Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Modified venous grafting to replant an amputated thumb with obstinate arteriospasm / 中华创伤骨科杂志

Objective To evaluate the therapeutic effects of bridging the proper digital artery and the radial artery with a vein graft in replantation of an amputated thumb with obstinate arteriospasm.Methods From June 2011 to May 2017,9 patients received replantation of an amputated thumb at Department of Hand Surgery,The Second Hospital of Tangshan.They were all male,aged from 21 to 55 years (average,39.2 years).Two right thumbs were involved in 2 cases and 7 left thumbs in 7 cases.During replantation,obstinate arteriospasm which could not be alleviated occurred of their bilateral proper digital arteries.A free forearm superficial vein graft was used to bridge the distal end of ulnar proper digital artery of thumb and the radial artery in tabatiere anatomique to establish blood supply by end-to-end or end-to-side anastomosis.At final follow-up,the outcomes were assessed by the tentative criteria set by The Hand Surgery Society of Chinese Medical Association.Results All the 9 replanted thumbs survived with primary wound healing.They were followed up for 6 to 12 months (mean,7.9 months).All the patients were satisfied with the appearance and function of the replanted thumb except that mild atrophy was observed in 2 digits with preoperative rotatory avulsion.According to the tentative criteria set by The Hand Surgery Society of Chinese Medical Association at final follow-up,the outcomes were rated as excellent in 7 cases and as good in 2.The pulp two-point discrimination was between 3 and 8 mm,with an average of 5.3 mm.Conclusions An amputated thumb with obstinate arteriospasm can be replanted by bridging the ulnar proper digital artery of thumb and the deep branch of radial artery using a vein graft to establish adequate blood supply to the replanted thumb,leading to satisfactory efficacy.As the technique is easy,it is worthy of popularization.

Comparing two surgical treatment methods for mucous cysts of the distal interphalangeal joint in elderly patients / 中华老年医学杂志

Objective To contrast and compare two surgical treatments for mucous cysts of the distal interphalangeal joint.Methods Clinical data from April 2004 to January 2016 were retrospectively analyzed.Patients who underwent tumor excision,osteophyte excision,and local flap coverage were assigned into a flap group(n=16),while patients who received osteophyte excision,cyst pedicle resection,and cystic fluid drainage were assigned into a simple osteophyte resection group(n=17).Procedure time,pain,satisfaction score,and hand function were compared between the two groups.Results Patients in the flap group were followed up for 14 to 28 months(mean=19.5 months);the simple osteophyte resection group for 15 to 26 months(mean=20.5 months).There was no recurrence in either group.The rate of excellent efficacy was 81.25 ％ (13/16)for the skin flap group and 82.35 ％ (14/17) for the simple osteophyte resection group,and the difference was not statistically significant(x2=0.007,P ＞ 0.05).Pain relief was achieved in both groups after operation,and the postoperative satisfaction score was higher than the pre-operation score.There was no statistical difference in pre operation pain and satisfaction scores (t 0.14 and 0.35,both P ＞ 0.05),no statistical difference in postoperative pain scores(t =-0.09,P ＞ 0.05),but a statistically significant difference in postoperative satisfaction scores (t =-4.15,P ＜ 0.05) between the two groups.Conclusions Two surgical treatments of mucous cysts can achieve satisfactory aesthetic and clinical outcomes.The simple osteophyte resection method is characterized by a short procedure time and a high level of postoperative satisfaction,but it requires training in microsurgery.Local flap coverage is simple and suitable for lower level hospitals where staff surgeons may lack microsurgical skills,but it may result in certain minor injuries.

Transplantation of flow-through anterolateral thigh flap combined with fibular flap for reconstruction of composite tissue defects at leg / 中华整形外科杂志

Methods@#To explore the transplantation of flow-through anterolateral thigh flap combined with fibular flap for reconstruction of composite tissue defect at leg.@*Method@#12 cases with leg composite tissue defects were reconstructed by flow-through anterolateral thigh flaps combined with fibular flaps. The skin defects ranged from 6 cm×12 cm to 12 cm×20 cm. The bone defects were 4-10 cm in length.The size of flow-through anterolateral thigh flaps was 14 cm×8 cm to 23 cm×13 cm and the fibular osteocutaneous flaps were 6 cm×4 cm to 12 cm×6 cm. The fibular bone was harvested as 7 cm to 13 cm in length.@*Results@#All the flaps survived in 12 cases. Bony reunion was achieved in all the cases. Vascular crisis happened in 2 cases 1 day after operation. Margin necrosis occurred in distal end of one flap, which healed after dressing. All the flaps had soft texture with satisfactory cosmetic and functional result . There was no complication in donor sites.@*Conclusions@#Flow-through anterolateral thigh flap combined with fibular flap can reconstruct soft tissue defect and bone defect simultaneously. It is the ideal method for leg composite tissue defects.

