The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

Objective:To analyze the medication characteristics of ancient prescriptions for pediatric epilepsy (PE) through data mining; To summarize the compatibility law; To provide a reference for the treatment selection of Chinese materia medica and the development of patent drugs related to PE in clinic.Methods:Those with definite composition, dosage and efficacy for the treatment of PE was screened from the data of TCM prescription designed by Institute of Traditional Chinese Medicine Information, China Academy of Traditional Chinese Medicine. Excel 2013 was used to analyze the frequency of Chinese materia medica and its flavor and meridian tropism in the included prescriptions. The arules package in R 3.6.3 was used for association analysis based on Apriori algorithm. The sankey package and ggraph package of R 3.6.3 were used to draw the network diagram of the property, taste, meridian tropism and association rules of high-frequency Chinese medicine, so as to realize data visualization.Results:A total of 360 ancient prescriptions for the treatment of PE were included, and the dosage form was mainly pills. Most of the prescriptions were composed of 1 to 10 kinds of Chinese materia medica, with a total of 192 (53.33%, 192/360) prescriptions. 152 kinds of Chinese materia medica were included. The most commonly used types of Chinese materia medica were Glycyrrhizae Radix et Rhizoma, Moschus, Saposhnikoviae Radix, Gastrodiae Rhizoma, and Aconiti Lateralis Radix Praeparata. The properties of high-frequency Chinese materia medica (frequency≥30) were characterized by warm and mild, and the tastes were mainly pungent, bitter and sweet, and the meridians were mainly spleen and liver meridians. Through Apriori association analysis, the commonly used combination drugs were Bovis Calculus-Moschus, Ginseng Radix et Rhizoma-Poria and Saposheikovize Radix-Glycyrrhizae Radix et Rhizoma. Similarly, the commonly used triple drugs included Gastrodiae Rhizoma-Aconiti Lateralis Radix Praeparata-Bombyx Batryticatus, Poria-Glycyrrhizae Radix et Rhizoma-Ginseng Radix et Rhizoma, and Moschus-Bovis Calculus-Realgar.Conclusions:The ancient prescriptions for the treatment of PE is mainly composed of wind-calming, resuscitation and tonifying drug. The core prescription ideas of the ancient prescriptions are as follows: dispelling phlegm and dispelling wind, warming the meridian and dispelling yang, resuscitating and relieving spasms, clearing heat and reducing depression, and tonifying qi and blood.

Objective To construct and validate a risk prediction model for enteral nutrition feeding intolerance (FI) in patients with severe cerebral hemorrhage based on machine learning algorithms. Methods The clinical data of 485 patients with cerebral hemorrhage admitted to the neurological intensive care unit of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2020 to December 2022 were retrospectively analyzed. The patients were randomly divided into training set (n=339) and validation set (n=146) in a 7 to 3 ratio. Five machine learning algorithms were used to construct FI risk prediction models. The receiver operating characteristic (ROC) curve was plotted, and the model with the best predictive performance was selected based on the area under the curve (AUC). A nomogram model was constructed based on the optimal model. The calibration curve and decision curve analysis (DCA) were used to evaluate the calibration and clinical net benefit of the nomogram model. Results The incidence of enteral nutrition FI in patients with severe cerebral hemorrhage was 38.4%(186/485). Among the five machine learning algorithm models, the Logistic regression model had the best predictive performance(AUC=0.88). The analysis results of the Logistic regression model showed that the use of diuretics, mechanical ventilation, Glasgow Coma Scale score ≤5, vasoactive drugs, and albumin level<35 g/L were risk factors for enteral nutrition FI in patients with severe cerebral hemorrhage. A nomogram model was further constructed based on these five risk factors. The calibration curve analysis showed that the calibration curve fitted well with the ideal curve, indicating a high calibration degree of the nomogram model. The DCA results showed that when the threshold probability was 5% to 73%, the application of the nomogram model for screening could clinically benefit patients. Conclusion The construction of a nomogram model for predicting the risk of enteral nutrition FI in patients with severe cerebral hemorrhage based on machine learning methods can help to early screen high-risk patients for enteral nutrition FI and timely formulate preventive measures, thereby reducing the incidence of enteral nutrition FI in patients with severe cerebral hemorrhage.

Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.

