Immunotherapy has become one of the hopes to ultimately defeat cancer after radiotherapy, chemotherapy and targeted therapy, and tumor-associated antigen is an important target in immunotherapy. As an important member of the melanoma associated antigen-A (MAGE-A) subfamily, MAGE-A4 is highly expressed in various tumor tissues and low expressed in normal tissues except testis and placenta. It is involved in the regulation of cell functions and has important roles in regulating cell cycle, inducing cell differentiation and growth, and participating in epithelial-mesenchymal transformation, which is closely related to the tumorigenesis, progression, metastasis and prognosis. The latest study shows that the phase Ⅱ clinical study of T cell receptor-transgenic T (TCR-T) immunotherapy based on MAGE-A4 target is being carried out. The results of phase Ⅰ study showed that the overall response rate (ORR) was 23.7% and the disease stability was 47.4%, suggesting that TCR-T immunotherapy based on MAGE-A4 target has good clinical application value. This paper summarizes the structure and biological function of MAGE-A4, the latest research progress of various solid tumors and its clinical application, aiming to provide theoretical basis for clinical transformation and immune-targeted therapy of MAGE-A4.

Objective To determine the diversity between the different types of pulmonary tuberculosis, a retrospective analysis was made on the characteristics of medical history, blood indicators and the characteristics of peripheral T cell subsets of these patients. Methods The data of 283 pulmonary tuberculosis patients with full information were analyzed in the Eighth Medical Center of Chinese PLA General Hospital from January 2018 to December 2021, who had definite diagnosis, neither diabetes nor drug resistance, and were all on the initial treatment. The patients were divided into four groups: secondary pulmonary tuberculosis group (PTB group, 186 cases), tracheal and bronchial tuberculosis group (BTB group, 23 cases), tuberculous pleurisy group (TBP group, 42 cases) and hematogenous disseminated pulmonary tuberculosis group (DTB group, 32 cases). The patients' general conditions, medical history characteristics, laboratory indicators and T cell subsets, etc. were analyzed comparatively. Results There were no statistical differences in the age, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocyte count, lymphocyte count and hemoglobin level of patients between PTB group, BTB group, TBP group and DTB group(P>0.05). Compared with other groups, the proportion of men (34.8%) and the smoking rate (8.8%) were lower, and the disease course was longer (only 39.1% for the patients less than 3 months) in BTB group (P<0.05); the platelet count [308.00(242.00, 432.75.00)×10⁹/L] and carbohydrate antigen 125 (CA125) level [69.10(40.94, 185.40) U/ml] were higher, the albumin level[34.50(29.60, 39.20) g/L] was lower, and the disease course was shorter (88.1% for the patients less than 3 months) in TBP group;the NK cell count [70.00(33.50, 218.50) cells/μl] and NK cell percentage [7.09%(4.38%, 11.87%)] were lower in DTB group;the differences were statistically significant (P<0.05). Conclusions Male patients are more likely to suffer from TBP and female patients are more likely to suffer from BTB. Platelet counts and CA125 level are higher in patients with TBP, while the counts and proportion of NK cells are lower in patients with DTB.

Diabetic nephropathy (DN) is a chronic microvascular disease mainly secondary to diabetes. Its pathogenesis is affected by gene polymorphism, environmental factors, and so on. More and more studies have shown that epigenetic regulation mechanism without gene sequence changes plays an important role in occurrence and development of DN. The epigenetic regulation mechanism changes dynamically with the change of the surrounding environment. Transient environmental change, such as short-term high glucose, can lead to epigenetic regulation mechanism changes, affect histone exposed amino acid residue modification, DNA methylation level, etc., regulate the expression of related genes, and eventually promote the pathophysiological changes such as inflammation, hyperplasia and fibrosis. More interestingly, although the environmental stimulus disappeared, the epigenetic influence triggered by the initial stimulus still existed, with the phenomenon of "metabolic memory", suggesting that the change of epigenetic mechanism related to environmental stimulation may be the fundamental reason for the continuous progress of complications in diabetes patients, so effective intervention at the level of epigenetic mechanism also reveals new clinical therapeutic targets. The role of epigenetic regulation in the occurrence and development of DN has been reviewed in present paper, including epigenetic differences in DN, and the role of these differences-mediated signal pathway changes on kidney disease, and pay attention to the progress of epigenetic mechanism in treatment of the diseases, so as to provide a basis for clinical diagnosis and treatment of DN through epigenetic mechanism.

