Epilepsy is a common neurological disease, has the characteristics of recurrent attacks and long-term treatment, thus bringing great pressure to patients and their families. Therefore, it is particularly important to do a good job of disability assessment. In recent years, with the development of the discipline, academic organizations such as the International League Against Epilepsy (ILAE) and China Association Against Epilepsy (CAAE) have successively updated the definition and diagnostic criteria of epilepsy and seizures. However, some items of epilepsy in the current Criteria for Disability Rating of Military Personnel (Trial) issued by People's Liberation Army (PLA) in 2011 can no longer meet the latest guidelines at home and abroad. Therefore, we suggest that the items related to epilepsy in the Criteria for Disability Rating of Military Personnel (Trial) should be revised to ensure that the disability evaluation being completed fairly and successfully.

Diagnosis and treatment of locally advanced rectal cancer (LARC) must be completed by a collaborative model of a multi-disciplinary team. The neoadjuvant chemoradiotherapy significantly reduced the local recurrence rate of LARC, but did not affect the occurrence of distant metastases and overall survival. Total neoadjuvant therapy (TNT), by strengthening the intensity of chemotherapy and extending the time from radiotherapy to surgery, can improve the tumor response rate as well as disease-free survival rate and metastasis-free survival rate. It offers advantages such as enhancing the compliance with chemotherapy, maximizing tumor regression, improving survival and increasing the chance of organ preservation. TNT is a promising treatment model for LARC patients with high risk of distant metastasis or strong desire for organ preservation. With the application of immunotherapy in the field of TNT, the mode of TNT continues to expand. And the exploration of therapeutic predictive markers will help to provide a personalized treatment for patients.

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis (RCLM). Methods The clinical data of young RCLM patients at 45 years or under (n=40, as younger patient group) in Peking University First Hospital from January 2016 to January 2021 were reviewed, meanwhile, elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio. Proportions of categorical variables were compared between young patients and old patients. The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy. Results One hundred and twenty-two RCLM patients were identified, the 1-, 3- and 5-year survival rates of young patient group were 97.5%, 47.5%, 15.0%, those of elder patient group were 84.1%, 26.8%, 9.8%, respectively. The differences in BMI (P=0.008), primary tumor with obstruction and bleeding (P=0.006), synchronous rectal cancer liver metastases (P=0.005), the maximum diameter of liver metastasis >3 cm (P=0.019) were statistically significant between the two groups. And univariate and multivariate analyses showed that age (P=0.003), N stage (P=0.007), local therapy for liver metastases (P=0.047) and the maximum diameter of liver metastasis (P=0.030) were independent risk factors for influencing the prognosis of RCLM patients; curative resection or not of primary tumor (P=0.035) and the maximum diameter of liver metastasis (P=0.041) were independent risk factors for influencing the prognosis of young RCLM patients. Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients (log-rank P=0.000). Conclusions Although with later staging of initial tumor station, young RCLM patients may obtain better survival benefit compared with old patients. Higher degree of lymph node metastasis, local therapy for liver metastases and the maximum diameter of liver metastasis >3 cm indicates poor prognosis in RCLM patients, and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients. Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.