1.Clinicopathological and molecular characterization of high-grade endometrial carcinoma with POLE mutation: a single center study
Shuangni YU ; Zezheng SUN ; Liju ZONG ; Jie YAN ; Mei YU ; Jie CHEN ; Zhaohui LU
Journal of Gynecologic Oncology 2022;33(3):e38-
Objective:
The molecular classification system of endometrial carcinoma (EC) in ‘The Cancer Genome Atlas’ is widely acknowledged for its prognostic utility. Subsequently, more simplified classification system that incorporate DNA polymerase epsilon (POLE) exonuclease domain mutations, mismatch repair deficiencies (MMRd), and abnormal p53 (P53abn) has also demonstrated its clinical utility. These classifications helped identifying a ‘POLE ultramutated’ (POLEmut) category of patients, most of whom show excellent prognoses despite having high-grade ECs. We aimed to investigate the clinicopathological and molecular characteristics of high-grade ECs with POLEmut.
Methods:
We investigated 414 patients with high-grade ECs (including endometrioid carcinomas grade 3, serous carcinomas, clear cell carcinomas, mixed carcinomas, undifferentiated and dedifferentiated carcinomas, and carcinosarcomas) by sequencing and immunohistochemical staining.
Results:
Forty-three tumors (10.4%) were classified as POLEmut, including 2 with new, possibly pathogenic POLE mutations at P286C and L424V. These patients had very good prognoses except for 1 with stage IV disease and residual tumor. Eleven patients in this group also had P53abn and 4 had MMRd; molecular analysis revealed that patients with synchronous POLE pathogenic mutation and other mutations had a POLEmut or MMRd phenotype; survival analysis found no difference in prognosis between these patient categories. The prognoses of patients in the POLEmut EC group were not significantly influenced by treatment or risk category.
Conclusions
Patients with high-grade EC exhibiting POLEmut have very good clinical outcomes, and should be identified urgently in daily work owing to their conflicting morphology. Our findings also provide guidance on subclassifying ECs with poor histological appearance.
2.Comparison of surgical effect of various circulatory pathways on replantation of severed distal segment of digits
Lei REN ; Kezhi HU ; Bo LYU ; Zezheng YAN ; Yanbing KANG ; Shichao ZHANG ; Zhonglai XIE ; Ming TANG ; Hui CHEN
Chinese Journal of Microsurgery 2024;47(4):430-437
Objective:To investigate the surgical effect of various circulatory pathways on replantation of severed distal segments of digits.Methods:From June 2017 to June 2023, a total of 137 patients (162 digits) who received digit replantation surgery in the Department of Trauma Orthopaedics and Microsurgery of Guilin People's Hospital were retrospectively studied. The patients were 82 males (97 digits) and 55 females (65 digits) aged 11.0 months to 51.0 years old, with 31.7 years old in average. The injured digits were 36 thumbs, 43 index fingers, 32 middle fingers, 28 ring fingers and 23 little fingers. Causes of injury: 55 digits were of electric saw, 68 of sharp object cut, 26 of twisting crush and 13 of degloving injury. According to the circulatory pathways, 66 patients (88 digits) were assigned to a physiological replantation group (PRG), 50 patients (53 digits) to an arterio-venolisation group (AVG) and 21 patients (21 digits) to a nail bed bloodletting group (NBG). Functional recovery was evaluated according to the Evaluation Standard of Severed Finger Functional of Hand Surgery of Chinese Medical Association. Analysis of variance or chi-square test was employed to analyse the age, gender, time from injury to surgery, surgery time, incidence of vascular compromise of the replanted digit, survival rate, score of functional recovery of the affected digit at 6 months after surgery, and incidence of postoperative complications in each group. P<0.05 was considered statistically significant. Results:All patients were included in the 6-10 months of postoperative follow-up, with an average of 7.2 months. Regarding the score of functional recovery of affected digit according to the Evaluation Standard of Severed Finger Functional of Hand Surgery of Chinese Medical Association, PRG (86.3 points±7.9 points) was higher than that of NBG (78.3 points±11.2 points) and AVG (70.7 points±8.6 points), with statistically significant differences ( P<0.05 for both). In terms of the incidence of vascular compromise, PRG (3 digits for 3.4%) was lower than that of NBG (1 digit for 4.8%) and AVG (6 digits for 11.3%), with statistically significant differences ( P<0.05 for both). Of the survival rate, PRG (81 digits for 92.0%) was superior to that of NBG (18 digits for 85.7%) and AVG (42 digits 79.2%), with statistically significant differences ( P<0.05 for both). While of the incidence of postoperative complications, PRG (12.6%) was lower than that of AVG (17.1%) and NBG (21.2%), with statistically significant differences ( P<0.05 for both). Conclusion:For a severed distal segment of digit, the physiological replantation is preferred. For the digit with undetectable return veins, effective replantation can be achieved by the arterio-venolisation or nail bed exsanguination.