Objective To analyze the possible risk factors for postoperative acute kidney injury (AKI) in patients undergoing non-cardiac surgery under general anesthesia. Methods Based on anesthesia and perioperative medical specialty data platform, the clinical data were retrospectively collected of patients with general anesthesia grade Ⅲ-Ⅳ non-cardiac surgery who were admitted to the Guangdong Second Provincial General Hospital from January 2019 to May 2021. According to the AKI diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO), 205 patients with relatively complete data were screened and set as postoperative AKI group, and 251 patients without postoperative AKI were set as non-postoperative AKI group.Univariate and multivariate logistic regression analysis were performed to identify the risk factors of postoperative AKI. Results Compared with non-postoperative AKI group, patients in postoperative AKI group had lower preoperative erythrocytes, hemoglobin, albumin and initial mean arterial pressure (P<0.05). Preoperative creatinine, D-dimer, C-reactive protein (CRP), fibrinogen, total intraoperative output and American Society of Anesthesiologists (ASA) physical status classification were higher (P<0.05).Multivariate logistic regression analysis showed that preoperative hemoglobin, initial mean arterial pressure and preoperative creatinine level were independent risk factors for postoperative AKI (OR=0.958, 0.976 and 1.021 respectively, P<0.05). Conclusion The occurrence of postoperative AKI in patients undergoing non-cardiac surgery of grade III-IV under general anesthesia is related to preoperative hemoglobin level, preoperative creatinine level and initial mean arterial pressure, which is worth further big data research.

Objective To explore the role of interleukin-18 binding protein (IL-18BP) in alleviating cognitive dysfunction of traumatic brain injury (TBI) rats and the related mechanisms. Methods A total of 120 adult male SD rats were randomly divided into 4 groups (30 each): sham group, TBI group, TBI+IL-18BP group (administered 1.5 mg/kg IL-18BP by tail vein), and TBI+IL-18BP+ADU-S100 group (administered 1.5 mg/kg IL-18BP by tail vein, and 20 mg/kg ADU-S100 by intraperitoneal injection). The rat model of TBI was established using the free falling body method. At 30 d after modeling, cognitive function of rats was measured by Morris water maze test. The serum levels of IL-18 and IL-18BP were detected by ELISA. The integrated fluorescence intensity of GFAP, IL-18 and cleaved-caspase-3 in hippocampus were detected by immunofluorescence. The relative expression levels of stimulator of interferon genes (STING), phosphorylated TANK-binding kinase 1 (p-TBK1), TBK1, phosphorylated interferon regulating factor 3 (p-IRF3), and IRF3 in hippocampus were detected using Western blotting. Results Compared with sham group, rats in TBI, TBI+IL-18BP and TBI+IL-18BP+ADU-S100 groups had longer escape latency and decreased times of crossing the platform and reduced time of acting in the targeted quadrant (P<0.0001), with increased concentration of IL-18 and IL-18BP in the blood, enhanced fluorescence intensity of IL-18 and cleaved-caspase-3, up-regulated expression levels of STING, p-TBK1 and p-IRF3 in the hippocampus (P<0.05); Compared with TBI group, the escape latency was shortened, the times of crossing platform and the percentage of target quadrant activity time were increased in TBI+IL-18BP group (P<0.001), the concentration of serum IL-18 decreased while of serum IL-18BP increased, and the fluorescence intensity of IL-18 and cleaved-caspase-3, the expressions of STING, p-TBK1 and p-IRF3 in the hippocampus were down-regulated significantly in TBI+IL-18BP group (P<0.05); Compared with TBI+IL-18BP group, the latency was significantly prolonged, the platform crossing times remarkably reduced, the time spent in the target quadrant was considerably shortened, the concentration of serum IL-18 increased while of IL-18BP decreased, the fluorescence intensity of IL-18 and cleaved-caspase-3, the expression levels of STING, p-TBK1 and p-IRF3 in hippocampus were increased in TBI+IL-18BP+ADU-S100 group (P<0.05). Conclusion IL-18BP can improve the cognitive function of TBI rats to some extent, and its mechanism may be related to the inhibition of astrocytes apoptosis and STING/TBK1/IRF3 signaling pathway.

