Objective To evaluate the safety of Ad-Mathl administration to inner ear and provide the base data for vestibular dysfunction gene therapy.Methods Ten mature Wistar rats were divided into normal control group(srats) and adenovirus(E1,E3-Deleted and carried mathl and enhanced green fluorescent protein report gene,Ad-Mathl-EGFP)scala vestibuli transfer group(5 rats).Right ears of the Ad-Mathl-EGFP transfering group rats were deliveried 5ul Ad-Mathl-EGFP(physieal tite 2.1 10~(11)v.P./ml)into cochleas through the way of drilling scala vestibuli of cochlear basal turn.As a control,the normal group received nothing to inner ear.In order to estimate functional condition of vestibule and cochlea,the click-evoked potentials on the surface of the cervical dura mater(CDM-CEP),auditory brain stem response(ABR)and swimming time were recorded in all rats at 7 days after treatment,and then histologic and morphologic observation were carried out after animals were sacrificed.Results All animals' morphologic observation showed that inner ear hair cells were normal after transfer.Seven days after transfer,the swimming time was 4.0±0.71 s in normal control group and 5.0±0.71 s in scala vestibuli delivery group.The threshold of CDM-CEP and ABR were 85±3.54 dB SPL and 37±4.47 dB SPL in normal control group,and 89±6.52 dB SPL and 40±3.54 dB SPL in Ad-Mathl-EGFP scala vestibuli delivery group,respectively.There was no significant difference existed between control group and Ad-Mathl-EGFP scala vestibuli delivery group.Conclusion The Ad(E1,E3-Deleted)is safe for vestibular and cochlea hair cells and can be used as an ideal vector of gene transfer.

Objective To investigate the clinical efficacy of aprepitant in the treatment of cisplatin based chemotherapy in-duced nausea and vomiting.Methods The tumor patients treated with cisplatin(80 mg/m2)chemotherapeutic regimen in Affiliated Shantou Hospital of Sun Yat-Sen University from December 1,2014 to December 1,2016 were selected,61 cases still had vomiting after using granisetron and dexamethasone for routinely stopping vomiting,the patients with aprepitant and dexamethasone for fur-ther stopping vomiting served as the aprepitant group,while the patients with granisetron and dexamethasone as the granisetron group.Then the complete response(CR)rates within 24,24-72,>72-144 h were observed in the two groups.Results The CR rates within 24 h in the aprepitant group and granisetron group were 66.67% and 51.61% respectively,the difference was not sta-tistically significant(P=0.232),which at 24-72 h were 80.00% and 54.84% respectively,the aprepitant group was significantly better than the granisetron group(P=0.036),which at >72-144 h were 86.67% and 64.52% respectively,the aprepitant group was better than the granisetron group(P=0.045).The comparison of adverse reactions between the two antiemetic drugs found that constipation,diarrhea,urticaria,fatigue and anxiety had no significant difference(P>0.05),the occurrence rate of total adverse reactions in the aprepitant group was 23.33%,which in the granisetron group was 25.81%,the difference between the two groups was not statistically significant(P>0.05).Conclusion Aprepitant combined with dexamethasone has better effect for treating hy-peremetic chemotherapy drug cisplatin chemotherapy caused nausea and vomiting with good tolerance.

Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.

Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.