Short-term efficacy of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective:To investigate the clinical effect and safety of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 24 patients with stage Ⅲ-IV A NPC were recruited prospectively to receive two cycles of camrelizumab combined with induction chemotherapy (docetaxel 75 mg/m 2+ cisplatin 25 mg/m 2 for three consecutive days) followed by concurrent chemoradiotherapy (prescription doses: 6 996 cGy in 33 fractions for PGTV and PGTV nd, 6 006 cGy in 33 fractions for PTV 1, 5 096 cGy in 28 fractions for PTV 2, and concurrent cisplatin chemotherapy with a dose of 75 mg/m 2). The short-term efficacy and adverse reactions were evaluated. Results:After induction therapy, nasopharyngeal lesions showed an objective response rate (ORR) of 91.6%, including 45.8% of complete response (CR) and 45.8% of partial response (PR); cervical lymph nodes showed an ORR of 95.8% (CR: 4.2%; PR: 91.6%). Seventeen patients accepted a reexamination under a nasopharyngoscope, and the biting biopsy result indicated that 13 patients among them had complete pathologic response. After concurrent chemoradiotherapy, nasopharyngeal lesions and cervical lymph nodes showed CR rates of 83.3% and 91.7% and PR rates of 16.7% and 8.3%, respectively. After the induction therapy, 13 patients with stage IV A NPC had ORR (PR) rates of 92.4% and 92.4%, respectively, at nasopharyngeal lesions and cervical lymph nodes. After concurrent chemoradiotherapy, the patients with stage IV A NPC had CR rates of 84.6% and 92.3% and PR rates of 15.4% and 7.7%, respectively, at nasopharyngeal lesions and cervical lymph nodes. Major adverse reactions include leukopenia, granulopenia, anemia, radioactive acute oropharyngeal mucositis and dermatitis, digestive tract reaction, fatigue, hypothyroidism, aminotransferase elevation, and reactive capillary hyperplasia. Conclusions:Camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy can achieve high short-term efficacy for patients with locally advanced nasopharyngeal carcinoma, without increasing the incidence of adverse reactions. Its long-term efficacy deserves further research.

Analysis of Related Factors Affecting the Risk Assessment of Death during Hospitalization of Extremely Low Birth Weight Infants / 中山大学学报(医学科学版)

ObjectiveTo explore the influencing factors of different scores on predicting death risk of extremely low birth weight infants （ELBWI）. MethodsA total of 186 cases of ELBWI admitted by the Children's Hospital affiliated to Nanjing Medical University and the Lishui Branch of the Affiliated Zhongda Hospital of Southeast University were admitted from January 1， 2019 to January 1， 2021， and 125 ELBWIs were finally included after screening by inclusion and exclusion criteria. There were 47 cases in the death group and 78 cases in the survival group. General data and the items of score for neonatal acute physiology version Ⅱ （SNAP-Ⅱ）， simplified version of the score for neonatal acute physiology perinatal extension （SNAPPE-Ⅱ）， clinical risk index for babies （CRIB）， clinical risk index for babies Ⅱ （CRIB-Ⅱ） and the national critical illness score （NCIS） were collected. Univariate and multivariate analysis was performed and nomogram was evaluated using receiver operating characteristic curve （ROC）. ResultsIt was found that systolic blood pressure， maximum inhaled oxygen concentration， BE value and birth weight were important factors in ELBWI mortality risk assessment ［systolic blood pressure OR： 0.968， 95%CI： 0.938-0.999， P=0.043； maximum inhaled oxygen concentration OR： 1.020， 95%CI： 1.006-1.034， P=0.006； BE OR： 0.868， 95%CI： 0.786-0.959， P=0.005； birth weight OR： 0.994， 95%CI： 0.991-0.997， P=0.000］. ROC showed that the area under the curve of the above four variables is 0.71， and the 95% confidence interval is 0.610-0.799， which is better than CRIB score. ConclusionLower systolic blood pressure， higher inhaled oxygen concentration， higher BE and lower birthweight are important influencing factors to predict the death risk of ELBWI. The above four items should be included in the newly developed score assessment to obtain a more effective ELBWI prediction system.

Tooth number abnormality: from bench to bedside / 国际口腔科学杂志·英文版

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.

