[Methylthioadenosine phosphorylase and p16 as surrogate diagnostic markers for CDKN2A homozygous deletion in brain tumors].

Objective: To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. Methods: A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined. Results: Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion (P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions: MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

[Deep learning-based dose prediction in radiotherapy planning for head and neck cancer].

OBJECTIVE: To propose an deep learning-based algorithm for automatic prediction of dose distribution in radiotherapy planning for head and neck cancer. METHODS: We propose a novel beam dose decomposition learning (BDDL) method designed on a cascade network. The delivery matter of beam through the planning target volume (PTV) was fitted with the pre-defined beam angles, which served as an input to the convolution neural network (CNN). The output of the network was decomposed into multiple sub-fractions of dose distribution along the beam directions to carry out a complex task by performing multiple simpler sub-tasks, thus allowing the model more focused on extracting the local features. The subfractions of dose distribution map were merged into a distribution map using the proposed multi-voting mechanism. We also introduced dose distribution features of the regions-of-interest (ROIs) and boundary map as the loss function during the training phase to serve as constraining factors of the network when extracting features of the ROIs and areas of dose boundary. Public datasets of radiotherapy planning for head and neck cancer were used for obtaining the accuracy of dose distribution of the BDDL method and for implementing the ablation study of the proposed method. RESULTS: The BDDL method achieved a Dose score of 2.166 and a DVH score of 1.178 (P < 0.05), demonstrating its superior prediction accuracy to that of current state-ofthe-art (SOTA) methods. Compared with the C3D method, which was in the first place in OpenKBP-2020 Challenge, the BDDL method improved the Dose score and DVH score by 26.3% and 30%, respectively. The results of the ablation study also demonstrated the effectiveness of each key component of the BDDL method. CONCLUSION: The BDDL method utilizes the prior knowledge of the delivery matter of beam and dose distribution in the ROIs to establish a dose prediction model. Compared with the existing methods, the proposed method is interpretable and reliable and can be potentially applied in clinical radiotherapy.

Therapeutic effects and safety of apatinib mesylate on patients with gastric carcinoma peritoneal metastasis in SOX scheme.

OBJECTIVE: The aim of this study was to investigate the diagnostic values of serum tumor markers in gastric carcinoma peritoneal metastasis and the therapeutic efficacy as well as safety of apatinib mesylate combined with Geo+Oxaliplatin (SOX) scheme treatment in gastric carcinoma peritoneal metastasis. PATIENTS AND METHODS: Sixty patients with gastric carcinoma peritoneal metastasis and 11 patients without gastric carcinoma peritoneal metastasis were selected as the research subjects. The levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9] and abdominal irrigating solution exosome [micro ribonucleic acid (miR)-21 and miR-320c] and the differences in their diagnostic values were compared and analyzed. The patients with gastric cancer peritoneal metastases are then divided into two groups, one for control (30 cases receiving just SOX scheme treatment) and the other for the experiment (30 cases receiving SOX scheme treatment plus apatinib mesylate). Besides, the differences in serum tumor marker level, therapeutic efficacy, overall survival (OS), complication rating, and Quality of Life Questionnaire-Core-30 (QLQ-C30) score among patients after treatment were compared. RESULTS: Demonstrated that serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9 levels of patients in the transfer group were remarkably enhanced compared with those of patients in the non-transfer group, and the levels of abdominal irrigating solution exosome (miR-21 and miR-320c) were reduced compared with those in non-transfer group (p<0.05). The area under the curve (AUC) of the diagnosis of gastric carcinoma peritoneal metastasis by each index were 0.553, 0.880, 0.832, 0.619, 0.863, 0.651, 0.918, and 0.903, respectively. Patients in the experimental group's serum levels of CEA, CA125, CA211, CA242, CA724, and CA19-9 were noticeably lower after therapy compared to those in the control group, and their median OS was also noticeably longer (p<0.05). After treatment, the objective remission rate (ORR) and disease control rate (DCR) of the control group and experimental group amounted to 6.7% vs. 30.0% and 50.0% vs. 86.7%, respectively. ORR and DCR of the experimental group were notably higher (p<0.05). Between the patients in the control group and the experimental group, there were no glaring variations in the frequency of problems (hypertension, nausea, vomiting, bone marrow suppression, hand-foot syndrome, and leucopenia) (p>0.05). The cognitive function, emotional function, and life health scores of patients in the experimental group were significantly higher than those in the control group (p<0.05), which suggested that serum tumor markers and miR-21 as well as miR-320c showed high diagnostic efficiency in gastric carcinoma peritoneal metastasis. CONCLUSIONS: Apatinib mesylate combined with SOX scheme treatment was more effective in treating gastric carcinoma peritoneal metastasis and possessed the same safety as single SOX scheme treatment. Hence, it is worthy of clinical promotion.

