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.

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.

Objective To evaluate the value of GeneXpert MTB/RIF Ultra (Xpert Ultra) in the early and rapid diagnosis of sputum and bronchoalveolar lavage fluid (BALF) samples in patients with smeared negative tuberculosis. Methods A total of 93 patients with sputum smear-negative suspected pulmonary tuberculosis who were admitted to Shandong Public Health Clinical Center from May 2020 to December 2021 were included in this study. Among them, 57 patients were clinically diagnosed as sputum smear-negative pulmonary tuberculosis and 36 patients were non-pulmonary tuberculosis. Sputum and BALF samples were collected from all patients, and Xpert Ultra, GeneXpert MTB/RIF (Xpert), BACTEC MGIT 960 culture (MGIT 960 culture) were performed. To evaluate the sensitivity, specificity and coincidence rate of various detection methods and their combined detection of sputum and bronchoalveolar lavage fluid samples in the diagnosis of smeared negative pulmonary tuberculosis. Results Taking clinical diagnosis as the reference standard, the sensitivity of sputum samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert [56.14% (32/57) vs. 36.84% (21/57), P=0.039] and MGIT 960 culture [56.14% (32/57) vs. 33.33% (19/57), P=0.014]. The sensitivity of BALF samples detected by Xpert Ultra for the diagnosis of smeared negative pulmonary tuberculosis was significantly higher than that of Xpert [75.44% (43/57) vs. 56.14% (32/57),P=0.030] and MGIT 960 culture [75.44% (43/57) vs. 38.60% (22/57), P<0.01]. Three different methods of testing sputum samples, the area under the receiver operating characteristic curve (AUC) was the combination of the three elements (0.807)>Xpert Ultra+Xpert (0.798)>Xpert Ultra+MGIT 960 culture (0.789)>Xpert Ultra method (0.781)>Xpert (0.684)>MGIT 960 culture (0.667);Samples of BALF were examined, the AUC was the combination of the three elements (0.895)=Xpert Ultra+Xpert (0.895)>Xpert Ultra+MGIT 960 culture (0.877)=Xpert Ultra method (0.877)>Xpert (0.781)>culture method (0.693). Rifampicin resistance was not detected in the enrolled samples by the three detection methods. Conclusions Xpert Ultra has high clinical application value in the early and rapid diagnosis of smeared negative pulmonary tuberculosis, and the sensitivity of Xpert Ultra in the detection of BALF is higher than that of sputum sample, so the BALF sample is recommended as prior selection.

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.

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 observe the changes in depression-like behavior and cAMP-PKA-CREB-BDNF signaling pathway in the hippocampus of rats with mild brain blast injury (mbTBI) caused by blast shock wave, and to explore the mechanism of neurological dysfunction caused by mbTBI. Methods 44 male SD rats were randomly divided into control group and model group, 22 in each group. The rats in the model group were placed in a gridded iron cage, with the head facing the explosion center and fixed on the ground 15 m away from the explosion center in a fan shape. At the same time, the shock wave intensity at the location of the rats was detected. After the explosion, 7 rats in each group were randomly selected and fed in separate cages. Open field test and elevated plus maze test were used to evaluate the depression-like behavior of rats at 7, 14 and 28 d after exposure. The remaining rats in each group were randomly sacrificed at 7, 14 and 28 d after exposure. The hippocampus was removed and protein extracted. Western blotting was used to detect the relative expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (p-CREB), brain-derived neurotrophic factor (BDNF) and oncogenic protein c-FOS. Results After the explosion test, all the rats in the model group survived, but within 24 hours, they were apathetic, slow in action and poor in appetite. After 72 hours, the above symptoms gradually eased. There was no significant difference in body weight between the two groups at each time point (P>0.05). The results of behavioral experiments showed that compared with the control group, the total moving distance, the residence time in the central area, the number of times and the proportion of time entering the open arm of the model group were significantly reduced at 14 d after the explosion test (P<0.05). The results of Western blotting showed that compared with the control group, the expression levels of PKA, CREB, pCREB and BDNF protein in the model group were significantly decreased at 7, 14 and 28 d after explosion test (P<0.05). Compared with the control group, the expression of cAMP and c-FOS in the model group was significantly decreased at 7 and 14 d after the explosion test (P<0.05), and there was no significant difference between the two groups at 28 d(P>0.05). Compared with 7 and 14 d after the explosion test, the expression levels of PKA, CREB and BDNF in the model group were significantly increased at 28 d after the test (P<0.05). Conclusion Single blast shock wave exposure can cause depression-like behavior changes in rats, which may be related to the down-regulation of the cAMP-PKA-CREB-BDNF signaling pathway.

