Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Mice ; Animals ; Micrognathism ; Masseter Muscle ; Mandible ; Osteogenesis

Objective:To compare the efficacy of pericapsular nerve group (PENG) block combined with lateral femoral cutaneous nerve (LFCN) block versus fascia iliaca compartment block (FICB) in elderly patients undergoing total hip arthroplasty under general anesthesia.Methods:Fifty-eight patients of both sexes, aged 65-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective direct anterior approach to total hip arthroplasty, were divided into 2 groups ( n=29 each) using a random number table method: PENG block plus LFCN block group (PL group) and FICB group (F group). In group PL, the mixture (20 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 3.3 mg was injected around the nerve innervating the hip joint capsule under ultrasound guidance.In group F, the mixture (30 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 5 mg was injected around the nerve innervating the fascia iliaca compartment under ultrasound guidance.All the patients received patient-controlled intravenous analgesia with oxycodone after surgery.When visual analogue scale scores≥4 points, oxycodone 1 mg was intravenously injected as rescue analgesic.The intraoperative consumption of remifentanil was recorded.First time to ambulation, discharge destination, length of hospital stay, and effective pressing times of analgesic pump, requirement for rescue analgesia and the incidence of quadriceps weakness, nausea and vomiting and nerve block related complications within 48 h after surgery were recorded. Results:Compared with F group, intraoperative consumption of remifentanil was significantly decreased, effective pressing times of analgesic pump and incidence of quadriceps weakness were decreased, first time to ambulation and length of hospital stay were shortened, and first discharge destination was prolonged ( P<0.05), and no significant change was found in the requirement for rescue analgesia and the incidence of nausea ( P>0.05) in group PL. Conclusion:PENG block combined with LFCN block can reduce intraoperative consumption of opioids, be helpful for inhibiting postoperative pain sensitivity, and improve early recovery than FICB when used for total hip arthroplasty under general anesthesia.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective To explore the nursing effect of modified prone position and traditional prone position in the skin protection of patients with prone position in ICU. Methods A total of 60 ICU patients with prone position treatment were selected in June 2014 to May 2015. According to the digital method the patients were randomly divided into the control group and the experimental group with 30 cases in each.The control group adopted traditional way of prone position with the head and chest pad pushed up. used by patients not pad up way of improvement of prone position. The incidence of skin pressure injury and the incidence of stress in the two groups were compared. Results The incidence of skin pressure injury was 20.0％(6/30) in the experimental group and 66.7％(20/30) in the control group, and the difference was statistically significant (χ2=13.30, P < 0.05). Conclusions Modified prone position has obvious advantages in reducing the incidence of skin pressure ulcer and is suitable for patients with clinical prone position.

Objectives To implement the guideline-based clinical practice program for identification and manage-ment of dysphagia in stroke patients,and to create a good evidence-based practice culture,and to improve the quality of clinical care. Methods In this study,we use the Iowa model of evidence-based practice as a guide, reference guide issued by RNAO to implement the corresponding implementation strategy tool,and gradually apply the program to the pilot ward. Results The implementation of the program had a positive impact on the patient level (quality of life,satisfaction and hospitalization),the nurse level(satisfaction and knowledge),and the level of eachau-ditcriteria. Conclusion It is possible to improve the clinical nursing quality by adapting the high quality guide-lines for the identification and management of dysphagia in foreign countries and this study can provide reference for the research of future guideline implementation.

Objective To compare the consistency between interstitial fluid glucose and arterial blood glucose in septic shock patients with different tissue perfusion levels.Methods A prospective investigative study was conducted. Sixty-one septic shock patients with ages above 18 years old admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from April 2013 to December 2013 were enrolled. The real-time continuous glucose monitoring system (RTCGMS) and arterial blood gas analyzer were used to measure the patients' interstitial fluid glucose and arterial blood glucose, and according to the criteria of International Organization for Standardization (ISO) and the median of relative absolute difference (Median RAD), the consistency between interstitial fluid glucose and arterial blood glucose was calculated. Based on the lactate (Lac) level and pulse oxygen perfusion index (PI), the septic shock patients were divided into groups with different degrees of tissue perfusion, the consistency between the interstitial fluid glucose and arterial blood glucose among septic shock patients with different degrees of tissue perfusion was compared by using Bootstrap re-sampling technique.Results Negative correlation existed between PI and Lac (r= -0.272,P < 0.001), which showed the opposite change tendency of organism tissue perfusion. In patients with Lac > 8 mmol/L, their consistency between interstitial fluid glucose and arterial blood glucose was better than that in those with Lac > 2-4 mmol/L, and the 95% credibility intervals (CI) of ISO standardized deviation value was 0.026-38.710 (P < 0.05). In patients with PI ≤ 0.7%, their consistency between interstitial fluid glucose and arterial blood glucose was better than that in those with PI > 0.7%-1.4%, the 95%CI of median RAD difference value was 0.002-0.076, and the 95%CI of ISO standardized deviation value was -27.000 to -0.583 (allP < 0.05); in patients with PI > 3.0%, their consistency between interstitial fluid glucose and arterial glucose was better than that in those with PI ≤ 0.7%, PI > 0.7%-1.4% and PI > 1.4%-3.0%, and the 95%CI of ISO standardized deviation values were 3.322-28.302, 11.988-40.265 and 5.170-33.333 respectively (allP < 0.05).Conclusions When septic shock patients were under low tissue perfusion (Lac > 8 mmol/L or PI ≤ 0.7%), the worse the tissue perfusion, the better the consistency between interstitial fluid glucose and arterial blood glucose; when septic shock patients were under normal local tissue perfusion (PI > 3.0%), the better the local tissue perfusion, the better the consistency between interstitial fluid glucose and arterial blood glucose.