Objective To analyze the clinical features and gene phenotype of sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) due to TRNT1 mutation in two siblings from non-consanguineous parents. Methods The clinical data of the siblings with SIFD that were diagnosed in the department of allergy, immunology and rheumatology of Guangzhou Women and Children's Medical Center were collected. Then we detected the whole genome sequencing analysis with the peripheral blood samples of the patients and their parent. We summarize the clinical characteristics and gene analysis of 55 patients with SIFD that were concluded from the PubMed, China national knowledge internet and Wanfang databases. Results The proband was a 15-year-old girl, she presented with recurrent fever and elevated inflammatory markers since she was 8 months of age. After 1 year-old of age, she gradually developed swelling and arthralgia of the right knee, flexion deformity of arthritis, bilateral cataract, developmental delay and growth retardation. She can't talk with others, can't walk by herself and had no menstruation until now. The proband's sibling brother was 7 years old, presented with hypoimmunoglobulinemia and normal B cell counts at 3 months, which showed low immunoglobulin A but with normal immunoglobulin G and M and normal B cell counts at 2 years old. Diarrhea appeared at 4 months of age. He was hospitalized with fever, bronchopneumonia and diarrhea at 8 months of age. Since then, he was prone to recurrent fever and diarrhea. At 19 months, he developed arthritis of both knees and presented bilateral cataract at the age of 2 years. Irregular infusion of immunoglobulin was performed, swelling and pain of the knee gradually improved and the frequency of fever decreased. Now, he still presents with developmental delay and growth retardation. He can talk with people by 3-7 words short sentences, but the pronunciation is not clear. He can understand and carry out the orders of his parent. He can walk alone but with poor stability. Whole genome sequencing of the blood revealed biallelic TRNT1 heterozygous mutations, c.1056+1G>A/c.1246A>G (p.K416E). A total of 55 cases were reported in the literatures, including 21 males and 30 females, and 4 cases were not mentioned in the references. The clinical manifestations presented with repeated fever, different levels of sideroblastic anemia and immunologic abnormalities, arthritis, growth retardation, hearing abnormalities, cataracts, repeated infections, skin rashes and so on. Intravenous infusion of immunoglobulin and tumor necrosis factor-α antagonists, hematopoietic stem cell transplantation and positive symptomatic treatments may improve the prognosis. Conclusions SIFD caused by TRNT1 gene mutation is an autosomal recessive inherited disease with diverse clinical manifestations. Genetic testing of TRNT1 gene mutationis is the basis of clinical diagnosis. Clinicians should recognize the complex disease, early diagnosis and intervention can improve the quality of life for patients.

