Objective:To investigate the accuracy, effectiveness and feasibility of MassARRAY genotyping assay in the diagnoses of neonatal genetic metabolic diseases.Methods:This is a retrospective study. From December 2016 to January 2020, newborns were screened by tandem mass spectrometry at the Zhejiang Newborn Screening Center, among which the data of 7 922 suspected positive cases of genetic metabolic diseases were collected. These patients were then tested for the common variants of 27 genetic metabolic diseases by MassARRAY genotyping assay, along with further testing using Sanger or next-generation sequencing used to verify and/or further search for potential variants.Results:A total of 1 408 cases were tested with MassARRAY. Among these, 307 cases were confirmed with certain genetic metabolic diseases. The detection rate of hyperphenylalaninemia was the highest, followed by primary carnitine deficiency, short acyl-coA dehydrogenase deficiency and methylmalonic acidemia. With these cases, the consistency of Sanger sequencing and MassARRAY was 100% (307/307). Another 287 cases were identified as carriers by MassARRAY with a 49.1% (141/287) consistency in reference to Sanger sequencing, mainly involving SLC22A5 and MCCC1 genes. Meanwhile, 50.8% (146/287) of these cases were found to have another variant mainly involving PAH, PTS and ACADS genes. The remaining 814 cases have no variants; 158 cases out of these patients have continuously abnormal amino acids, acyl carnitines, urine organic acid and/or other biochemical indices, and were tested by next-generation sequencing, among which 38% (60/158) were detected with two variants. In this study, a total of 513 patients with genetic metabolic disease were diagnosed, and the detection rate of MassARRAY was 59.8% (307/513). Conclusions:MassARRAY genotyping assay can be used as an early molecular screening method for neonatal genetic metabolic diseases. The detection rate is particularly high in diseases with a high concentration of hotspot variants, such as hyperphenylalaninemia and primary carnitine deficiency. The future application value of MassARRAY should be further improved by continuously optimizing its ability to identify new disease genes and potential variable sites.

BACKGROUND: Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. METHODS: A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. RESULTS: At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046). CONCLUSIONS For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Humans ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Coronary Occlusion/surgery* ; Prognosis ; Angina, Unstable/surgery* ; Chronic Disease ; Risk Factors

This paper reported a case of neonatal radial nerve palsy that was successfully treated by conservative therapy. The patient with 39 weeks of gestational age was born vaginally. On the 2nd day after birth, right wrist drop, decreased muscle strength in the right upper limb, the erythema patch, and the subcutaneous nodule on the upper arm were observed. Electromyography revealed acute denervation of the radial nerve. Based on the electromyography results combined with clinical evaluations, neonatal radial nerve palsy was diagnosed. The patient was treated with self-made simple splint fixation along with comprehensive treatment. At 15 days of age, the family members removed the splint fixation themselves (13 days of fixation). At the age of 20 days, the symptoms of right wrist drop had disappeared, and the grasp reflex and Moro reflex of both hands returned to normal. A follow-up electromyography conducted at six months after discharge showed no obvious abnormalities.

Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.

OBJECTIVE: To explore the effect of the composition ratio on substitution of sulfate group in sulfated exopolysaccharide (EPS) from and how sulfate modification affects the anti-tumor activity of EPS. METHODS: We used a chlorosulfonic acid-pyridine method to modify EPS and analyzed the effect of esterification ratio on the degree of sulfate substitution using barium chloride turbidimetry. The sulfate groups binding with EPS were analyzed with infrared spectrum analysis. CCK-8 assay was used to evaluate the inhibitory effect of EPS sulfate (SEPS) on the proliferation of human colon cancer HCT 116 cells, and annexin V-FITC/PI double staining was used to assess the pro-apoptotic effect of SEPS in the cells. RESULTS: The esterifying agent and EPS at the composition ratios of 1:1 and 2:1 resulted in sulfate substitution of 0.98% (SEPS-1) and 1.18% (SEPS-2), respectively, and the substitution was improved by increasing the ratio of the esterifying agent ( < 0.05). Infrared spectrum analysis showed that the S=O stretching vibration absorption peak of -OSO appeared near 1249 cm, indicating that the sulfate group combined with EPS to form sulfate. CCK-8 assay showed that SEPS-1 produced stronger inhibitory effects on the proliferation of HCT 116 cells than EPS within the concentration range of 0.02-0.10 mg/L ( < 0.05). At the concentrations of 0.04-0.08 mg/L, SEPS-2 showed a lower anti-tumor activity than SEPS-1 ( < 0.05). SEPS-1 also showed stronger pro-apoptotic effect than EPS, and as its concentration increased, SEPS-1 dose-dependently increased the ratio of early apoptotic cells and necrotic cells; the cells treated with 0.06, 0.08 and 0.10 mg/mL SEPS-1 showed early apoptotic rates of 6.38%, 11.8% and 12.5%, and late apoptotic and necrotic rates of 5.26%, 8.04% and 6.80%, respectively. CONCLUSIONS The composition ratio of the esterifying agent has a direct impact on the degree of substitution of EPS, which can be improved by increasing the ratio of the esterifying agent. Sulfate modification of EPS can enhance its antitumor activity, which, however, is not directly related with the degree of substitution.