Polysaccharide is a recognized immunomodulator that has been shown to have inhibitory effects on a variety of cancer cells and has the potential to be developed as an anti-cancer drug. Pancreatic cancer， one of the cancers with the highest mortality rate， is treated with long-term chemotherapeutic drugs and is prone to a variety of side effects such as immune deficiency， fatigue， and neurological lesions. The polysaccharide anti-pancreatic cancer research landscape both domestically and internationally is summarized in this publication. By regulating nuclear factor-κB， Hippo-Yes-associated protein， integrin and other signaling pathways， polysaccharide components play an anti-pancreatic cancer role by multi-target ways， such as inducing apoptosis and autophagy， inhibiting proliferation， migration and invasion of cancer cells， and regulating the cancer cell cycle.

Objective:To investigate the familial inheritances, clinical features, treatments and outcomes of familial Waldenstrom macroglobulinemia (WM) patients.Methods:The clinical manifestations, laboratory examinations, diagnosis and treatments, and follow-up data of 6 familial WM patients who were admitted to Yancheng No.1 People's Hospital from June 2002 to July 2019 were retrospectively analyzed, and the literature was reviewed.Results:Among 6 WM patients, 4 patients had dizziness and fatigue at the onset, 1 patient had recurrent low-grade fever and abnormal sweating as the first manifestations, 1 patient was hospitalized due to pulmonary infection, and WM was found later. Two brothers of the patients were diagnosed with WM, another 2 brothers of the patients had IgM-type monoclonal gammopathy of undetermined significance (MGUS) during the physical examination. All the 6 patients were middle-aged/elderly men, with a median age of 63 years old (51-70 years old). The median follow-up time were 71.5 months (4-217 months), and by the end of the follow-up (June 2020), 2 cases died of pulmonary infection, and 1 of them developed acute myeloid leukemia; the other 4 cases were in regular chemotherapy. Two IgM-MGUS patients were followed up without symptoms.Conclusions:WM patients have familial aggregation, and their clinical manifestations are highly heterogeneous. Patients with family history may have poor prognosis. It is necessary to strengthen the awareness of WM and family history screening.

Objective:To investigate the effect of fluid resuscitation and circulatory support, directed by different target mean arterial pressure (MAP), on abdominal blood flow, gastrointestinal function and inflammatory response in septic shock patients with hypertension.Methods:A prospective randomized controlled study was conducted. Hypertensive patients with septic shock admitted to the department of intensive care unit (ICU) of Liuzhou People's Hospital from January 1, 2019 to May 31, 2020 were enrolled. Patients were randomly divided into the low MAP groups (low standard group, LS group) or high MAP group (high standard group, HS group). According to the Surviving Sepsis Campaign Guidelines in 2016 and the updated guideline in 2018, all patients were given treatment of primary disease, fluid resuscitation, supportive management. The target MAP was 65-70 mmHg (1 mmHg = 0.133 kPa) in LS group, and was 75-80 mmHg in HS group. Acute gastrointestinal function injury (AGI) classification was performed on the 1st, 3rd and 7th day. The mean flow rate (Vm) and resistance index (RI) of superior mesenteric artery were evaluated using ultrasound, and the gastrointestinal function was dynamically evaluated using the modified single section ultrasonic gastric antrum method. The gastric antrum movement index (MI) and gastric empaging time (GET) were recorded. The levels of inflammatory markers in serum were detected by enzyme linked immunosorbent assay (ELISA), such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), procalcitonin (PCT) and vascular endothelial growth factor (VEGF). The target MAP, the days of use of vasopressors and the amount of fluid resuscitation were recorded.Results:A total of 208 hypertensive patients with septic shock were enrolled, including 109 in the LS group and 99 in the HS group. There were no significant differences in gender, age, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score between the two groups when diagnosed. After treatment, there was no significant difference in AGI classification between the LS group and HS group on the 1st day. On the 3rd and 7th day, there were statistical differences between the two groups (3rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 25.69%, 56.88%, 11.93%, 5.50% in LS group, 15.15%, 54.55%, 25.25%, 5.05% in HS group, respectively, χ 2 = 7.900, P = 0.048; 7rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 44.96%, 49.54%, 3.67%, 1.83% in LS group, 31.31%, 52.53%, 11.11%, 5.05% in HS group, respectively, χ 2 = 8.178, P = 0.042). The Vm of superior mesenteric artery was higher and the RI was lower in the LS group than those in the HS group on day 1, 3 and 7 [Vm (cm/s): 21.72±3.02 vs. 19.50±2.83, 20.42±2.62 vs. 17.02±1.99, 26.52±2.70 vs. 22.47±4.03; RI: 0.86±0.05 vs. 0.92±0.04, 0.87±0.05 vs. 0.95±0.05, 0.81±0.03 vs. 0.85±0.03, all P < 0.01]. The MI was higher and the GET was shorter in the LS group than those in the HS group on day 3 and day 7 [MI: 3.00±0.33 vs. 2.60±0.29, 4.50±0.51 vs. 3.90±0.33; GET (minutes): 86.01±19.78 vs. 100.99±25.01, 71.00±16.37 vs. 84.98±20.18, all P < 0.01]. In addition, the levels of serum TNF-α, IL-6, PCT, VEGF were lower in the LS group than those in the HS group after 3 days of treatment [TNF-α (ng/L): 147.05±28.32 vs. 256.99±27.04, IL-6 (ng/L): 762.99±57.83 vs. 1 112.30±118.32, PCT (μg/L): 37.00±5.58 vs. 56.00±12.36, VEGF (ng/L): 123.00±19.78 vs. 167.01±21.55, all P < 0.05]. The target MAP was maintained at (68.02±4.71) mmHg in LS group, and (79.04±3.04) mmHg in HS group. The difference between the two groups was statistically significant ( P < 0.01). Compared with the HS group, the days of using vasopressors was shorter in LS group (days: 3.50±1.27 vs. 4.55±1.47), and the amountof fluid was reduced significantly (mL: 1 602.29±275.49 vs. 2 000.30±272.59, both P < 0.01). Conclusion:Maintaining a low target mean arterial pressure (65-70 mmHg) in hypertensive patients with septic shock can improve blood supply of superior mesenteric artery, protect the gastrointestinal function, reduce the level of inflammatory factors, and diminish the duration of using vasopressors and the amount of fluid.