Objective To explore the preventive effect of Shengmaiyin on coagulation dysfunction of exertional heatstroke(EHS) in rat. Methods Fifteen SPF male SD rats were randomly divided into sham operation group, heatstroke group, and Shengmaiyin group (5 each group) after implantation of telemetry temperature capsule for one week. Rats in Shengmaiyin group were given Shengmaiyin at 0.02 ml/(g·d) by gavage for five days. The rats in the heatstroke group and Shengmaiyin group ran in the artificial climate chamber (40 ℃, 70% humidity). The running time and distance were recorded when the core temperature reached 42 ℃. Blood samples from the three groups of rats were collected to evaluate prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT), blood lactic acid (Lac), thrombomodulin (TM), thrombin sensitive protein-1(TSP-1), von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1). Pathological changes were examined in the liver, kidney, lung, intestine, and heart. Results When the core temperature reached 42 ℃, the running distance and running time of rats in the Shengmaiyin group were significantly longer than those in the heatstroke group [(456.3±92.3) m vs.282.8±87.5) m, P<0.05; (36.3±6.3) min vs. (21.7±7.0) min, P<0.05]. Compared with the control group, PT and APTT in the heatstroke group were significantly prolonged [(13.8±0.7) s vs. (9.9±0.7) s, P<0.05; 78.3(36.0, 120.0) s vs. 19.0(16.6, 22.5) s,P<0.05], Lac was significantly increased [(10.5±2.0) mmol/L vs. (4.0±0.7) mmol/L, P<0.05], and PLT decreased significantly[(590.3±80.2)×10⁹/L vs. (1750.3±283.0)×10⁹/L, P<0.05], plasma TM, vWF, TSP-1, and PAI-1 levels increased significantly[2.1(1.8, 2.7) ng/ml vs. 1.6(1.5±1.7) ng/ml, P<0.05; (953.1±60.0) pg/ml vs. (462.3±37.0) pg/ml, P<0.05; (78.1±19.8) ng/ml vs. (59.3±12.0) ng/ml, P<0.05; (1945.7±74.5) ng/ml vs. (1487.6±259.1) ng/ml, P<0.05]. Compared with the rats in heatstroke group, the APTT of the rats in Shengmaiyin group was significantly shortened [36.6(31.1, 46.1) s vs. 78.3(36.0, 120.0) s, P<0.05], and the PLT elevated significantly [(980.5±302.4)×10⁹/L vs. (590.3±80.2)×10⁹/L, P<0.05], plasma TM, vWF and PAI-1 levels were significantly reduced [1.7(1.6, 1.8) ng/ml vs. 2.1(1.8, 2.7) ng/ml, P<0.05; (701.6±32.0) pg/ml vs. (953.1±60.0) pg/ml,P<0.05; (1582.8±71.6) ng/ml vs. (1945.7±74.5) ng/ml, P<0.05]. Thrombosis was found in liver, kidney, lung, intestine, and heart in heat stroke group, while no appreciable thrombosis was observed in Shengmaiyin group. Conclusion Shengmaiyin can relieve vascular endothelial cell injury, reduce consumption of coagulation factors and platelets, and prevent coagulation dysfunction in rats with EHS.

Objective To evaluate the immunotherapeutic effect of Bacille Calmette-Guérin (BCG) in type 1 diabetes mellitus (T1DM) mice and explore its mechanism. Methods Fifteen SPF grade male C57BL/6 mice were randomly divided into molding group (n=10, established T1DM model by intraperitoneal injection of streptozotocin 50 mg/kg)and control group (n=5, intraperitoneal injection of equivalent amount of citric acid buffer). Ten mice with random blood glucose≥16.7 mmol/L were divided into T1DM group and BCG group (5 each). Mice in BCG group were then subcutaneously injected with 1×10⁶ cfu/mouse of BCG at an interval of 4 weeks for 2 times, and the other two groups were injected with the same dose of phosphate buffer solution (PBS). During the experimental period (13 weeks), the body weight and food consumption of mice were monitored weekly, and blood glucose levels were measured by tail vein sampling. Oral glucose tolerance test (OGTT) was used to detect the glucose regulation ability of mice after glucose load. HE staining was used to observe the pathological changes of pancreatic tissue. Pancreatic insulin level was detected by immunohistochemistry (IHC). Serum C-peptide levels were detected by enzyme linked immunosorbent assay (ELISA). Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the transcription levels of cytokines in mice spleen. The proportion of regulatory T cells (Treg) in splenocytes was detected by flow cytometry. Results After twice immunization with BCG (13-week), the blood glucose level increased significantly of mice in T1DM group than that in control group (P<0.001); while in BCG group was still higher than that in control group, but was significantly lower than that in T1DM group (P<0.01). The oral glucose tolerance test (OGTT) showed that, the blood glucose levels of mice in the three groups increased rapidly after glucose load, and began to decline at 120 min, and decreased to normal level at 180 min in control group; Compared with control group, the blood glucose levels of mice in T1DM group and BCG group also decreased after 120 min, but were still higher significantly than in control group at 180 min (P<0.001), while the blood glucose level in BCG group was lower than that in T1DM group, but the difference was not statistically significant (P>0.05). At initial immunization (5th-week), compared with control group, the percentage of weight gain decreased in T1DM group and BCG group (P<0.0001), and the food consumption increased significantly (P<0.0001); After twice immunization with BCG (13th-week), compared with control group, the percentage of weight gain in T1DM group was still lower significantly (P<0.0001), and the food consumption was significantly higher (P<0.001).Compared with T1DM group, the percentage of weight gain in BCG group increased (P<0.001), and the food consumption was lower (P<0.001), and there was no significant difference compared with control group (P>0.05). The results of HE staining showed that, compared with control group, the islets of mice in T1DM group had obvious atrophy, while the morphology of islets of mice in BCG group was similar to that in control group, and the number of cells in islets was significantly higher than that in T1DM group.The insulin immunohistochemistry (IHC) staining showed that, compared with control group, the insulin-positive area in pancreas of mice decreased significantly in T1DM group (P<0.01), and although the insulin positive area in BCG group was lower than that in control group (P<0.05), but was still significantly higher than that in T1DM group (P<0.05). ELISA test showed that the contents of serum C-peptide in T1DM group and BCG group decreased obviously than that in control group (P<0.001, P<0.05), however, the content of serum C-peptide in BCG group was significantly higher than that in T1DM group (P<0.05). qRT-PCR showed that, compared with control group, the level of cytokine mRNA in T1DM group did not change (P>0.05); Compared with T1DM group and control group, the mRNA levels of IL-2, IL-10 and transforming growth factor-β (TGF-β) were significantly increased in BCG group (P<0.0001), but there was no change in mRNA level of γ-interferon (IFN-γ) (P>0.05). The results of flow cytometry showed that compared with control group, the percentage of Treg cells in T1DM group decreased (P<0.05), while compared with T1DM group, the percentage of Treg cells in BCG group increased obviously (P<0.05), and there was no statistical difference compared with control group (P>0.05). Conclusion BCG immunotherapy could induce the increase of Treg cells, regulate autoimmune response, and promotes insulin secretion by reducing pancreatic pathological damage and restoring islet cell function, thus reducing the blood glucose level of T1DM mice.