Objective: To analyze the feasibility of axillary lymph node staging through sentinel lymph node biopsy (SLNB) after neoad-juvant chemotherapy (NAC) in patients with node-positive breast cancer and to explore the follow-up treatment of these patients. Methods: Clinical data of 82 patients with node-positive breast cancer before NAC in Tianjin Medical University Cancer Institute and Hospital from January 2016 to January 2018 were analyzed retrospectively. All these patients accepted SLNB after NAC. The detection rate, accuracy, false negative rate (FNR), and influencing factors were analyzed. Results: A nodal pathological complete response (PCR) was achieved in 43 of 82 patients. The PCR rate was 52.4%. The detection rate, accuracy, and FNR were 97.56% (80/82), 88.75% (71/80), and 23.08% (9/39), respectively. The accuracy of 1, 2, and≥3 SLNs detected were 90.9% (20/22), 66.7% (10/15), and 95.3% (41/43), respectively. The FNRs were 20.0% (2/10), 71.4% (5/7), and 9.1% (2/22), respectively (both P<0.05). Conclusions: Due to its overall high FNR, without clinically acceptable limits, post-NAC SLNB cannot completely replace axillary lymph node dissection (ALND) in node-positive patients. However, with no less than 3 SLNs detected, SLNB can accurately evaluate the status of axillary lymph nodes.

Objective To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow?up information of them was collected and analyzed retrospectively. Results Of the 993 patients, primary tumor located in the upper?outer quadrant ( UOQ) in 556 patients ( 56.0%), the lower?outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper?inner quadrant (UIQ) in 186 (18.7%), and the lower?inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper?inner quadrant received endocrine therapy. The estimated 5?year disease?free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P＜0.001). The 5?year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences ( P＜0.001). Multivariate analysis showed that 5?year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups ( P＜0.001), and 5?year mortality risks were increased in these three groups (P＝ 0.002). Conclusion Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.

Objective To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow?up information of them was collected and analyzed retrospectively. Results Of the 993 patients, primary tumor located in the upper?outer quadrant ( UOQ) in 556 patients ( 56.0%), the lower?outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper?inner quadrant (UIQ) in 186 (18.7%), and the lower?inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper?inner quadrant received endocrine therapy. The estimated 5?year disease?free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P＜0.001). The 5?year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences ( P＜0.001). Multivariate analysis showed that 5?year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups ( P＜0.001), and 5?year mortality risks were increased in these three groups (P＝ 0.002). Conclusion Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.

Objective: To analyze the information of patients with acute myocardial infarction (AMI) in a single center during last 6 years, and to distinguish the clinical differences of patients between TakoSTubo cardiomyopathy (TTC) and ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1042 consecutive patients with primarily diagnosed acute anterior ST-segment elevation (STEMI) admitted in our hospital from 2008-01 to 2014-04 were retrospectively enrolled. The relevant patients were studied in 2 groups:TTC group, the patients with coronary angiography (CAG) and the contrast study of left ventricle corrected TTC diagnosis, n=10, and STEMI group, the patients received CAG within 6 hours of on set with conifrmed left anterior descending singlevessel disease at the same period of time as TTC patients,n=32. The basic clinical characteristics, levels of blood lipids, MI related biomarkers, the incidence rate of pathological Q wave, QTc interval and negative T wave in 12-lead ECG were compared between 2 groups. Results: The percentage of corrected TTC diagnosis in patients with primarily diagnosed STEMI was 1.06%. The female gender in TTC group and STEMI group was 100% vs 9%,P<0.01, TTC group had more patients with stress history before on set than that in STEMI group (70% vs 22%,P=0.02), lower levels of MI related biomarkers as CK (486 ± 249) U/L vs (716 ± 132) U/L, CK-MB (13.5 ± 17.1) mg/L vs (47.5 ± 21.9) mg/L, cTnI (22.8 ± 16.3) ng/mL vs (56.4 ± 24.0) ng/mL, allP<0.01. The age of morbidity, the ratios of hypertension, diabetes mellitus and blood lipids were similar between 2 groups. The frequency of abnormal Q-wave in ECG was similar between 2 groups, while the QTc interval was different in TTC group and STEMI group (630 ± 117) ms vs (540 ± 62) ms,P=0.001, the negative T waves in ECG leads II, III, aVF, aVR and V6 were as (100.00% vs 3.13%), (60.00% vs 6.25%), (90.00% vs 3.13%), (100.00% vs 21.88%), (100.00% vs 46.88%), allP<0.05. Conclusion: TTC patients with the main presentation as ST-segment elevation are usually having emotional or physical stress before on set, with obviously prolonged QTc interval and more frequency of negative T waves in ECG.

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic