Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Medullary thyroid carcinoma(MTC)is a rare thyroid malignancy,which is more aggressive with high metastasis and recurrence rate.Surgical treatment is the preferred treatment option for MTC.Targeted therapy and immunotherapy have gradually become new treatment strategy for MTC.The pathology of MTC was updated in the 5th edition WHO classification of endocrine and neuroendocrine tumor in 2022.This review summarized the update of MTC pathology focusing on the histologic grading schemes,gene screening and genetic counseling.

Objective:To investigate the effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy.Methods:A retrospective analysis was conducted in 784 pregnant women including 111 cases of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy and 673 pregnant women with normal thyroid function as control group. All women were registered and delivered in the Department of Obstetrics of our hospital from April 2016 to April 2017. The complications and adverse outcomes of pregnancy in the two groups were analyzed.Results:Age, body weight before pregnancy, body mass index(BMI), 1 h plasma glucose and 2 h plasma glucose during oral glucose tolerance test in persistent isolated hypothyroxinemia group were higher than those in control group( P<0.05), with increased incidence of anemia during pregnancy( P<0.05). However, there were no significant differences in the incidences of gestational diabetes mellitus and gestational hypertension between the two groups( P>0.05). No significant statistical differences were found in macrosomia, stillbirth, neonatal malformation, postpartum hemorrhage, acute delivery, premature delivery, fetal intrauterine development delay, and small full-term infants between the two groups( P>0.05). Logistic regression analysis showed that age( OR=1.1, 95% CI 1.0-1.1, P=0.002) and pre-pregnancy body weight( OR=1.0, 95% CI 1.0-1.1, P=0.046) were risk factors for the occurrence of persistent isolated hypothyroxinemia in the first and second trimesters of pregnancy. Persistent isolated hypothyroxinemia in the first and second trimesters was associated with anemia during pregnancy( OR=1.9, 95% CI 1.1-3.2, P=0.024). Conclusions:Pregnant women who are older and heavier before pregnancy should pay more attention to their thyroid function. Pregnant women with persistent isolated hypothyroxinemia in the first and second trimesters should be concerned for anemia.

Objective:To Investigate comprehensive predictive ability of first-trimester complete blood count combined with maternal characteristics for gestational diabetes mellitus (GDM).Methods:From May 2015 to July 2018, 1 412 pregnant women were retrospectively screened at the Fifth People′s Hospital of Shanghai, Fudan University. We recruited 258 women who developed GDM and 1 154 women who had normal glucose level during pregnancy. At the first visit, clinical data and complete blood count result were obtained. GDM prediction models were established through logistic regression analysis of GDM related risk factors and the prediction abilities of each model were compared.Results:Logistic regression analyses identified age, pre-pregnancy body mass index, previous GDM history, family history of diabetes mellitus, the neutrophil-to-lymphocyte ratio, leukocyte, neutrophil, and monocyte counts were significantly independent predictors of GDM. In the entire cohort, the predictive ability of neutrophil and monocyte counts together with maternal basal characteristics model for the development of GDM [areas under the receiver operating characteristic curve (AUC-ROC)=0.809, integrated discrimination improvement (IDI)=0.056, P=0.001] was the best among various models (basal characteristics model, AUC-ROC=0.753; Monocyte count+ basal characteristics model, AUC-ROC=0.764; neutrophil count + basal characteristics model, AUC-ROC=0.775). Similar results obtained by the same way in all pregnant women without previous GDM history. Conclusion:It could improve the prediction of GDM with model incorporated maternal characteristics and first-trimester neutrophil and monocyte counts.

Objective:To compare and analyze the calcification characteristics and diagnostic efficiency of different breast lesion types using digtal breast tomosynthesis (DBT) and full-field digital mammography (FFDM).Methods:Totally 1 263 patients who underwent both DBT and FFDM at the same time from January 2015 to December 2018 in Dahua Hospital, Xuhui district, Shanghai were analyzed retrospectively. Benign and malignant calcification should be confirmed by pathology or a follow-up of 24 months or more using mammography, and the results of DBT and FFDM were taken as a gold standard. The detection rate and diagnostic efficiency of different types of benign and malignant breast calcification with the two methods were compared and analyzed. The detection rate of morphology and distribution of malignant calcification were compared among groups.Results:There were 240 cases with non-dense breast including 56 cases with benign calcification and 13 cases with malignant calcification. Meanwhile, there were 1 023 cases with dense breast, including 356 cases with benign calcification and 63 cases with malignant calcification. In the cases of non-dense breast, the detection rates of benign calcification by DBT and FFDM were 22.9% (55/240) and 21.7% (52/240), whereas the rates of malignant calcification were 5.0% (12/240) and 4.6% (11/240), all without statistically significances（χ2=0.108, 0.046, P>0.05). No significant differences were observed in the morphology and distribution of malignant calcification detection rates ( P>0.05). In the cases of dense breast, the benign calcification detection rates by DBT and FFDM were 34.2% (350/1 023) and 31.9% (326/1 023), whereas the detection rates of malignant calcification were 6.0% (61/1 023) and 4.9% (50/1 023), all without statistically significances (χ2=1.273 and 1.153, P>0.05). DBT detected more cases of amorphous and cluster distribution of malignant calcification than FFDM, with statistically significant differences (χ2=12.921 and 11.667, P<0.05). The area under ROC curve of DBT and FFDM in diagnosis of non-dense breast were 0.993 and 0.992, and 0.987 and 0.964 in dense breast, respectively, with no significant differences ( Z= 0.136 and 1.391, P>0.05). Conclusions:Compared with FFDM, DBT shows no statistical difference in the diagnostic efficiency of breast calcification. However, it has certain advantages in detecting malignant, amorphous, and clustered calcification in dense breast. DBT has a potential to improve the accuracy of BI-RADS classification of breast calcification.