Reconstruction of bone defects of forearm using free vascularized fibular grafts / 中华整形外科杂志

Objective@#To investigate the clinical effect of reconstruction of bone defects of forearm using free vascularized fibular grafts(VFG).@*Methods@#22 patients with bone defects of forearm were treated with free VFG. 6 cases with upper limb bone and soft tissue defects were repaired with free vascularized osteoseptocutaneous fibula as a composite flap. The length of ulna defect ranged from 4 cm to 12 cm and radius defect from 5 cm to 14 cm. The length of harvested fibula ranged from 13 cm to 24 cm. The area of the skin flaps ranged from 12 cm×6 cm to 20 cm×11 cm.@*Results@#All graft bone achieved bone union, with the healing time from 3 to 6 months (mean, 4.5 months). The operation incision healed primarily and all flaps survived with soft texture. All patients were followed up for 12-26 months (mean, 20.5 months). The function of forearm was recovered without refracture. The movement of ankle and the sensation in the leg were normal. According to the Anderson standard at last follow-up visit, the results were excellent in 9 cases, good in 11 cases and fair in 2 cases, with an excellent and good rate of 90.9%.@*Conclusions@#Vascularized fibular grafts VFG is an effective method to repair bone defects of forearm.

A Survey of Allergic Rhinitis among College Students in Kunming / 昆明医科大学学报

Objective To investigate the distribution,epidemiologic feature and the related risk features of allergic rhinitis among college students in Kunming.Methods Stratified cluster sampling was conducted in each school as a unit.The investigated subjects included 1500 students aged from18 to 29 years old from 7 universities in Kunming,Yunnan Province.The epidemiological investigation was carried out using the designed questionnaire of allergic rhinitis.The results were analyzed.Restlts We had given out 1500 questionnaires and the response rate was 98.9％.The self-reported prevalence of allergic rhinitis was 25.4％ among college students in Kunming,in which,the males' prevalence rate was 29.3％ and the females' was 22.9％.And 3.7％ of the students with allergic rhinitis were combined with asthma and the 19.1％ combined with a history of familial inheritance.The main risk factor was dust.Concltsion The self-reported and prevalence of allergic rhinitis among college students in Kunming is 25.4％.Males' prevalence rate is slightly higher than the females'.The potential risk factors are bronchial asthma and the history of familial inheritance.The mainly inducement is dust,animal fur and plant pollen.

Effects of YAP-small interfering RNA on the proliferation and apoptosis of human periodontal ligament stem cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of small interfering RNA (siRNA) targeting YAP on the proliferation and apoptosis of human periodontal ligament stem cells (hPDLSCs).</p><p><b>METHODS</b>Synthesized sequences of siRNA were transfected into hPDLSCs by Lipofectamine™ 2000. The expression of YAP was identified by using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Proliferation activity was detected by using cell counting kit-8 (CCK-8). Changes in the cell cycle and apoptosis rate were detected by using flow cytometry. Results were analyzed by using SPSS 19.0, and P < 0.05 was considered statistically significant.</p><p><b>RESULTS</b>Expression of YAP mRNA and protein were significantly downregulated after 48 h of transfection (P < 0.001). No obvious difference was found in the expression levels of YAP protein between 48 and 72 h, thus indicating that siRNA could inhibit the expression of YAP persistently and effectively. Proliferation activity was inhibited, and apoptosis rate was increased. Cell cycle was changed as the proportion of G₁and S phases increased (P < 0.01) and G₂ phase decreased (P < 0.05).</p><p><b>CONCLUSION</b>Knocking down YAP gene by siRNA could inhibit proliferation activity, induce apoptosis, and change the cell cycle of hPDLSCs. Thus, YAP could regulate the proliferation and apoptosis of hPDLSCs.</p>

Clinical characteristics of bone metastasis from gastric cancer / 中国肿瘤临床

The bone is a common site of metastasis for gastric cancer. High-risk factors of metastatic gastric cancer include young age, poorly differentiated adenocarcinoma, Borrmann type III tumors, depth of invasion at Se and Pm levels, positive lymph nodes, and gastric cancer with concomitant body of stomach cancer. More than half of the transfer pathway belongs to the non-portal system. Cases of gastric cancer with bone metastasis but without liver metastasis accounted for 69%of the total gastric cancer cases, whereas the incidence rate of bone metastasis with lymph node metastasis (≥3 cm away from the primary lesion) was 27%. In addition to the tumor markers human chorionic gonadotropin and carcinoembryonic antigen, radionuclide scan of the bone metastasis provides diagnostic pathways and reliable basis for treatment. Chemoradiation and surgery as symptomatic treatments are alternative therapies for stomach cancer. Bone metastasis confers unfavorable prognosis, and the survival time is often less than six months.