Gut microflora (GM) or intestinal microecology (IM) is of great importance in maintaining human homeostasis and health. Cardiovascular disease (CVD) is a global health burden nowadays with high morbidity and mortality, the existing research confirmed that GM/IM metabolic imbalance is closely related to the occurrence and development of CVD, and some GM/IM metabolites can also be used as biomarkers of CVD disease, and their detection or intervention becomes a possible means of diagnosis, prevention or treatment of CVD. Clinical drug metabolism and efficacy evaluation, and superior effect screening from the GM/IM level is also a research direction of clinical pharmacology. With the implementation of the concept of precision medicine and a wide health, GM/IM whole-genome sequencing and metabolomics continue to be researched, the basic research and clinical application of GM/IM and CVD will be a hot topic in the future. The research status of the relationship between GM/IM and CVD has been reviewed in present paper for providing diagnosis and treatment ideas and related references for the prevention and treatment of CVD.

Objective To identify the epidemiological characteristics of tuberculosis in Zigong from 2018 to 2021, and to compare the epidemic situation of tuberculosis before and during the COVID-19 pandemic, so as to provide guidance for further prevention and control. Methods The data of tuberculosis cases reported in Zigong from January 1, 2018 to December 31, 2021 were derived from the "Tuberculosis Information Management System". And further descriptive epidemiological analysis was carried out based on the collected data. Results A total of 5289 tuberculosis cases were reported in Zigong from 2018 to 2021 with the range of reported incidence from 49.29/100 000 to 55.19/100 000, and the average incidence reported was 52.54/100 000. The incidence showed two peaks every year from 2018 to 2021, except for 2020 with only one peak in September. The ratio of male to female patients was 3.14:1 (4010:1279) and farmers were the main occupation of patients (56.06%). Tuberculous pleurisy was the main type of extrapulmonary tuberculosis (69.17%), and diabetes was the main type of comorbidities (74.32%), respectively. Ziliujing district showed the lowest incidence among these districts in Zigong. Newly treated patients have been the main treatment type of tuberculosis patients in Zigong in the past four years with the ratio of newly patients to retreatment patients of 14.60:1(4950:339). There were four types of patients showing high rates of consultation delays, including officers (74.29%), retreatment patients (73.75%), diagnosed (74.95%) and recommended (78.57%) due to symptoms. During the COVID-19 pandemic, while the reported incidence of tuberculosis in Zigong city has decreased, the rate of laboratory positive detection has also decreased. Conclusions Middle-aged male and farmers are still the focus of tuberculosis prevention and treatment in Zigong. The COVID-19 pandemic has little effect on the gender structure of patients. However, the COVID-19 pandemic might cause a slight increase in the number of hidden tuberculosis patients in Zigong. It is suggested to strengthen publicity, education and screening for the target population.