Objective To explore the mechanism of baicalin intervention in gastrointestinal acute graft versus host disease (aGVHD). Methods Peripheral blood mononuclear cells from patients with intestinal aGVHD and healthy volunteers were collected for high-throughput sequencing and differential mRNA enrichment analysis. The intersection of the baicalin target and differential mRNA was analyzed. CB6F1 mice were irradiated with 60Co X-rays. After irradiation,a mononuclear cell suspension (1×107 bone marrow cell+1×107 spleen cell) of BALB/cH-2d mice was injected into CB6F1 mice through the tail vein,and these mice were randomly devided into the model group and the baicalin group. 6 SPF female mice were selected as the normal group. After modeling,the baicalin group was administered 30mg/(kg·d) of baicalin by gavage,and the model and normal groups were gavaged with normal saline of equal volume. Serum cytokines were detected after 14 days,and aGVHD scores and small intestinal mucosa pathdogy scores,immunohistochemical,and immunofluorescence detection were performed. Results A total of 2,131 different mRNAs were identified from patients with intestinal aGVHD and healthy volunteers. Kyoto Encyclopedia of Genes and Genomes analysis indicated that these mRNAs enriched the TNF signaling pathway and other pathways. The baicalin target was intersected with the above differential genes,and TNF-α and IL-2 were the primary baicalin targets in the treatment of intestinal aGVHD. The aGVHD scores and small intestinal mucosal pathology scores after baicalin treatment were significantly better than those in the model group,serum TNF-α and IL-2 levels were significantly decreased,and the TNF-α and IL-2 protein expression levels in intestinal immunohistochemistry and immunofluorescence were also significantly recovered (P<0.05). Conclusion Baicalin can reduce the inflammatory infiltration and destruction of intestinal mucosa by reducing TNF-α and IL-2 production and reducing the incidence of intestinal aGVHD after transplantation.

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.
Humans ; Child ; Female ; Abnormalities, Multiple ; Blood Group Antigens ; Family ; Malformations of Cortical Development/genetics* ; Brain ; Mutation

Objective:To explore the risks of cardiovascular disease (CVD) and influencing factors in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients with long-term combination anti-retroviral therapy (cART).Methods:The baseline data from the multi-center prospective cohort of HIV/AIDS patients who received long-term cART from 2018 to 2020 were collected. cART-naive HIV/AIDS patients were matched by age and gender using the propensity score matching (PSM) as controls. Data collection adverse events of anti-human immunodeficiency virus drugs reduced model (D: A: D[R]) score, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were used to assess the 10-year CVD risk in patients with long-term cART treatment and in cART-naive patients. Logistic regression analysis was used to assess the risk factors related to high 10-year CVD risk.Results:A total of 301 HIV/AIDS patients received long-term cART and 300 cART-naive HIV/AIDS patients were included, with an average age of 39.8 years old. There were 490 male accounting for 81.5%. Based on the D: A: D [R] score, 4.3%(13/301) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 6.3%(19/300) of patients in the cART-naive group. Based on the FRS, 13.4%(36/269) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 10.6%(28/264) in the cART-naive group. Based on the ASCVD risk score, 10.4%(14/135) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥7.5%, and 13.8%(17/123) in the cART-naive group. There was no significant difference in the prevalence of high 10-years CVD risk between the long-term cART group and the cART-naive group assessed by any of risk equations (all P>0.050). By multivariate logistic regression analysis, the risk factors associated with 10-year CVD risk ≥10% assessed by D: A: D[R] model were age≥50 years, smoking, hypertension, diabetes, dyslipidemia and CD4 + T lymphocyte count <200×10 6 cells/L (adjusted odds ratio ( AOR)=697.48, 4 622.28, 23.11, 25.95, 27.72 and 18.25, respectively, all P<0.010). The risk factors associated with 10-year CVD risk ≥10% assessed by FRS were age≥50 years, male, smoking, hypertension, diabetes and dyslipidemia ( AOR=53.51, 4.52, 36.93, 36.77, 6.15 and 3.84, respectively, all P<0.050). The risk factors associated with 10-year CVD risk ≥7.5% assessed by ASCVD risk score were age≥50 years, male, smoking, hypertension, diabetes ( AOR=18.48, 14.11, 14.81, 13.42 and 12.41, respectively, all P<0.050). Conclusions:Long-term cART has no significant effect on the 10-year CVD risk in HIV/AIDS patients. Higher CVD risk in HIV/AIDS patients are mainly associated with CD4 + T lymphocyte counts<200×10 6 cells/L and traditional CVD risk factors, including age≥50 years old, smoking, hypertension, diabetes and dyslipidemia.