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 clinical effect of non-invasive prenatal testing (NIPT) by analyzing the efficiency of fetal chromosomal aneuploidy screening in Beijing. Methods The clinical data of 133 899 pregnant women, who underwent NIPT in eight prenatal diagnosis institutions of Beijing from January 2019 to December 2020, were collected and retrospectively analyzed. The test indications, results and prenatal diagnosis results were recorded. The positive rate of all pregnant women was calculated according to the test indications; According to the test results, it can be divided into trisomy 21 syndrome, trisomy 18 syndrome, trisomy 13 syndrome, sex chromosome abnormality, and other chromosome abnormalities. The prenatal diagnosis rate, positive rate, positive predictive value (PPV), sensitivity and specificity were calculated. Results Among the NIPT screening indicators, the detection rate of elderly pregnant women was the highest, accounting for 34.0% (45 509/133 899), followed by voluntary requirements, accounting for 32.7% (43 860/133 899). There were 1647 cases with high risk of NIPT, the positive rate was 1.2% (1647/133 899), and the positive rate of NT thickening and ultrasound structure abnormal were the highest in pregnant women. One thousand three hundred and forty-eight cases received prenatal diagnosis. The highest prenatal diagnostic rate was trisomy 18 reached to 91.5% (130/142), the lowest was the rate of sex chromosome abnormality reached to 76.4% (488/639). The overall prenatal diagnostic rate was 81.8% (1348/1647). The positive rates of trisomy 21, trisomy 18, trisomy 13, sex chromosome abnormality and other chromosomes abnormality were 0.2% (318/133 899), 0.1% (142/133 899), 0.1% (77/133 899), 0.5%(639/133 899) and 0.4% (471/133 899), respectively. The positive predictive values were 71.1% (226/318), 38.0% (54/142), 18.2%(14/77), 31.3% (200/639) and 17.8% (84/471), respectively. The sensitivity of trisomy 21, trisomy 18 and trisomy 13 was 98.7%, 96.4% and 100.0%, and all the specificity of was 99.9%. Conclusions The NIPT had high sensitivity and specificity but also still had the limitations of false positive and false negative. Therefore, prenatal diagnosis should be carried out for NIPT high-risk pregnant women, and it is important to strengthen the genetic counseling before and after testing.

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 investigate the changes of posterior chamber intraocular lens (ICL-V4c) implantation on retinal and choroid thickness, retinal blood flow density in the macular area, and optic disc in ultra-high myopia using optical coherence tomography angiography (OCTA). Methods From April 2020 to May 2021, 15 patients (30 eyes) with binocular equivalent spherical lens (SE) ≥–10.00 D in Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled. All eyes had undergone the ICL-V4c treatment. We observed the visual acuity and intraocular pressure at the following time points: before the operation, 2-hour, 1-week, 1-month, and 9-month post-operation. OCTA was used to monitor the changes in retinal and choroid thickness in the macular area as well as retinal blood flow density around the macular area and optic disc. Results There was no statistically significant difference between uncorrected viusal acuity postoperative and best corrected viusal acuity preoperative at each time point after surgery (P>0.05). The postoperative intraocular pressure showed a downward trend, but the difference was not statistically significant. The vault at 9-month post-surgery was significantly lower than that at 1-week post-surgery, the difference was statistically significant (P=0.002). There were no statistically significant differences in deep retinal blood flow density, retinal thickness or choroid thickness in the macular area, blood flow density in the radial capillary network around the optic disc, and nerve fiber layer thickness at each postoperative time point (P>0.05). The superficial retinal blood flow density in the four directions of upper, lower, nasal, and temporal decreased significantly 2-hour after surgery, with statistical significance (P<0.05). With the extension of time, the blood flow density in each area increased significantly, and there was no statistical difference compared with that before surgery (P>0.05). Conclusion OCTA observation showed that ICL-V4c implantation had an effect on the superficial retinal blood flow density in the early stage of ultra-high myopia but would restored to the preoperative level during the time, and had no effect on the retinal choroid thickness in the remnant macular area, the blood flow density of the capillary network around the optic disc and the thickness of the nerve fiber layer.