Analysis of work stress and its influencing factors among nursing staff in Tianjin City / 中华劳动卫生职业病杂志

Objective: To explore the current situation of work stress among nursing staff in Tianjin City and analyze its influencing factors. Methods: From August to October 2020, 26002 nursing staff from tertiary hospitals, secondary public hospitals, secondary private hospitals, primary hospitals, and other medical institutions in Tianjin City were selected as objects, and their general situation and working stress situation were surveyed by the general information questionnaire and the Nurse's Work Stressor Scale. Single factor analysis and multiple linear regression analysis were used to explore the influencing factors of work stress among nursing staff. Results: The average age of 26002 nursing staff was (33.86±8.28) years old, and the average working years were (11.84±9.12) years. There were 24874 women (95.66%) and 1128 men (4.34%). The total score of work stress was (79.82±21.69), and the average score of workload and time allocation dimension was the highest (2.55±0.79). The results of multiple linear regression analysis showed that marital status (β=-0.015, P=0.014), employment form as contract system (β=0.022, P=0.001), post as clinical nursing (β=0.048, P<0.001), education level (β=0.024, P<0.001), age (β=0.050, P<0.001), working years (β=0.075, P<0.001), and professional title (β=0.036, P<0.001) were the influencing factors of work stress, which explained 22.8% of the total variation in work stress of nursing staff (F=24.25, P<0.001) . Conclusion: The work stress among nursing staff in Tianjin City is high, the corresponding departments and nursing managers should adopt scientific management methods to reduce the workload of nursing staff according to the influencing factors of work stress, so as to create a good atmosphere for further promoting the healthy development of nursing career and nursing industry in the new era.

Primary cilia support cartilage regeneration after injury / 国际口腔科学杂志·英文版

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Tracing PRX1+ cells during molar formation and periodontal ligament reconstruction / 国际口腔科学杂志·英文版

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1+ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1+ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1+ cells in PDL cells. The behavior of PRX1+ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1+ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1+ cells; during transplanted teeth PDL reconstruction, PRX1+ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1+ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.

Progress in clinical research of congenital membranous cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#Congenital cataract is one of the leading causes of childhood blindness and congenital membranous cataract is a rare and special type of congenital cataract. The lens fibre of congenital membranous cataract is degenerative and its cortex is absorbed gradually. Congenital membranous cataract also has another name, pseudoaphakia, due to the similar phenotype with posterior capsule opacification after cataract surgery, but without intraocular refractive power. There are few reports on congenital membranous cataract at home and abroad, and the research on the pathogenesis of congenital membranous cataract is even less. Clarifying the pathogenesis of congenital membranous cataract, especially the genetics, is very helpful for us to understand the pathogenesis of congenital cataract and the molecular mechanism of lens development.

Primary cilia in hard tissue development and diseases / 医学前沿

Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

LncRNA Nron regulates osteoclastogenesis during orthodontic bone resorption / 国际口腔科学杂志·英文版

Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mice. These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.

Application of micellar electrokinetic capillary chromatography for identification, quantitative detection and unfolding analysis of interleukin-12 / 南方医科大学学报

OBJECTIVE@#To establish a micellar electrokinetic capillary chromatography-based method for identification and quantitative detection of interleukin-12 (IL-12) and analysis of its unfolding process.@*METHODS@#An uncoated fused-silica capillary (inner diameter 50 μm) with a total length of 48.5 cm (40 cm to the detector) was used for the experiment. The factors influencing the separation efficiency of IL-12 were analyzed, and a standard curve of IL-12 concentration was established. The mixture of IL-12 and anti-IL-12 antibody was incubated in a water bath at 38 ℃ for 40 min, and capillary electrophoresis was then performed under the same conditions. The results were compared with those of IL-12 and anti-IL-12 antibody to identify IL-12. IL-12 and dithiothreitol (DTT) were incubated at 60 ℃ in water bath for different lengths of times, and the unfolding process of IL-12 was analyzed based on electrophoresis results of IL-12 in different states.@*RESULTS@#A micellar capillary electrophoresis on-line sweep method was established with 80 mmol/L borate (pH=9.3) containing 30 mmol/L sodium dodecyl sulfate (SDS) as the buffer solution. This system showed a good linear relationship between the peak area and the mass concentration of IL-12 with a linear correlation coefficient of 0.9991 within the linear range of 2 to 120 ng/L. As the incubation time of IL-12 and DTT prolonged, the disulfide bond of IL-12 gradually opened and resulted in distinct changes in the protein peak.@*CONCLUSIONS@#This capillary electrophoresis-based method is simple and sensitive for IL-2 analysis and allows rapid detection of changes in IL-12 content in the setting of tumors and analysis of the possible causes.