3.Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributableto Its Key Ingredient Berberine
Xu XIZHAN ; Gao ZEZHENG ; Yang FUQUAN ; Yang YINGYING ; Chen LIANG ; Han LIN ; Zhao NA ; Xu JIAYUE ; Wang XINMIAO ; Ma YUE ; Shu LIAN ; Hu XIAOXI ; Lyu NA ; Pan YUANLONG ; Zhu BAOLI ; Zhao LINHUA ; Tong XIAOLIN ; Wang JUN
Genomics, Proteomics & Bioinformatics 2020;18(6):721-736
Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mecha-nisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with ber-berine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further stan-dardization and widespread application of TCM in many diseases.
4.MRI-based quantitative analysis of paraspinal muscle characteristics in patients with osteoporotic ver-tebral compression fractures
Zezheng CHEN ; Fangyong WANG ; Wenjie ZHANG
Chinese Journal of Spine and Spinal Cord 2024;34(6):595-601,619
Objectives:To compare and analyze the MRI characteristics and fatty infiltration(FI)of the lum-bar spine in patients with and without osteoporotic vertebral compression fracture(OVCF)to explore their rela-tionships with fracture.Methods:46 patients with OVCF(70.67±11.99 years old;11 males,35 famales)were retrospectively analyzed,and 46 age-(70.76±5.40)and sex-(11 males,35 famales)matched osteoporotic pa-tients without OVCF were taken as the control group.Paravertebral muscle FI,cross-sectional area(CSA),and vertebral bone quality(VBQ)score were measured on lumbar MRI.Independent samples t-test was used to compare the differences between the OVCF group and the control group,and regression analysis was per-formed to explore the risk factors for the development of OVCF.Results:Patients in the OVCF group had significantly higher VBQ scores(P<0.05)and significantly higher paravertebral muscle FI(P<0.05)than those in the control group.There was no significant difference in CSA of paravertebral muscles between the two groups.VBQ score(OR=1.963,P<0.01)and FI of paravertebral muscles represented by L4(OR=1.203,P<0.01)were the independent risk factors for OVCF.Conclusions:The MRI parameters of lumbar spine in patients with OVCF had greater VBQ scores and paravertebral muscle FI compared with the osteoporotic patients without OVCF;VBQ scores and paravertebral muscle FI are the independent risk factors for OVCF,and at-tentions should be paid to improve paravertebral muscle functions in the meantime of preventing OVCF.
5.Grey-scale ultrasound-based radiomics models for differentiating peripheral pulmonary adenocarcinoma and squamous cell carcinoma
Zezheng CHEN ; Lei HAO ; Lijing ZHU ; Jie ZHAO ; Xin ZHAO ; Bojuan WANG ; Jizheng TU ; Kai ZHANG ; Xinghua WANG
Chinese Journal of Medical Imaging Technology 2024;40(10):1529-1532
Objective To observe the efficacy of gray-scale ultrasound-based radiomics for differentiating peripheral pulmonary adenocarcinoma and squamous cell carcinoma.Methods Data of 88 patients with single peripheral lung adenocarcinoma and 58 patients with single peripheral lung squamous cell carcinoma proved pathologically with puncture biopsy and clearly visualized with lung ultrasound were retrospectively analyzed.The patients were divided into training set(n=103)and test set(n=43)at the ratio of 7:3.Based on gray-scale ultrasound of training set,radiomics features associated with differential diagnosis of peripheral lung adenocarcinoma and lung squamous cell carcinoma were extracted and screened.Using 4 different classifiers,including support vector machine(SVM),linear discriminant analysis(LDA),logistic regression(LR)and the least absolute shrinkage and selection operator combined with logistic regression(LASSO-LR),4 corresponding radiomics models were obtained,and the relative best models were selected according to their performances under 10-fold cross validation.The receiver operating characteristic curves were drawn,the areas under the curve(AUC)were calculated to evaluate the differentiating efficacy of each model,and DeLong test was used for the comparison.The differentiating accuracy of models were obtained under the best cutoff value with the maximum Youden index.Results The AUC of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous carcinoma in test set was 0.864,0.867,0.880 and 0.844,respectively,and no significant difference was found among 4 models(all P>0.05).Under the best cutoff value of each model,the corresponding accuracy of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous cell carcinoma was 86.05%,83.72%,88.37%and 86.05%,respectively.Conclusion Radiomics models based on gray-scale ultrasound could be used to differentiate peripheral lung adenocarcinoma and lung squamous cell carcinoma.