Objective To evaluate the efficacy of wax therapy for diabetic peripheral neuropathy, in order to provide suggestions for treatment and prevention.Methods Cochrane Library, JBI, PubMed, EMbase, CBM, CNKI, WANFANG DATA, VIP were searched by computer from inception to October, 2016 for randomized control trails in wax therapy for diabetic peripheral neuropathy. Two researchers searched and selected articles independently and the quality was assessed in accordance with Cochrane Manual. The articles were analyzed with Review Manager 5.3, and the evidence quality was assessed with GRADE profiler 3.6.1 software.Results A total of 8 randomized controlled trials were included. The number of literature quality grade A of original research is 3, while the number of literature quality grade B of original research is 4,and the number of literature quality grade C of original research is 1. Meta-analysis showed that the sensory nervus peronaeus conduction velocities improved by wax therapy for diabetic peripheral neuropathy patients,[MD=2.51, 95%CI(1.35,3.66), P<0.01]. By the GRADE system grading, the evidence quality is moderate.Conclusions The effect of wax therapy for diabetic peripheral neuropathy can improve the sensory nurve conduction velocities and speed of blood circle, so as to prevent ulcer of diabetic feet. Therefore, the clinical curative effects of the therapy require large-sample and high quality studies to confirm.

Objective To analyze the relationship between nursing work environment and nurses′work values of tertiary public hospitals in Tianjin ,and provide a scientific basis for the development of nurses′work values. Methods The sample was 1 875 clinical nurses from 7 tertiary public hospitals in Tianjin, and investigated with Practice Environment Scale (PES) and Work Values Scale. Results The score of nurses′ work values and each dimension(material work values, affective work values,cognitive work values) were different in different level of work environment,betterwork environments>mixedwork environments>poorwork environments(F=121.528, 38.555, 86.834, 136.816,P<0.01). The nursing work environment was positively correlated with work values(r=0.127-0.423, P<0.01). Foundation for quality of care and leadership of the head nurse could predict the nurse work values, and could explain 16.9%of the nurse work values(F=191.315,P<0.01). Conclusions By improving nursing work environment, especially in foundation for quality of care and leadership of the head nurse,can promote the development of nurses′work values.

Objective:To characterize the clinical and epidemiological changes, treatments, and prognoses of primary esophageal small cell carcinoma (PESC). Methods:A retrospective analysis was conducted using the clinical epidemiology data of 529 PESC patients se-lected from the clinical databases of 500,000 esophageal and gastric cardiac carcinomas of the Henan Key Laboratory for Esophageal Cancer Research (1992-2015). Among these patients, 241 cases were included in the survival analysis. The five-year survival rate was calculated using Kaplan-Meier analysis, and the differences in survival rates were compared using the Log-rank analysis model. Re-sults:All 529 PESC cases were analyzed, which accounted for 0.2%of esophageal cancers diagnosed in the same period. The incidence of PESC increased annually (R2=0.574). The survival rates for 1-, 2-, 3-, and 5-year of 241 PESC patients were 55%, 40%, 29%, and 9%, respectively, and the median survival time was 21.9 months. On the basis of the VALSG criteria of lung small cell carcinoma, a statisti-cal difference was observed in the overall survival rates for limited and extensive diseases (P=0.003), with the median survival time of 24.3 and 17.5 months, respectively. Furthermore, significant differences were observed on survival with various treatment modalities (P=0.004). The median survival time of PESC patients treated with combined surgery and radiochemotherapies (28.8 months) was lon-ger than those with either chemotherapy (17.8 months, P=0.015) or chemoradiotherapy (14.5 months, P=0.004). In limited disease pa-tients, the median survival time was longer in patients treated with surgery (27.7 months) than in those without surgery (16.2 months, P=0.007). Notably, the biopsy diagnosis before surgery for PESC was only 40.8%. Conclusion:PESC is a rare malignant carcinoma with increasing incidence. PESC presents poor prognosis, and the survival rate can be improved through combined therapies based on sur-gery. A high misdiagnosis rate for PESC is observed before surgery with biopsy.