[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

[Pay attention to molecular pathological diagnosis of pediatric glioma].

Glioma is one of the most common central nervous system tumors in children.Increasing studies show that compared with adults, some gliomas in children have unique molecular genetic characteristics and completely different biological behaviors, although they are similar to adults in morphology and nomenclature. Therefore, pediatric glioma is by no means a "miniature version" of adults. In the 5th edition of WHO classification of central nervous system tumors published in the end of 2021, one of the most important revisions is the division of the classification into adult-type and pediatric-type diffuse gliomas, and the latter is further divided into pediatric-type diffuse low-grade gliomas and pediatric-type diffuse high-grade gliomas. In addition to histological morphology and clinical features, the basis of classification includes more molecular features. Therefore, in clinical practice, we need to pay more attention to the significance of molecular pathological diagnosis in the diagnosis and treatment of gliomas in children.

Site-specific therapy in cancers of unknown primary site: a systematic review and meta-analysis.

BACKGROUND: Cancer of unknown primary site (CUP) is a term applied to characterize pathologically confirmed metastatic cancer with unknown primary tumor origin. It remains uncertain whether patients with CUP benefit from site-specific therapy guided by molecular profiling. PATIENTS AND METHODS: A systematic search in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov, and of conference abstracts from January 1976 to January 2021 was performed to identify studies investigating the efficacy of site-specific therapy on patients with CUP. The quality of included studies was evaluated using the Cochrane risk of bias tool and Newcastle-Ottawa scale. Eligible studies were weighted and pooled for meta-analysis. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were assessed to compare the efficacy of site-specific therapy with empiric therapy in patients with CUP. In addition, subgroup analyses were conducted. RESULTS: Five studies comprising 1114 patients were identified, of which 454 patients received site-specific therapy, and 660 patients received empiric therapy. Our meta-analysis revealed that site-specific therapy was not significantly associated with improved PFS [HR 0.93, 95% confidence interval (CI) 0.74-1.17, P = 0.534] and OS (HR 0.75, 95% CI 0.55-1.03, P = 0.069), compared with empiric therapy. However, during subgroup analysis significantly improved OS was associated with site-specific therapy in the high-accuracy predictive assay subgroup (HR 0.46, 95% CI 0.26-0.81, P = 0.008) compared with the low accuracy predictive assay subgroup (HR 0.93, 95% CI 0.75-1.15, P = 0.509). Furthermore, compared with patients with less responsive tumor types, more survival benefit from site-specific therapy was found in patients with more responsive tumors (HR 0.67, 95% CI 0.46-0.97, P = 0.037). CONCLUSIONS: Our results suggest that site-specific therapy is not significantly associated with improved survival outcomes; however, it might benefit patients with CUP with responsive tumor types.

[Advancement in endovascular therapy of aortoiliac occlusive disease].

