Objective To investigate the effects of Wuling Powder on insulin resistance of C57BL/6J mice induced by high lipid diet, and discuss the mechanism. Methods C57BL/6J mice were randomly divided into six groups:normal group, model group, rosiglitazone group, Wuling Powder in low, middle, and high dose groups, 10 mice per group. Besides the normal group, other five groups were fed with high fat and sugar diet, with a purpose to establish insulin resistance model. Normal group and model group were given pure water. Rosiglitazone group received a gavage with rosiglitazone of 0.75 mg/kg. Wuling Power low, middle, and high groups received gavage with Wuling Power of 1.23, 3.69, 11.07 g/kg, respectively, the does volume was 0.2 mL/10 g, once a day. The weight and abdominal girth were detected every week. At the end of the sixth week, mice were given 12-hour fasting, and their eyeball were taken for blood. The body weight, length, and fat in abdomen and both kidneys were detected. Paraffin section was made with HE staining. FPG and FINS of each group were detected. ISI and IRI were calculated, and TC and TG were detected. Results Compared with the model group, Wuling Powder can significantly reduce the body weight and abdominal girth of mice (P<0.01, P<0.001), improve liver fatty degeneration, lower the FPG, FINS, TCH, TG, IRI, and increase the ISI in mice (P<0.05, P<0.01). Conclusions Wuling Powder has the effect of preventing insulin resistance of C57BL/6J mice induced by high lipid diet.

Objective To study exogenous expression and subcellular localization of wild type (WT ) and mu-tant PAX3 proteins in vitro by generating their expression plasmids for further study of pathogenesis of Waarden-burg syndrome (WS) .Methods The plasmids pECE-PAX3 and pcDNA3 .0-HA were ligased after they were cut by double enzyme digestion using molecular cloning technique to generate recombinant eukaryotic expression plasmid pcDNA3 .0-PAX3-HA ,which was as a template to generate expression plasmids pcDNA 3 .0 -H80D -HA and pcDNA3 .0-H186fs-HA of novel mutations H80D and H186fs of PAX3 gene .All constructs were verified by di-rect nucleotide sequencing .NIH3T3 cells were transfected transiently with the expression plasmids of PAX3 ,H80D and H186fs respectively .The exogenous expression of WT PAX3 protein and mutant H80D ,H186fs proteins were analysed using Western blot assay ,while their subcellular distribution were observed using immunofluorescence as-say .Results The DNA sequences of expression plasmids of PAX3 and its mutant H80D ,H186fs were correct . Both WT and mutant PAX3 proteins were detected at the expected size .WT PAX3 and H80D proteins were only lo-calized in the nucleus ,whereas H186fs protein showed aberrant localization in both cytoplasm and nucleus .Conclu-sion We successfully generated the recombinant eukaryotic expression plasmids of PAX 3 gene and its mutants and drew preliminary conlusion of gene mutation having effect on subcellular distribution of WT PAX 3 proteins in vitro , which lays experimental basis for further study of the moceluar mechanism of WS caused by PAX3 gene mutations in China .

OBJECTIVE: To explore the effect of masking therapy for the early stage of the patients with noise-induced tinnitus,and imply the treatment for patients with noise-induced tinnitus. METHOD: Sixty-eight cases with tinnitus were studied. All the patients took the audiological examinations and tinnitus tests firstly, and accepted the masking therapy for 6 months. The therapeutic effiency was evaluated according to tinnitus handicap inventory (THI) and subjective visual-analogue scale (VAS). The minimum masking intensity was also evaluated. RESULT: The majority of the patients with noise-induced tinnitus (59 cases, 86. 8%) had tinnitus frequency of 4 kHz,and most of them (44 cases, 64. 7%) had positive residual inhibition tests. Tinnitus completely disappeared in 3 cases after masking therapy, and the efficiency of this treatment is 83. 8%. There was significant difference in the scores of THI and VAS before and after therapy(P<0. 01), and there was also significant difference in the minimum masking intensity (P<0. 01). CONCLUSION Masking therapy is the most important treatment for the patients in the early stage of noise-induced tinnitus. The therapeutic effiency is significant and should be promoted.
Humans ; Noise ; adverse effects ; Tinnitus ; etiology ; therapy

