Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

OBJECTIVE: To investigate the changes in percentage of GATA3⁺ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models. METHODS: The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3⁺ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3⁺ Treg cells and the expressions of Th2 cytokines. RESULTS: Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3⁺ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3⁺ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05). CONCLUSION The percentage of GATA3⁺ Treg cells is decreased in AR patients and mouse models. GATA3⁺ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3⁺ Treg cells as a new therapeutic target for AR.
Animals ; Mice ; Cytokines/metabolism* ; Disease Models, Animal ; GATA3 Transcription Factor ; Inflammation ; Leukocytes, Mononuclear/metabolism* ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nasal Mucosa/metabolism* ; Ovalbumin ; Rhinitis, Allergic/therapy* ; T-Lymphocytes, Regulatory ; Th2 Cells/metabolism* ; Humans

Humans ; Leg/pathology* ; Skin Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*

Objective:To determine the expression of silent information regulator 1 (Sirt1) , Sirt3 and hypoxia-inducible factor 1α (HIF-1α) in cutaneous squamous cell carcinoma (CSCC) tissues and cells, and to explore their role in the occurrence and development of CSCC.Methods:From January 2019 to December 2020, 30 lesional skin tissues were obtained from patients with histopathologically confirmed poorly-, moderately- or well-differentiated CSCC, and 30 normal skin tissues were obtained from patients with non-cancerous diseases in Department of Dermatology, General Hospital of Ningxia Medical University. A CSCC cell line A431 and a human keratinocyte cell line HaCaT were cultured. Immunohistochemical study, Western blot analysis and real-time quantitative PCR (RT-PCR) were performed to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in CSCC tissues of different grades of differentiation and normal skin tissues, cytochemical and immunofluorescence staining and RT-PCR were conducted to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in A431 and HaCaT cells, respectively. Comparisons of measurement data among multiple groups were performed by using one-way analysis of variance, and comparisons between two groups by using t test. Results:Immunohistochemical study showed that the expression level of Sirt3 (expressed as the average optical density) was 100 ± 12.12, 117.72 ± 26.23, 127.32 ± 24.45, 132.71 ± 31.61 in the normal skin tissues and well-, moderately- and poorly-differentiated CSCC tissues respectively, and there was a significant difference among these groups ( F = 20.14, P < 0.001) ; the expression of Sirt1 and HIF-1α increased in turn from the normal skin tissues to the well-, moderately- and poorly-differentiated CSCC tissues, and significantly differred in these groups ( F = 174.50, 225.00, respectively, both P < 0.001) . As Western blot analysis revealed, the expression level of Sirt3 significantly differed among the normal skin tissues, well-, moderately- and poorly-differentiated CSCC tissues (expressed as relative gray value: 1.000 ± 0.132, 1.403 ± 0.411, 1.387 ± 0.393, 1.677 ± 0.683, respectively; F = 34.97, P < 0.001) , and so did the expression levels of Sirt1 and HIF-1α ( F = 69.29, 199.90, respectively, both P < 0.00l) , with a gradually increasing trend in their expression levels from the the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues. RT-PCR showed that the mRNA expression of Sirt3, Sirt1 and HIF-1α was sequentially increased from the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues, and significant differences were observed among these groups ( F = 113.00, 174.50, 50.33, respectively, all P < 0.001) . The protein expression levels of Sirt3, Sirt1 and HIF-1α were significantly higher in the A431 cells than in the HaCaT cells ( t = 16.75, 18.34, 27.76, respectively, all P < 0.001) , and so were their mRNA expression levels ( t= 14.22, 9.62, 16.86, respectively, all P < 0.001) . Conclusion:Increased expression of Sirt3, Sirt1 and HIF-1α was observed in CSCC tissues and cells, which may promote the occurrence and development of CSCC.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.