Change of Hepcidin in Patients with Iron Overload at the Tibet Plateau / 中国实验血液学杂志

OBJECTIVE@#To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau.@*METHODS@#81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin.@*RESULTS@#The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (β=0.03 ng/ml，95%CI 0.01-0.05) (P<0.01) and BMI (β=5.71 ng/ml，95%CI 0.54-10.88) (P<0.05）.@*CONCLUSION@#Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.

Prevalence and characteristics of clinical Aeromonas isolates carrying mcr-3 gene / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence and characteristics of mcr genes in clinical isolates of Aeromonas spp. in our hospital, and provide reference for clinical analysis of the prevalence and expression of colistin resistance genes. Methods:Polymerase chain reaction (PCR) was used to detect mcr genes in 183 Aeromonas spp. strains. The minimum inhibitory concentrations (MICs) of colistin and polymyxin against mcr-positive Aeromonas spp. were detected by micro broth dilution method. Broth conjugation and filter mating conjugation were performed. Whole genome sequencing was used to analyze the genetic environment of mcr-3 gene in Aeromonas spp.. A recombinant Escherichia coli ( E. coli) DH5α-pGEM-T: : p mcr-3 strain was constructed to verify the expression of mcr-3 gene. Results:The positive rate of mcr-3 gene in 183 strains of Aeromonas spp. was 2.19% (4/183). No mcr-1 or mcr-2 gene was detected among these isolates. Antimicrobial susceptibility test showed that four mcr-3-carrying Aeromonas hydrophilia ( A. hydrophilia) strains were sensitive to colistin and polymyxin (MIC<2 μg/ml). Conjugation experiments indicated that mcr-3 gene could not be transferred between strains. Whole-genome sequencing analysis suggested that the mcr-3 genes carried by the A. hydrophilia isolates belonged to mcr-3.2 and mcr-3-like variants, and no adjacent transfer element was detected upstream and downstream. The recombinant E. coli DH5α-pGEM-T: : p mcr-3 strain was sensitive to colistin (MIC=2 μg/ml). Conclusions:The clinical isolates of A. hydrophilia in our hospital carried mcr-3 gene, but does not exhibit colistin resistance, and no evidence supported the transfer of mcr-3 gene for the time being.

Molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumonia / 中华传染病杂志

Objective:To analyze the molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumoniae ( K. pneumoniae). Methods:From 2011 to 2016, 1 376 strains of K. pneumoniae were isolated from various clinical specimens of hospitalized patients in First Affiliated Hospital of Wenzhou Medical University. Agar dilution method was used to screen out the polymyxin-resistant strains.Polymerase chain reaction (PCR) was used to detect the genes related to polymyxin resistance, and real-time fluorescence quantitative PCR was used to detect the relative mRNA expression level of drug resistant genes. Pulsed-field gel electrophoresis, multilocus sequence typing and Galleria mellonella larvae infection model were performed to analyze the molecular epidemiological and virulent characteristics. Results:A total of 14 strains (1.02%) of polymyxin-resistant K. pneumoniae were detected among 1 376 K. pneumoniae isolates. Subsequent sequencing identified mutations leading to amino-acid changes (K2E, F28C) in MgrB of 10 isolates and D150G in PhoQ of nine isolates, and genes such as mcr and crrB were not detected in all drug-resistant strains. Compared with standard strains, the relative expression levels of pmrH and pmrD mRNA of these drug resistant strains were increased. Analysis of the molecular epidemiology indicated that the 14 drug-resistant strains were divided into nine clones. Galleria mellonella larvae infection model revealed polymyxin-resistant K. pneumoniae isolates had higher virulence. Conclusions:Polymyxin-resistant K. pneumoniae has mutations in mgrB and phoQ genes, and mgrB mutation may play a key role in the change of virulence profiles. The homology among the polymyxin-resistant K. pneumoniae stains in this study is low.

Research progress in regulatory effect of sulforaphane on diabetes and fatty liver disease / 中国药理学与毒理学杂志

The intervention of sulforaphane can reduce the risk of diabetes and its complications. It is mainly achieved by regulating nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit endothelial cell activation and improve high density lipoprotein levels. In addition, sulforaphane can bring about a marked improvement on fatty liver disease by regulating lipid metabolism. Its important pathways include the regulation of peroxisome proliferators-activated receptors y (PPARy), hormone-sensitive triglyceride lipase (HSL) and AMP-activated protein kinase (AMPK) regulation promotes lipolysis. In summary, further exploration of the mechanism of action of plant-derived functional ingredients of sulforaphane may be the key to preventing and treating diabetes and fatty liver disease.