OBJECTIVE: To analyze and summarize nystagmus of patients with posterior canal benign paroxysmal positional vertigo (BPPV) in positioning test,and to improve the diagnosis and treatment of posterior canal BPPV (PSC-BPPV). METHOD: The present study was conducted on 175 patients who had unilateral BPPV of the posterior semicircular canal (PSC). Their positional nystagmus recorded by videnonystagmography in Dix-Hallpike test,roll test and roll over test were analyzed to summarize the characteristics of nystagmus on nystagmograph of PSC-BP-PV. RESULT: Of the 175 patients, lesion was located in the left PSC in 69 (39.4%) patients,the right PSC in 106 (60. 6%)patients. The nystagmus of patients with PSC-canalithiasis showed upward on the vertical phase of nystagmograph and orientated the different side on horizontal phase in the head hangging position. The horizontal phase pointed to the contralateral side in 47(26. 9%) patients, the ipsilateral contralateral side in 100(57. 1%) patients,no significant reverse ingredients in 28(16.0%) patients. When these patients returned to sit,139(79.4%) patients showed down beating positioning nystagmus, whereas 36 (20. 6%) patients with no nystagmus only had a short vertigo or dizziness. The horizontal phase of the 139 patients pointed to the contralateral side in 40(22. 9%) patients,the ipsilateral contralateral side in 68(38. 9%) patients,no significant reverse ingredients in 31(17. 7%) patients. In roll test,12 patients of the right PSC-BPPV presented an up-beating rotatory nystagmus when the head turned to right,and 5 patients of the left PSC-BPPV presented a down-beating rotatory nystagmus when the head turned to left. When the patients changed body from the left lateral position to the right lateral position in the roll over test, 74(42. 3%) patientsshowed vertical positioning nystagmus. In 30 patients who presented an up-beating nystagmus, there were 25(83. 3%) patientscame from the right PSC-BPPV. In 44 patients who presented a down-beating nystagmus, there were 36(81. 8%) patientscame from the left PSC-BPPV. The direction of the vertical nystagmus was highly correlated with the judgment about the side of the PSC-BPPV in roll over test (P<0. 01). CONCLUSION The patient with PSC-canalithiasis showed an uncertain direction in torsional nystagmus in Dix-Hallpike test,the diagnosis was mainly concern with the vertical nystagmus. When we found a rotatory nystagmus with much more up-beating nystagmus in roll test, it might be PSC-BPPV. We also can use the roll over test to diagnose the location of the otolith in which side of the PSC-BPPV.
Benign Paroxysmal Positional Vertigo ; complications ; Dizziness ; Electronystagmography ; Face ; Head ; Humans ; Nystagmus, Physiologic ; Otolithic Membrane ; Patient Positioning ; Semicircular Canals ; Vertigo ; Vestibular Function Tests

OBJECTIVETo explore the pathogenetic mechanism of a family affected with Waardenburg syndrome.

METHODSClinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively.

RESULTSA heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITFand mutant MITFwere confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm.

CONCLUSIONThe c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.

Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Mutation ; genetics ; Pedigree ; Waardenburg Syndrome ; genetics ; Young Adult

Primary pulmonary synovial sarcoma is a rare pulmonary malignant tumor originated from primitive mesenchymal, which has short overall survival and poor prognosis. Related case reports are lacked at home and abroad. In recent years, the development of targeted therapy has brought remarkable benefits to cancer patients. Apatinib (Hengrui Pharmaceutical Co. Ltd, Jiangsu, People's Republic of China) is a small molecule vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which selectively inhibits VEGFR-2 and blocks the VEGF signal pathway, then strongly inhibiting the tumor angiogenesis. Apatinib has shown favorable therapeutic effect and acceptable toxicity on various tumors. Here we report a case of primary pulmonary synovial sarcoma with postoperative multiple metastases treated with apatinib, in order to provide a new considerable treatment.
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Humans ; Lung Neoplasms ; drug therapy ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Metastasis ; Postoperative Period ; Pyridines ; therapeutic use ; Sarcoma, Synovial ; drug therapy ; pathology ; surgery

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers.
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Animals ; Antineoplastic Agents, Immunological ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; genetics ; immunology ; Humans ; Immunotherapy ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; genetics ; metabolism