Objective To analyze the clinical features and pathological diagnosis of 3 cases of pineal region papillary tumor(PTPR), and review the related literature. Methods Three cases of PTPR patients were collected in the First Affiliated Hospital of Xinjiang Medical University from January 2012 to March 2021, and studied by HE staining and immunohistochemistry to observe its histological morphology and immunohistochemical phenotype. Combined with reviewing the relevant literature to understand the molecular characteristics of the disease and find potential therapeutic targets. Results The first symptom in the three PTPR patients were headache and intracranial hypertension. Histological examination showed that PTPR tumor cells formed a single-layer or stratified papillary structure surrounding the vascular. The distribution of the tumor cells had polarity, with more abundant cells near the vascular. Immunohistochemistry reveals strong reactivity for AE1/AE3, CAM5.2, cytokeratin 18 (CK18) and pair box 8(PAX8). The staining for vimentin (VIM) showed positive which is especially dense in cells near the vessel. The staining for nervous marker S-100 displayed diffuse positive in two cases while focal positive in the other one, while both glial fibrillary acidic protein(GFAP) and oligodendrocyte transcription-2 (OLIG-2) were negative in all the three cases. PTEN expression deficiency and p-Akt positive expression in the three cases. Literature reviews obtained 9 reports relevant to the molecular mechanism of PTPR, with 7 of them using genomic hybridization to detect chromosomal alterations in 29(29/62) patients, among which chromosome 10 loss and chromosome 8 gain were observed in 96.6%(28/29) cases and 57.1%(16/28) cases, respectively. Conclusions Exhibiting specific papillary structures, PTPR displayed specific immunohistochemical characteristics, which is helpful for diagnosis. PTEN protein deletion and positive expression of p-Akt and PAX8 suggested that PAX8, PTEN and PI3K/Akt/mTOR signal pathways played a potential role in the occurrence and development of PTPR and may become potential therapy targets.

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.

Type 2 diabetes mellitus (T2DM) is often associated with anxiety disorders. It has been found that there is a complex pathogenic interaction between T2DM and anxiety disorders, but little is known about the mechanism of their overlap.Both T2DM and anxiety disorders are characterized by changes in the function of the central nervous system, share a common biological mechanism on neurobiochemistry, brain-derived neurotrophic factor (BDNF), immune inflammation, and hypothalamus-pituitary-adrenal (HPA) axis, but it is not clear whether it is the mechanism of overlap. The present article mainly reviews whether there is a correlation between T2DM and anxiety disorders in neurobiochemical-related mechanisms such as γ-aminobutyric acid(GABA), glutamate (Glu), 5-hydroxytryptamine (5-HT), dopamine (DA), BDNF, immune inflammation, and HPA axis, in order to explore the potential neuropathophysiological overlap mechanism of T2DM and anxiety disorders and to provide a reference for the treatment of the comorbidity.

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.

Monogenic diabetes is a type of diabetes characterized by single gene mutation. Due to its heterogeneity and overlap with type 1 and type 2 diabetes, it is difficult to be accurately diagnosed clinically. Correct diagnosis is essential for certain types of monogenic diabetes, however, there is still a lack of simple clinical criteria for selecting patients for genetic testing or even interpreting the results of genetic testing. The classification of monogenic diabetes (including maturity onset diabetes of the young, neonatal diabetes mellitus, mitochondrial diabetes mellitus and syndromic diabetes mellitus) and the clinical diagnosis and corresponding treatment methods of monogenic diabetes based on the new generation sequencing and clinical characteristics have been reviewed in present paper for providing theoretical basis for clinical diagnosis of physicians as well as help to individualize the treatment of patients with monogenic diabetes.

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.

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.

Since the outbreak of the coronavirus disease 2019 (COVID-19), machine learning has been widely used in forecasting the epidemic trend of COVID-19, screening and tracking high-risk people, early diagnosis and monitoring of patients, etc., which has greatly improved the efficiency of information processing during the epidemic period and provided efficient decision support for clinicians. However, due to the different data types and scales and training methods used to develop models, machine learning that perform diagnosis or prognosis tasks also have different limitations. This review introduces the application of machine learning in the diagnosis and prognosis of COVID-19 from the aspects of machine learning combined with imaging data, laboratory results, and the model trained by integrating these two aspects, trying to provide more practical ways for machine learning in training and application.