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.