Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective: To evaluate the effect of ultrasound diagnosis of thyroid micro-malignant nodules and accumulate practical experience for the management of active surveillance for them, so as to avoid overtreatment. Methods: A total of 949 patients who were diagnosed with thyroid malignant nodules using ultrasonography, with the nodules being less than 1 cm in size and without regional lymph node metastasis or distant metastasis, were included. They were treated by the same surgeon of the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to December 2020. 112 patients chose immediate surgery. The rest patients were asked to accept ultrasound examination every 6 months to 1 year. Follow-up endpoints: tumor size growth of 3 mm, tumor volume increase greater than 50%, lymph node metastasis or distant metastasis. Results: The median follow-up time was 19 months. 713 patients underwent surveillance for more than 6 months. Of the 713 patients, 570 (79.9%) were women, with mean age at 43.5 years old. Tumor progression was observed in 47 (6.6%) patients with a cumulative incidence of 2.7% (1 year), 7.2% (2 years) and 9.5% (3 years). In multivariate analysis, patient age [HR=0.508, 95%CI: 0.275-0.939, P=0.031], lesion number [HR=2.945, 95%CI: 1.593-5.444, P=0.001] and tumor size [HR=2.245, 95%CI: 1.202-4.192, P=0.011] at the beginning of observation were independent risk factors for tumor progression in patients with minimal thyroid malignant nodules during follow-up. During a median (range) active surveillance of 19 (6-80) months, 74 patients chose surgery during the surveillance. Among the 186 patients who underwent surgery, only 3 patients were diagnosed with fibrotic nodules in pathology, while the rest were papillary thyroid carcinoma. The ultrasound accuracy reached 98.4%(183/186). Conclusions: Ultrasonography is an effective method of diagnosing malignant thyroid nodules. Thyroid micro-malignant nodules progress slowly. As a result, it is safe to observe them instead of taking immediate surgery. Patient age, lesion number and tumor size at the beginning of observation are independent risk factors for the tumor progression of malignant nodules.
Humans ; Female ; Adult ; Male ; Thyroid Nodule/surgery* ; Carcinoma, Papillary/surgery* ; Lymphatic Metastasis ; Thyroid Neoplasms/surgery* ; Thyroidectomy/methods* ; Watchful Waiting ; Ultrasonography ; Retrospective Studies

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO RESULTS: There was no significant difference in TcPCO CONCLUSIONS Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.
Blood Gas Monitoring, Transcutaneous ; Carbon Dioxide ; Electrodes ; Humans ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Oxygen ; Partial Pressure ; Temperature

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

The aim of this study was to identify the anti-inflammatory markers of Zhachong shisanwei pills (ZC-13) and characterize their mechanisms. UPLC/Q-TOF-MS combined with an NF-κB dual fluorescence reporter gene system and NO content detection were utilized to identify the anti-inflammatory bioactive substances in ZC-13. Network pharmacology and bioinformatics methods were used to predict the main targets and pathways of these anti-inflammatory markers, and to verify the main anti-inflammatory pathways of costunolide. Results showed that in ZC-13, four kinds of markers related to NF-κB inhibition were identified: gallic acid, ellagic acid, liquiritin apioside, glycyrrhizic acid, and four kinds of markers related to NO release inhibition were found: gallic acid, liquiritigenin, costunolide, and dehydrocostus lactone. The above components exert anti-inflammatory activities mainly through the regulation of PDK1 (3-phosphoinositide-dependent protein kinase 1), MAPK14 (mitogen-activated protein kinase), GSK3β (glycogen synthase kinase-3β) and other anti-inflammatory-related targets, and further adjust the PI3K-AKT (phosphoinositide 3-kinase- protein kinase B), MAPK, mTOR (mammalian target of rapamycin) pathways. Among them, costunolide can inhibit AKT phosphorylation and NF-κB nuclear transfer. The above results identified the anti-inflammatory markers and possible mechanisms of ZC-13, and provide a theoretical basis for standardizing the clinical application and quality of ZC-13.

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.
Aging ; Awards and Prizes ; Delivery of Health Care ; Education ; Financing, Organized ; Humans ; Mentors ; Osteoporosis ; Practice Guidelines as Topic ; Taiwan

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

To clarify the functions and mechanism of stimulated by retinoic acid gene 8 (Stra8) in spermatogenesis, we analyzed the testes from Stra8 knockout and wild-type mice during the first wave of spermatogenesis. Comparisons showed no significant differences in morphology and number of germ cells at 11 days postpartum, while 21 differentially expressed genes (DEGs) associated with spermatogenesis were identified. We speculate that Stra8 performs many functions in different phases of spermatogenesis, such as establishment of spermatogonial stem cells, spermatogonial proliferation and self-renewal, spermatogonial differentiation and meiosis, through direct or indirect regulation of these DEGs. We therefore established a preliminary regulatory network of Stra8 during spermatogenesis. These results will provide a theoretical basis for further research on the mechanism underlying the role of Stra8 in spermatogenesis.
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Cell Proliferation/genetics* ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Male ; Mice ; Mice, Knockout ; Spermatogenesis/genetics* ; Spermatogonia/metabolism* ; Testis/metabolism*

OBJECTIVETo explore the clinical effects of VSD combined with continual irrigation in treating the infection of limbs fracture after internal fixation.

METHODSFrom March 2010 to June 2015, 10 patients with infection of limbs fracture after internal fixation were treated with VSD combined with continual irrigation. There were 7 males and 3 females, aged from 11 to 58 years with an average of 34.4 years. Course of disease was from 1 to 8 months with an average of 4.8 months. Postoperative infection occurred in fractures of ulna and radius of 4 cases, tibiofibular fractures of 3 cases, calcaneal fractures of 2 cases, femoral fractures of 1 case. Eight infections were open fracture and 2 infections were close fracture. In additon to above treatment, antibiotics, dressing changing or skingrafting were used in the patients. Informations of wound surface healing, change dressings, original infection focus were observed.

RESULTSAll infections got control, the wound healing after change dressings or skingrafting, and no complications such as osteomyelitis were found. The mean treatment time was 38.4 days(ranged, 29 to 45 days) and replacement times was 2.2 times(ranged, 1 to 4 times). All patients were followed up, no recurrent infections were found at 1 year after fracture healing.

CONCLUSIONSVSD combined with continual irrigation can effectively decrease the incidence of complications and promote the wound growth, healing and considerably shorten the healing time. It is an effective method for the treatment of infection of limbs fracture after internal fixation.

Spermiogenesis is a complex process of differentiation and morphologic alteration, in which sperm acrosome formation is an important stage. Acrosome is an essential component of the sperm head, which develops in four distinct phases: Golgi, cap, acro- somal, and maturation, each supported by precise and orderly regulation of various genes. The regulatory genes which act on Golgi ap- paratus include GOPC, Hrb, SPATA16, PICK1, and CK2α', those involved in the cap phase are Fads2, syntaxin 2, Kdm3a, and UBR7, and participating in acrosomal and maturation phases are KIFC1, Rnf19a, and DPY19L2. The abnormalities of these genes may affect male fertility by influencing the connection of the nuclear dense lamina and acroplaxome with the nuclear membrane and then the fusion and transportation of vesicles. This review focuses on the genes involved in different phases of acrosome formation.
Acrosome ; physiology ; Animals ; Golgi Apparatus ; Male ; Mice ; Sperm Head ; physiology ; Spermatids ; growth & development ; Spermatogenesis ; genetics ; Spermatozoa ; growth & development