Aortoiliac occlusive disease (AIOD) refers to the stenosis and occlusion of the distal abdominal aorta and(or) bifurcation of the aortoiliac artery,which is mainly caused by atherosclerosis,leading to pelvic and lower limb ischemia.Open surgery has always been the main treatment for complex AIOD.However,in recent years,with the development of endovascular surgery technologies and medical instruments,its treatment concept has been greatly changed.More and more clinical evidence has proved that the long-term efficacy of endovascular therapy is not inferior to that of traditional open surgery,so minimally invasive endovascular therapy has become the preferred treatment for AIOD.

[Distribution and metabolism of toxicants in rats with phenol burn].

Objective: To study the distribution and metabolism of toxicants in rats after phenol burn. Methods: In February 2019, SPF-grade healthy SD male rats were transdermally exposed to 6 mg/kg phenol to create a 5% body surface burn model of rats. High performance liquid chromatography was used to determine phenol content in rat plasma and kidney tissues after 0.25, 0.75, 2, 4, 8, 16, and 32 h, respectively. The kinetic parameters of phenol were calculated by DAS 2.0 software, and the kidney targeting of phenol was evaluated. Results: The area under the blood concentration-time curve at 0-8 h (AUC(0-8)) of the rat after phenol burn was (28.741±6.485) µg/ml·h, and the area under the blood concentration-time curve from 0 to infinite time (AUC(0-∞)) was (30.354±6.424) µg/ml·h, half-life (t(1/2)) was (2.111±0.632) h, peak concentration (C(max)) was (16.287±4.870) µg/ml, mean residence time (MRT) was (1.854±0.148) h. The target efficiency (DTE) of rat kidney was 2.91. Conclusion: Phenol burn rats have fast percutaneous absorption, rapid elimination of phenol, and have high clearance rate, short MRT, and weak substance accumulation. Phenol has relatively obvious selectivity to the kidneys.

[Clinicopathological features and molecular characteristics of tall cell and hobnail variants of papillary thyroid carcinoma].

Objective: To investigate the clinicopathological and molecular genetic characteristics of tall cell variant and hobnail variant of papillary thyroid carcinoma (PTC). Methods: Twenty-one cases of tall cell variant (TCV-PTC) of PTC (TCV-PTC) and ten cases of hobnail variant of PTC (HV-PTC), as the highly aggressive group, were collected from Xuanwu Hospital from August 2009 to August 2015. Twenty-two cases of follicular variant and 21 classical PTC cases were included as control. Relevant clinical and pathologic data were obtained, and in some cases, paraffin samples were selected for gene mutation spectrum analysis using second generation sequencing. Results: There were 18 males and 56 females; 57 patients were younger than 55 years of age, and 17 patients were 55 years or older. The mean tumor size was 1.6 cm for the high-aggressive group (TCV-PTC and HV-PTC), 1.1 cm for the follicular subtype, and 1.6 cm for the classical type. There were 54 cases with thyroid capsule invasion, 24 cases with extra-thyroidal invasion, and 45 patients with lymph node metastases. Regional recurrence occurred in 7 cases, no recurrence in 54 cases, and 13 patients were lost to follow-up. The highly aggressive group was more likely to show extra-thyroidal invasion, lymph node metastases and recurrence than those with classical PTC (P<0.05). Within this cohort, BRAF V600E mutation was detected in 53 cases and TERT promoter mutation in 6 cases. Compared with the single mutation group and no mutation group, BRAF and TERT promoter co-mutation group was more commonly detected in older age, male, larger tumor size and more prone to extra-thyroid invasion (P<0.05). In addition, among BRAF and TERT co-mutation cases, the highly-aggressive group accounted for the highest proportion (5/6). Conclusions: TCV-PTC and HV-PTC, as highly-aggressive variants of PTC, show more aggressive biologic behavior (more lymph node metastasis, external thyroid invasion and recurrences) than the classical and follicular variants of PTC. Coexisting BRAF and TERT promoter mutations may be associated with invasive biologic behavior.

[Drug-coated balloons versus bare metal stent for treatment of femoropopliteal lesions:36 month follow-up results of single center].

Objective: To examine the therapeutic effects of drug-coated balloon (DCB) and bare metal stent (BMS) on primary femoropopliteal disease (FPAD) in the real world. Methods: This was a retrospective analysis of single-center follow-up results at 12,24,and 36 months of patients with FPAD lesions that were treated with DCB and BMS at Department of Aortic and Vascular Surgery, Fu Wai Hospital.One-to-one propensity score matching(PSM) was performed to balance the covariance between DCB group (137 cases) and BMS group (100 cases). Freedom from clinically driven target lesion reintervention rate(fCD-TLR) was determined by Kaplan-Meier curve.Log-rank test was used to compare the rates of fCD-TLR between DCB and BMS groups at 12,24,36 months post-operation. Results: After PSM, there were both 71 patients in each group,aged (68.0±9.6) years(range: 46 to 90 years) and (68.8±7.3) years(range: 48 to 87 years),lesion lengths were (119.6±14.2)mm(range:40 to 380 mm) and (110.8±13.1)mm(range:40 to 400 mm). The median follow-up period were 24.3 months (range:5.8 to 55.1 months).There was no death,amputation or reintervention within the 30 days after operation.The rates of fCD-TLR for DCB group at 12,24 and 36 months were 97.2%,85.9%,69.1%, and 95.8%,83.1%,59.2% for BMS group.There was no statistical difference between the two groups by Log-rank test (P=0.551). Conclusion: DCB and BMS can both maintain favorable clinical effects in FPAD patients at 12,24,36 months post-operation.

[Extraskeletal mesenchymal chondrosarcoma in central nerve system: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

[Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas].

Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case (P>0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations (P>0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.

[Chordoid glioma: a clinicopathological study].

Objective: To analyze the clinicopathological features of chordoid glioma. Methods: A total of 12 cases of chordoid gliomas from 2009 to 2020 in Xuanwu Hospital of Capital Medical University and General Hospital of Chinese People's Liberation Army were retrospectively analyzed. The clinical and imaging characteristics, pathologic and molecular characteristics were analyzed, and the relevant literature was reviewed. Results: All 12 patients (4 males and 8 females) aged from 25 to 67 years (mean 39 years) and mainly had a history of headache or/and vision loss. MRI showed that the lesions located in the third ventricle, and they showed abnormal enhancement. Pathologically, these 12 cases displayed the morphologic characteristics of chordoid gliomas, including papillary structures in two cases. Immunohistochemically, GFAP and vimentin were expressed in all 12 cases (12/12). TTF1 was also expressed in all cases (10/10). CD34 and CKpan were seen in 11 cases (11/12). EMA with dot-and/or-ring like positivity was seen in 9 cases (9/10). Tissues were available in nine chordoid gliomas for Sanger sequencing to detect PRKCA and IDH gene mutation, and eight cases (8/9) showed PRKCA gene D463H mutation. None of these cases showed IDH1 R132 and IDH2 R172 mutation. All 12 patients underwent surgery, and four were lost to follow up. The remaining eight patients were progression or recurrence free at last follow-up in January 2021. Conclusions: Chordoid gliomas have relatively distinguishing clinical and histopathological features. PRKCA gene mutation in chordoid gliomas can be considered as a biomarker for the diagnosis and differential diagnosis of chordoid gliomas, and may provide a direction for future targeted therapy.

[Clinicopathological features of diffuse leptomeningeal glioneuronal tumor].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). Methods: Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed. Results: The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients. Conclusions: DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

[Effects of protein disulfide isomerase on hyperglycemia and hypoxia/reoxygenation injury in H9c2 cardiomyocytes].

Objective: To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease. Methods: We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected. Results: PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) µmol/L、(10.0±1.0) µmol/L、(11.7±1.0) µmol/L vs (4.2±1.8) µmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) µg/L、(1.64±0.27) µg/L、(1.20±0.14) µg/L vs (2.62±0.12) µg/L, all P<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(all P<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) µg/L vs (3.03±0.10) µg/L、(2.06±0.05) µg/L vs (2.31±0.06) µg/L、(1.83±0.07) µg/L vs (1.96±0.11) µg/L、(1.20±0.06) µg/L vs (1.39±0.09) µg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) µg/L vs (0.59±0.09) µg/L、(0.62±0.04) µg/L vs (0.53±0.05) µg/L、(0.55±0.14) µg/L vs (0.51±0.12) µg/L、(0.48±0.12) µg/L vs (0.35±0.08) µg/L] in response to different treatments in cultured H9c2 cardiomyocytes (all P<0.05). Conclusion: PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.

Racial disparity in orbital morphology and spatial relations in unoperated Crouzon patients.

The altered orbital morphology of patients with Crouzon syndrome could have an impact on the planning of treatment in diverse populations, in spite of the confounding influences of different cranial suture synostosis. This study attempted to explore the differences in orbital characteristics between Asian, Caucasian patients with Crouzon syndrome, associated pansynostosis. Eighty-six preoperative computed tomograms (CT) were included (Asian Crouzon syndrome: n=10; Asian controls: n=24; Caucasian Crouzon syndrome: n=19; Caucasian controls: n=33) and measured using Mimics software (Materialise). Unique cephalometric measurements related to orbital morphology and position were designed. Crouzon syndrome and race both have interactive effects on protrusion of the globe (p=0.009) and medial horizontal angle (p=0.012) in the assessment of orbital morphology. They also interact in the width of the ethmoid sinus (p=0.009) and influence bilateral orbital relations. The anteroposterior orbital roof in Caucasian patients with Crouzon syndrome was shortened by 4.09mm (p=0.002) compared with Caucasian controls. However, in Asian patients this dimension developed normally. The anteroposterior orbital floor was significantly reduced to a similar extent in both Asian and Caucasian Crouzon patients (both p<0.001). The visual axes in Caucasian patients with Crouzon showed more inferior rotation, by 4.38° (p=0.031) than they did in Caucasian controls, but did not achieve a statistically significant difference in other comparisons. The effect of Crouzon syndrome on orbital malformation and placement is influenced by race, especially structures related to the ethmoid sinus. Asian patients need greater infraorbital advancement for better correction of orbital proptosis and aesthetic benefits, but may require less fronto-orbital advancement than Caucasian patients.

[High-grade gliomas with H3 G34R mutation: a clinicopathological study].

Objective: To analyze the clinicopathological features and probable mechanisms of high-grade gliomas with H3 G34R mutation. Methods: Five cases of high-grade gliomas with H3 G34R mutation were collected at Xuanwu Hospital, Capital Medical University, Beijing, China, from 2016 to 2019. The clinical and pathological data for each case was retrospectively reviewed. Results: The 5 patients (2 males and 3 females) aged from 15 to 45 years (mean 23 years), and had a history of headache or motor weakness. Four of them were younger than 20 years of age. Magnetic resonance imaging showed that the lesions of 3 cases were seen separately in frontal lobe, parietal lobe or temporal lobe, 1 case involved both frontal lobe and parietal lobe, and otherwise multiple lobes were involved in 1 case. Contrast enhancement could be observed in 2 cases. Pathological examination showed that glioblastoma was the most common entity, with or without primitive neuronal component. All 5 cases showed that H3 G34R was diffusely positive in tumor nuclei with ATRX loss. Moreover, p53 was overexpressed in 4 cases. None of them showed Olig2 expression. Two patients showed disease progression after surgery at 18 months and 24 months, respectively. The latter of the two deceased 3 months after tumor progression. Conclusions: The clinicopathological and molecular genetics features of high-grade gliomas with H3 G34R mutation have relatively similar clinicopathological and genetic features, and more commonly seen in young adults (vs. older adults). Thus, these tumors may be discussed further as a distinct tumor entity.