Mesenchymal Stem Cells Attenuate Acute Lung Injury Through Inducing M2 Macrophage Polarization / 中山大学学报(医学科学版)

@#【Objective】 To investigate whether mesenchymal stem cells （MSC）can alleviate acute lung injury by inducing alveolar macrophages to polarize to M2 phenotype. 【Methods】 Umbilical cord MSC was extracted by adherent method and cell phenotypes were analyzed by flow cytometry. The differentiation along osteogenic and adipogenic pathways were assessed by histological staining in vitro. Mouse alveolar macrophage cell line（MH- S cells）which was stimulated by LPS was isolated co-culture with MSC and MSC soluble factor inhibitor was added. We set up three groups （LPS， LPS+MSC ，and MSC inhibitor）. After being cultured for 48 hours ，the macrophage polarization was analyzed by flow cytometry and qPCR. Thirty balb/c male mice were randomly divided into control group（n = 10），ALI group（n = 10）， and ALI+MSC group（n = 10）. LPS was instilled intranasally to establish acute lung injury model in mice. After treatment with MSC for 48 hours ，HE staining of lung tissue was performed for damage assessment. The alveolar lavage fluid （BALF）was obtained and the cells in BALF were analyzed by flow cytometry and qPCR to detect the expression of M2-type macrophage markers including CD206，IL10 and Arg1. The concentration of M1-type macrophage marker TNF-α in the supernatant was measured by ELISA. 【Results】 MSC showed adherent growth and had the ability of osteogenic and adipogenic differentiation. MSC can induce MH- S cells to polarize to M2 type and with a significant increase of CD206 positive proportion cells （P<0.05）. Prostaglandin E2 （PGE2） inhibitors can reverse this effect. Mouse ALI model was successful. After treatment with MSC，the pathology and lung injury score was significantly improved. The proportion of CD206 positive macrophages in alveolar lavage fluid in ALI + MSC group was significantly higher than that in ALI group. The expression of CD206 and IL-10 in mRNA level was significantly higher in ALI+MSC group than that in ALI group. The concentration of inflammatory cytokine TNF- α in alveolar lavage fluid was significantly lower in the ALI+ MSC group than in the ALI group（P<0.05）.【Conclusion】Umbilical cord mesenchymal stem cells can effectively alleviate acute lung injury induced by LPS in mice via PEG2 to induce macrophage to polarize to M2 type.

Correction to: Glycosylation of dentin matrix protein 1 is a novel key element for astrocyte maturation and BBB integrity

In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".

Analysis of HFE and Non-HFE Mutations in a Tibet Cohort with Iron Overload / 中国实验血液学杂志

OBJECTIVE@#The explore the molecular basis of iron-overload in Tibet nationality population of Tibet.@*METHODS@#The inpatients with iron-overload in our department from Dec. 1st 2014 to Jul.31st 2016 were enrolled in this study. Abdominal MRI and the mutation sites C282Y and H63D in HFE exon were examined. For HFE mutation-negative patients, the non-HFE mutation was detected, including 5 HJV mutations of G320V, p.Q312X, p.D249H, p.I281T, p.C321X and 2 TFR2 mutations: (Y250X, I238M), and 2 SLC40A1 mutations: (V162del, N144H).@*RESULTS@#Among 113 iron overload patients, only one showed homozygous p.H63D mutation, and one showed heterozygosis p.H63D mutation. In 73 patients accepted non-HFE gene detection, only one was heterozygosis p.D249N mutation in HJV, and one was heterozygosis p.I238M mutation in TFR2.@*CONCLUSION@#Currently, the pathogenic gene for Tibetan iron-overload has not yet been found.

Correlation of glutamate dehydrogenase with several tumors / 生物工程学报

Most organisms contain glutamate dehydrogenase (E.C. 1.4.1.2-1.4.1.4). In eukaryotes, the enzyme is mainly present in mitochondria. This enzyme plays a vital role in the metabolism of nitrogen and carbon and the signaling pathway. Studies have found that glutamate dehydrogenase has a certain relationship with the occurrence and development of tumors, which is significant for tumor research, but reviews on its relationship with human tumors are rare. This review summarized the relationship between glutamate dehydrogenase and breast cancer, glioma, colorectal cancer and ovarian cancer, etc, thus providing assistance for related research.

Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis / 医学前沿

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.