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
Abnormalities, Multiple/genetics* ; Child ; Histone-Lysine N-Methyltransferase/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Syndrome

Objective To comparatively analyze the safety and efficacy of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke.Methods A total of 116 patients with acute anterior circulation large-artery occlusive stroke,admitted to our hospitals from October 2015 to March 2018,were chosen in our study;their clinical data were analyzed retrospectively.Among them,63 patients accepted direct mechanical thrombectomy and 53 accepted bridging therapy.The preoperative baseline data and the diagnoses and treatments of the two groups were analyzed;the degrees of modified thrombolysis in cerebral infarction (mTICI),incidences of hemorrhage transformation and symptomatic intracranial hemorrhage,and modified Rankin scale (mRS) scores and mortality rate 90 d after operation were compared between the two groups.Results The preoperative Alberta stroke program early CT scale (ASPECTS) and Glasgow Coma Scale (GCS) scores of the direct mechanical thrombectomy group were significantly lower than those of the bridge therapy group (P＜0.05),and the time from onset to admission was significantly longer than that of the bridging therapy group (P＜0.05).The incidence of postoperative hemorrhage transformation in the direct mechanical thrombectomy group was significantly higher than that in the bridging therapy group (34.9％ vs.17.0％,P＜0.05),but there were no significant differences in the effective recanalization rate (69.8％ vs.79.3％),intracranial symptomatic hemorrhage rate (15.9％ vs.7.6％),favorable outcome rate (28.6％ vs.35.9％) and mortality (22.2％ vs.17.0％) between the two groups (P＞0.05).Conclusion The clinical efficacy and safety of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke are similar.

Objective:To analyze the data of the Bethesda system for reporting thyroid cytopathology applied in a comprehensive cancer center and to evaluate the diagnostic ability of fine needle aspiration (FNA).Methods:We retrospectively reviewed the medical records of 5 729 cases applying this reporting system at Cancer Hospital, Chinese Academy of Medical Sciences. The series were from 5 011 patients including 1 174 men and 3 837 women, and their median age was 45 years (range, 7-88 years). FNA results were correlated with final histological diagnosis after surgery and the accuracy of FNA diagnosis and the malignancy rates for each of categories were also analyzed.Results:Among 5 729 thyroid aspirates, aside from 456 (8.0%) cases with nondiagnostic or unsatisfactory (ND/UNS) outcomes, 1 055 (18.4%) cases were benign, 409 (7.1%) cases showed atypical of undetermined significance or follicular lesions with undetermined significance (AUS/FLUS), 80 (1.4%) cases were follicular neoplasm or suspicious for follicular neoplasm (FN/SFN), 982 (17.1%) cases were suspicious for malignancy (SUS), and 2 747 cases were malignant (47.9%). Of 5 729 cases, 3 239 had received thyroidectomies after FNA, 95.99% of them were proven histologically to be malignant, with following malignancy rates in individual FNA categories: ND/UNS 75.00%; benign 40.91%; AUS/FLUS 77.67%; FN/SFN 41.67%; SUS 96.86%; and malignant 99.96%. FNA predicted malignancy with sensitivity, specificity, accuracy, positive predictive value and negative predictive values of 98.8%, 60.5%, 97.7%, 98.9% and 59.1%, respectively.Conclusions:The data of the Bethesda reporting system indicates high proportion of malignant diagnosis and high risk of malignancy at all FNA diagnostic categories. FNA offers high diagnostic accuracy and positive predictive value for the diagnosis of thyroid diseases.