The incidence and mortality of lung cancer ranked the first in China. China had 787, 000 new cases of lung cancer in 2015, and a majority of these patients with advanced lung cancer. With the development and popularization of high-resolution computed tomography, more and more early-stage lung adenocarcinomas are found in screening. The imaging finding of early-stage lung adenocarcinomas often manifests as part solid nodule (PSN) containing ground glass opacity (GGO). Although the imaging manifestation of the nodules can′t accurately predict the pathologic type of nodules, the parts of solid nodule and GGO still have some pathologic indications, and the prognostic evaluation effect of the maximum diameter of PSN is superior to that of the whole nodule. With the development of the molecular radiography and molecular pathology, the relationship of imaging manifestation of the PSN and metastasis were focused on. Some PSNs with special nature are more active and rapidly progressed than the pure GGOs. While compared to the pure solid nodules, the aggressiveness of PSNs are insufficient, with lower metastatic rates of lymph node and better prognoses. Currently, international acknowledge recommends to take active intervention measure for PSNs which are highly suspected to be malignant. We focus on the diagnosis and treatment of PSNs, systemically depict their staging, follow-up, surgical treatment, gene detection and immunotherapy.

Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinfor-matic tool for researchers to specifically identify such feature pairs. Here, we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3306 feature pairs in 16 human cell types, we reveal a dual role of CCCTC-binding factor (CTCF) in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, CTCF is required for the active marker H3K27ac in cell types requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity. The code for MACMIC is available at https://github.com/bxia888/MACMIC.

The incidence and mortality of lung cancer ranked the first in China. China had 787, 000 new cases of lung cancer in 2015, and a majority of these patients with advanced lung cancer. With the development and popularization of high-resolution computed tomography, more and more early-stage lung adenocarcinomas are found in screening. The imaging finding of early-stage lung adenocarcinomas often manifests as part solid nodule (PSN) containing ground glass opacity (GGO). Although the imaging manifestation of the nodules can′t accurately predict the pathologic type of nodules, the parts of solid nodule and GGO still have some pathologic indications, and the prognostic evaluation effect of the maximum diameter of PSN is superior to that of the whole nodule. With the development of the molecular radiography and molecular pathology, the relationship of imaging manifestation of the PSN and metastasis were focused on. Some PSNs with special nature are more active and rapidly progressed than the pure GGOs. While compared to the pure solid nodules, the aggressiveness of PSNs are insufficient, with lower metastatic rates of lymph node and better prognoses. Currently, international acknowledge recommends to take active intervention measure for PSNs which are highly suspected to be malignant. We focus on the diagnosis and treatment of PSNs, systemically depict their staging, follow-up, surgical treatment, gene detection and immunotherapy.