Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

Objective: To systematically summarize and evaluate the development of update and detailed recommendations of the existing global screening guidelines in high-risk population with a family history of colorectal cancer. Methods: The words "colorectal cancer", "screening", "guideline", "consensus", "recommendations" and "family history" in Chinese and English were used as MESH terms for literature retrieval, as well as entry terms. The retrieval was performed based on China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed, Embase, Cochrane Library and Web of Science, as well as official websites. The languages of literatures were limited in Chinese and English. As of May 24, 2022, a total of 20 valid literatures had been retrieved. The basic information of the literatures and the recommendations of colorectal cancer screening for people with family history were collected and analyzed. Results: The analysis on the 20 literatures indicated that most countries/regions/institutions recommended age range of screening, screening modalities and intervals for people with family history of colorectal cancer. For the individuals who have one first-degree relative diagnosed with colorectal cancer before 60 years of age,most guidelines recommended the screening to be started at 40 years or 10 years earlier than the age when the youngest first-degree relative was diagnosed. The most commonly recommended screening modality was colonoscopy. Conclusions: Most current screening guidelines for high-risk people with family history of colorectal cancer recommend colonoscopy as the main modality. This review will provide reference for the update of screening strategies in high-risk people with family history of colorectal cancer in China, and further improve the practices of screening, early diagnosis and treatment of colorectal cancer.
Adult ; Colonoscopy ; Colorectal Neoplasms/epidemiology* ; Early Detection of Cancer ; Humans ; Mass Screening ; Risk Factors

Objective To study the effects of TYRO protein kinase-binding protein (TYROBP) deficiency on learning behavior, glia activation and pro-inflammatory cycokines, and Tau phosphorylation of a new Alzheimer's disease (AD) mouse model carrying a PSEN1 p.G378E mutation.Methods A new AD mouse model carrying PSEN1 p.G378E mutation was built based on our previously found AD family which might be ascribed to the PSEN1 mutation, and then crossed with TYROBP deficient mice to produce the heterozygous hybrid mice (PSEN1^G378E/WT; Tyrobp^+/-) and the homozygous hybrid mice (PSEN1^G378E/G378E; Tyrobp^-/-). Water maze test was used to detect spatial learning and memory ability of mice. After the mice were sacrificed, the hippocampus was excised for further analysis. Immunofluorescence was used to identify the cell that expresses TYROBP and the number of microglia and astrocyte. Western blot was used to detect the expression levels of Tau and phosphorylated Tau (p-Tau), and ELISA to measure the levels of pro-inflammatory cytokines. Results Our results showed that TYROBP specifically expressed in the microglia of mouse hippocampus. Absence of TYROBP in PSEN1^G378E mutation mouse model prevented the deterioration of learning behavior, decreased the numbers of microglia and astrocytes, and the levels of interleukin-6, interleukin-1β and tumor necrosis factor-α in the hippocampus (all P < 0.05). The ratios of AT8/Tau5, PHF1/Tau5, pT181/Tau5, pT231/Tau5 and p-ERK/ERK were all higher in homozygous hybrid mice (PSEN1^G378E/G378E; Tyrobp^-/- mice) compared with PSEN1^G378E/G378E mice (all P < 0.05). Conclusions TYROBP deficiency might play a protective role in the modulation of neuroinflammation of AD. However, the relationship between neuroinflammation processes involving microglia and astrocyte activation, and release of pro-inflammatory cytokines, and p-Tau pathology needs further study.
Mice ; Animals ; Alzheimer Disease/genetics* ; Neuroinflammatory Diseases ; Hippocampus/pathology* ; Mutation ; Cytokines/pharmacology* ; Disease Models, Animal ; tau Proteins/pharmacology* ; Amyloid beta-Peptides/metabolism* ; Adaptor Proteins, Signal Transducing/pharmacology*

Objective:To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea.Methods:Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient’s.Results:A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion:Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.

Uterine leiomyosarcoma is an uncommon malignant neoplasm of smooth muscle origination and is associated with a poor prognosis. We report two cases of uterine leiomyosarcoma that presented with pulmonary metastases. 2-deoxy-2-(¹⁸F)fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) was performed to identify the primary carcinoma and found the focus located in the uterus. The follow-up magnetic resonance imaging (MRI) confirmed the diagnosis was uterine leiomyosarcoma.
Adult ; Female ; Fluorodeoxyglucose F18 ; Humans ; Leiomyosarcoma ; diagnosis ; Magnetic Resonance Imaging ; methods ; Middle Aged ; Positron-Emission Tomography ; methods ; Tomography, X-Ray Computed ; methods ; Uterine Neoplasms ; diagnosis

OBJECTIVETo investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma.

METHODSSixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody.

RESULTSThe overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01).

CONCLUSIONTAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.

Abdomen ; diagnostic imaging ; Adult ; Aged ; Female ; Humans ; Male ; Microvessels ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; diagnostic imaging ; Stomach Neoplasms ; diagnostic imaging ; pathology ; Ultrasonography, Doppler, Color ; methods