Objective: To evaluate the utility of the BRAF^V600E mutation detection in different cytoloy categories and to determine if the VE1 antibody can serve as a screening tool for the detection of BRAF^V600E mutation in thyroid fine needle aspiration (FNA) specimens. Methods: A total of 273 FNA residual specimens were collected. BRAF^V600E testing was performed on these liquid-based specimens. And also 78 specimens with enough residual cells were stained with VE1 antibody. Comparisons of molecular and immunocytochemistry results with clinicopathological outcomes were performed. SPSS 17.0 software was used to analyze the data. Results: There were 70 indeterminated diagnoses in 273 cases with FNAs. Fifty-eight cases were proven to be papillary thyroid carcinoma (PTC) by histology, including 9 cases of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 3 cases of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), and 46 cases of suspicious for malignancy (SM). BRAF^V600E analysis detected PTC in 3 of 9 cases with AUS/FLUS, and in 31 (67.4%) of 46 cases with SM. The sensitivity of immunostaining with VE1 antibody was 62.8%(27/43) and the specificity was 91.4% (32/35). VE1 expression showed moderately concordance with the molecular mutation (κ=0.524, P<0.001). Conclusions Additional BRAF^V600E detecting can improve the diagnostic efficacy for PTC in AUS/FLUS and SM. VE1 expression may be an alternative method for BRAF^V600E detecting when molecular detecting is unavailable.

Objective: To explore the feasibility of bronchoscopic brushing liquid-based slide cytology combined with automatic immunocytochemistry (ICC) for pathological typing of lung cancer. Methods: A liquid-based thin-prep was prepared from 171 bronchoscopic brushing specimens of patients with pulmonary lesions. ICC was detected by automatic immunohistochemistry instrument while cytomorphological diagnosis was made. The results were compared with those of histopathological diagnosis. Results: Among 171 patients, 130 (76.0%) could be classified by cell morphology alone, including 31 squamous cell carcinomas, 44 adenocarcinomas and 55 small cell carcinomas; 162 (94.7%) could be classified by cell morphology combined with ICC, including 38 squamous cell carcinomas, 61 adenocarcinomas and 63 small cell carcinomas (P<0.001). According to the gold standard of histopathological diagnosis, the coincidence rate of cytomorphology combined with ICC was higher than that of cell morphology alone. The coincidence rate of squamous cell carcinoma was increased from 85.2% to 97.1% (P=0.093), adenocarcinoma from 92.5% to 98.0% (P<0.001), and small cell carcinoma from 96.1% to 98.3% (P=0.465). Conclusion The combination of liquid-based thin-prep cytology and automatic immunohistochemistry can effectively improve the accuracy of pathological typing of brushing specimens under fiberoptic bronchoscopy, and provide more objective diagnostic results for clinical treatment.

Objective To explore the feasibility of bronchoscopic brushing liquid?based slide cytology combined with automatic immunocytochemistry ( ICC ) for pathological typing of lung cancer. Methods A liquid?based thin?prep was prepared from 171 bronchoscopic brushing specimens of patients with pulmonary lesions. ICC was detected by automatic immunohistochemistry instrument while cytomorphological diagnosis was made. The results were compared with those of histopathological diagnosis. Results Among 171 patients, 130 ( 76.0%) could be classified by cell morphology alone, including 31 squamous cell carcinomas, 44 adenocarcinomas and 55 small cell carcinomas; 162 ( 94.7%) could be classified by cell morphology combined with ICC, including 38 squamous cell carcinomas, 61 adenocarcinomas and 63 small cell carcinomas ( P ＜ 0. 001 ). According to the gold standard of histopathological diagnosis, the coincidence rate of cytomorphology combined with ICC was higher than that of cell morphology alone. The coincidence rate of squamous cell carcinoma was increased from 85.2% to 97.1%(P＝0.093), adenocarcinoma from 92.5% to 98.0%(P＜0.001), and small cell carcinoma from 96.1% to 98.3%( P＝ 0.465). Conclusion The combination of liquid?based thin?prep cytology and automatic immunohistochemistry can effectively improve the accuracy of pathological typing of brushing specimens under fiberoptic bronchoscopy, and provide more objective diagnostic results for clinical treatment.