To Investigate Zhang CiGong’s Academic Achievement / 浙江中医药大学学报

Objective To investigate Zhang CiGong who was traditional Chinese medicine doctor and educator ’s academic achievement. [Methods]To summarize and analysize Zhang CiGong’s learning experiences,academic thoughts and examples of clinical experiences. [Results]Zhang CiGong had no prejudice on academic schools, integrated various academic schools’s advantages and then turned into his’s own feature. Zhang CiGong researched and clarified the essence of traditional Chinese medicine theory, and made it flourish. He found the real cause of the disease when treatment,used the holistic approach and syndrome differentiation treatment. He gathered his own experience into the ancients experience and emphasis on practice when he gave Chinese Herbal. [Conclusions]Zhang CiGong’s learning was great and we should learn from him.

Research on the performance comparing and building of affective computing database based on physiological parameters / 生物医学工程学杂志

The validity and reasonableness of emotional data are the key issues in the cognitive affective computing research. Effects of the emotion recognition are decided by the quality of selected data directly. Therefore, it is an important part of affective computing research to build affective computing database with good performance, so that it is the hot spot of research in this field. In this paper, the performance of two classical cognitive affective computing databases, the Massachusetts Institute of Technology (MIT) cognitive affective computing database and Germany Augsburg University emotion recognition database were compared, their data structure and data types were compared respectively, and emotional recognition effect based on the data were studied comparatively. The results indicated that the analysis based on the physical parameters could get the effective emotional recognition, and would be a feasible method of pressure emotional evaluation. Because of the lack of stress emotional evaluation data based on the physiological parameters domestically, there is not a public stress emotional database. We hereby built a dataset for the stress evaluation towards the high stress group in colleges, candidates of postgraduates of Ph. D and master as the subjects. We then acquired their physiological parameters, and performed the pressure analysis based on this database. The results indicated that this dataset had a certain reference value for the stress evaluation, and we hope this research can provide a reference and support for emotion evaluation and analysis.

Effect of Comprehensive Rehabilitation Direction on Functional Ankle Instability / 中国康复理论与实践

@#Objective To investigate the effect of comprehensive rehabilitation direction on functional ankle instability (FAI). Methods 32 consecutive patients with FAI were divided into 2 groups. The rehabilitation group (n=16) finished their rehabilitation program under the instruction of physiotherapists in the hospital, and the control group (n=16) exercised at home by written instruction. All the patients were tested with One Leg Standing Test (OLST) and Foot and Ankle Disability Index (FADI) for the injured ankle before and 4 weeks after training.Results The scores of both OLST and FADI improved after training in the rehabilitation group (P<0.01), but did not in the control group (P>0.05); and improved more in the rehabilitation group than in the control group (P<0.05). Conclusion The comprehensive rehabilitation direction is effctive on FAI.

Preliminary study of diagnosis ofhepatocellular carcinoma by protein chip technique / 肿瘤研究与临床

Obiective To screen serum biomarkers in patients with hepatocellular carcinoma (HCC)by SELDI-TOF-MS technique.Methods SELDI-TOF-MS technique and CM10 Protein Chip were used to detect serum protein patterns of 46 patients with primary hepatic carcinoma and 64 healthy persons.The different proteins were obtained by the Biomarker Wizard software between the patients and healthy persons.The best biomarker of primary hepatic carcinoma was selected by evaluating the sensitivity and specificity of the protein.Results 16 protein peaks were obviously different between the patients and the healthy persons (P ＜0.05).The protein peaks of m/z 6845.70 had the highest diagnosis value with a sensitivity of 89.1％ (41/46)and specificity of 87.5 ％ (56/64).This protein was likely to be a part of the immunoglobulin heavy chain variable region.Conclusion The protein of m/z 6845.70 is potential biomarkers for the diagnosis of HCC.SELDI-TOF-MS technique is a quick,simple,convenient and high through-put technology for diagnosis of hepatocellular carcinoma.