Objective:To investigate the changes of dynamic functional connectivity between the default mode network (DMN) and executive control network (ECN) in the resting state in patients with alcohol use disorder (AUD).Methods:From September 2018 to June 2019, 23 cases of AUD group and 24 cases of healthy control (HC) group matched with age, gender, education level and handedness were collected at Renmin Hospital of Wuhan University. Mini-mental state examination (MMSE) and Michigan alcoholism screening test (MAST) were performed in all subjects for cognition and alcohol dependence score. All the subjects underwent T 1WI-3D structural imaging and resting state functional MRI (rs-fMRI) examination. Group spatial independent component analysis (ICA) was used to select the independent components of DMN and ECN. Then dynamic changes in the functional connectivity between the DMN and the DMN were obtained by sliding window approach and clustering method. Finally, the independent sample t test was used to compare the difference of general clinical data between the two groups, the linear correlation analysis was conducted in the parameter value and MMSE and MAST scores. Results:Compared with the HC group, the static functional connectivity analysis showed that the precuneus and posterior cingulate gyrus of the DMN were enhanced in the AUD group ( P=0.016, t=2.496). The DMN and ECN functional connectivity showed four different brain activity states, the proportion of state1 increased by 6.81% and state2 decreased by 6.83% in the AUD group, state3 and state4 were relatively stable. In state1, the internal functional connectivity of the DMN in the AUD group was enhanced, while the functional connectivity between DMN and ECN was mainly enhanced. In state2, the internal functional connectivity of the ECN was enhanced, and the connectivity between the DMN and ECN was mainly weakened. The mean dwell of state2 in the AUD group was negatively correlated with the MAST score ( r=-0.433, P=0.039). Conclusions:Dynamic functional connectivity patterns between DMN and ECN have been changed in patients with AUD. Dynamic functional connectivity can reveal transient changes in brain activity, which can provide certain imaging evidence for finding changes in AUD deep brain activity.

Objective To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People′s Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m2, (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m2, (6.7±1.6) mmol/L, (6.1± 1.2) mmol/L; (22±3) kg/m2, (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM ( OR=2.799, 95% CI :1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

Objective: To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods: A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People's Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results: (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m², (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m², (6.7±1.6) mmol/L, (6.1±1.2) mmol/L; (22±3) kg/m², (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM (OR=2.799, 95%CI: 1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

This paper reports a case of a male patient with diabetes for more than 20 years who came to see doctor due to weakness, poor appetite and significantly elevated blood glucose. At first, it was considered that the poor blood glucose control of diabetes was the reason, and the possibility of diabetes related complications already existed. Hospital routine examination indicated a globulin increase and immunologic examination indicated that IgM was mainly increased. Subsequent imageological diagnosis revealed a small amount of bilateral pleural effusion, and after 2 weeks of hypoglycemic treatment, the blood glucose was significantly improved, but the symptoms still existed. In combination with the patient′s laboratory examination, considering the combination of blood system diseases, the hematology department was invited for consultation. Immunoelectrophoresis, bone marrow cytology, and flow cytometry were further conducted, and the patient was diagnosed with Waldenstrom macroglobulinebia. Bortezomib + dexamethasone regimen was given for chemotherapy. Currently, the patient has received 1 course of chemotherapy, and the symptoms of poor appetite were significantly improved. Coexistence of diabetes mellitus and Waldenstrom macroglobulinebia is very rare in clinical practice, and it is easy to be misdiagnosed as a complication of diabetes mellitus, both of which can be manifested as poor appetite, weakness, peripheral neuropathy and other symptoms. When diabetic patients have abnormal immunoglobulin increases and other abnormal test results that cannot be well explained by diabetes, other potential disorders, such as hematological diseases, should be considered to avoid missed diagnosis.

Objective: To explore the clinical value of new rapid pathological diagnosis technology in the examination of cervical lesions in primary medical institution. Methods: In the Affiliated Hospital of Yangzhou University, 25 cases of cervical scraping and 22 cases of cervical biopsy were selected.Twenty-five cases of cervical scraping scraped two wipers during operation, the results were compared with conventional pathological techniques and new rapid pathological diagnosis techniques.Twenty-two cases of cervical biopsy used a new rapid pathological diagnosis technique to perform cytological diagnosis of biopsy tissue rolls in biopsy operation.According to the results of rapid pathological diagnosis, the biopsy operation plan was adjusted to analyze the clinical value of the new rapid pathological diagnosis technique in cervical lesions in primary medical institution. Results: The new rapid pathological diagnosis technology required less space and no pollution, and the diagnosis took about 2-3 min, which did not affect the normal inspection operation.Twenty-five cases of cervical scraping were produced with new rapid pathological diagnosis technique, and the quality of cervical scraping produced with conventional pathological technique was consistent, which could satisfy the needs of pathological cytological diagnosis; twenty-two cases of cervical biopsy under the vaginal device were assisted by this technology and it could increase the positive rate of the first biopsy. Conclusion Cervical scraping and cervical biopsy are still the main methods for cervical lesions examination in primary hospitals.The new rapid pathological diagnosis technology can provide the real-time pathological diagnosis of cervical scraping, improve the positive detection rate of the first biopsy of cervical biopsy, and the cost is low, suitable for promotion in primary medical institution.