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 effect of glycyrrhizic acid (GA) on the inflammatory and fibrotic factors in high glucose-induced glomerular mesangial cells (SV40 MES13). Methods Cultured mouse SV40 MES13 were divided into normal group (NG, 5.6 mmol/L glucose), high glucose group (30 mmol/L glucose) and HG+GA group (30 mmol/L glucose+200 μmol/L GA). The expression levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8 and α-smooth muscle actin (α-SMA) in different groups were detected by Western blotting. The fluorescence intensity of IL-1β, TNF-α and α-SMA in different groups were detected by immunofluorescence. The levels of IL-1β, TNF-α, IL-6 and IL-8 in the culture supernatant of different populations were detected by enzyme-linked immunosorbent assay (ELISA). Results The protein expressions of IL-1β, TNF-α, IL-6, IL-8 and α-SMA in HG group were significantly higher than those in NG group (P<0.01); Compared with HG group, the protein expression levels of IL-1β, TNF-α, IL-6, IL-8 and α-SMA decreased significantly in HG+GA group (P<0.05). The fluorescence intensity of inflammatory cytokines IL-1β, TNF-α and α-SMA increased in HG group than those in NG group (P<0.05); While compared with the HG group, the fluorescence intensity of IL-1β, TNF-α and α-SMA in HG+GA group decreased markedly (P<0.05). The experimental results of ELISA showed that compared with NG group, the levels of IL-1β, IL-6, TNF-α and IL-8 in cell supernatent increased in HG group (P<0.01); while the levels of IL-1β, TNF-α, IL-6, IL-8 in HG+GA group significantly lower than those in HG group (P<0.05). Conclusion Glycyrrhizic acid has certain inhibitory effect on high glucose-induced inflammatory factors and fibrotic factors in glomerular mesangial cells, which may play an important role in prevention of diabetic nephropathy.

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.

When refractory diarrhea comes on, it greatly affects the life and daily work of patients, and there is no unified treatment. Patients with refractory diarrhea have varying degrees of intestinal flora disorder, so rebuilding the intestinal micro ecosystem may be an effective way to treat refractory diarrhea. Fecal microbiota transplantation (FMT) has the potential to be an effective treatment for refractory diarrhea as a therapy that reconstructs normal intestinal flora. In recent years, FMT has been applied to the treatment of some refractory diarrhea related to intestinal flora imbalance, such as recurrent clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, and has achieved good results, but some problems have not been properly solved so far. This article reviews the mechanism of action of FMT in the treatment of refractory diarrhea, its clinical application, research progress and current problems.

Cholesterol metabolism is a hot topic in exploration of cancer treatment in recent years, and its complex mechanism of action potentially lays a molecular foundation related to lipid-cancer. However, most studies focus only on cholesterol as a product to understand and analyze the progress of cancer, ignoring the phased effects of related derivatives, regulatory proteins and immune cells in its metabolic process, so whether to find targets to regulate colorectal cancer (CRC) from the cholesterol metabolic pathway has become a research focus. This paper reviews the molecular mechanism and the role of signaling pathways in metabolic reprogramming of CRC starting from the abnormal intracellular cholesterol metabolic pathway in order to provide new ideas for the targeted cholesterol therapy of CRC.

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.

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.

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.

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.