Establishment of gastric cancer model in nude mice / 国际外科学杂志

The establishment of animal model is fundamental to the experimental studies. It involves the selection of animals and cell lines, the determination of the number of cells and the option of the ways of transplant. Only when each production step is operated by following the occurrence and the development mechanism of the gastric cancer, can we simulate the process of growth of the gastric cancer in human body.Due to their congenital immune deficiency, the nude mice serve a better choice for the establishment of gastric cancer animal model. Beyond that, the cell lines selection and transplant way option also play important roles.

Identification of differentially expressed proteins in different ovarian tissues by SELDI-TOF MS / 肿瘤研究与临床

Objective To search for differentially expressed proteins in normal ovaries,benign,borderline and malignant ovarian tumor protein. Methods The protein from ovarial carcinoma tissue and benign ovary was drawn, and analyzed with SELDI-TOF MS. Results There are some high expression proteins in ovarian cancer tissues: M/Z 15 112.15, 15 296.79, 7560.78, 16 049.39, 7682.06, 7932.30,15 851.32, 4619.68 and 8052.10. Borderline ovarian tumor protein peak were between benign and malignant:M/Z 15 112.15, 15 851.32, 7560.78, 7682.06 and 7932.30. Conclusion There were some differentially expressed proteins in different ovarian tissue. They might lay the molecular basis for the clinical diagnosis and therapy of ovarian cancer.

On intellectual capital management of hospitals / 中华医院管理杂志

Management of intellectual capitals is key to the knowledge management of a hospital and to its core competency as well.Such capitals comprise structural capital,human capital,intellectual property right capital and market capital,which jointly decide the sustainable development advantages of a hospital Contemporary hospitals are expected to promote their knowledge management by means of corporate governance,to manage their human resources guided by tacit knowledge theory,to run their reputation and to integrate their intellectual capitals to achieve efficient management of such capitals.

Clinical Research of Chinese Medicine Inunction Wet Dressing Therapy and Helium Neon Laser in the Treatment of Rheumatoid Arthritis / 中国药房

OBJECTIVE:To observe the clinical efficacy of Chinese medicine inunction wet dressing therapy and helium neon laser in the treatment of rheumatoid arthritis.METHODS:Both groups received Methotrexate tablets,Salazosulfapyridine tablets,Loxoprofen tablets.Observation group were additionally treated with Chinese medicine inunction wet dressing therapy and helium neon laser with a treatment course of 30 days.RESULTS:The effective rate was 70.00% for control group and 93.55% for observation group,there was significant difference between two groups(P

MICROVASCULATURE OF THE HUMAN LUNG / 解剖学报

The microvasculature of the lung of three humans was studied with the replicascanning electron microscopic method. The pulmonary arteriole belongs to microvasculature at the level of the respiratory bronchiole and gives out some side branches to the alveoli. The diameter of the arteriole is about 30-50 ?m. The arteriole divided into terminal arterioles, which accompanied with primary alveolar ducts. The diameter of the terminal arteriole is about 10-20 ?m, 17.35?1.62 ?m in average (n=30). There are obvious imprints of smooth muscles and endothelial nuclei on the surface of the casts of arteriole and terminal arteriole. The diameter of the alveolar capillary is 5.87?0.90 ?m in average (n=500). The proportion of the capillary area arround the alveole is 66?1.4%. There are two patterns of capillary network, i. e. long mesh and round mesh in type. The diameter of the mesh is (9.24?2.02)?(5.65?1.40) and 5.75?0.84 ?m, respectively. The distance of the mesh center is 17.13?1.74 ?m (long) and 11.52?1.12 ?m (short) in long mesh, and 11.63?0.88 ?m in round mesh. The capillary network of the long mesh located at the entrance and the base of the alveoli; and the round mesh in the area between them. The metaarteriole supplying the alveoli enters the alveoli at their entrance and thev venule draining the alveoli at their base. The distance between them is about 330 ?m.According to the microvascular architecture, the pulmonary microvasculature may be divided into three ordered units: i. e. the alveolar, the alveolar duct, and the respiratory bronchiolar units.

A STUDY OF THE VERTICAL STRESS ON SEMILUNAR CARTILAGE MODEL USING THREE-DIMENSIONAL PHOTOELASTIC METHOD / 解剖学报

The characteristic of stress and load transmission in the semilunar cartilage model was studied with three-dimensional photoelastic method based on the principle of biomechanics. In addition to the liner function, the menisci may also provide with significant load-bearing capacity, The bearing capacity of external semilunar cartilage is larger than that of the internal one. Besides, the capsule and other soft tissue of the knee joint also participate in the load transmission. This study suggests that application of three-dimensional photoelastic method for the semilunar cartilage research may be a useful mean and with widespread prospect.