Objective To investigate the related factor underlying the differential vulnerability of inner hair cell(IHC)ribbon synapses to noise exposure.Methods Twenty-eight C57BL/6J mice were randomly divided into the noise exposure group(NED1)and the control group(CTR)with 14 mice in each group.The noise exposure group was exposed to bandpass noise of 2～20 kHz at 103 dB SPL for two hours while the control group was bred in a quiet environment.Before and after noise exposure,auditory brainstem response was conducted to detect the audi-tory function,whole-mount immunofluorescence staining was used to observe the number of inner hair cell ribbon synapses in different turns.The calcium influx of inner hair cells in the apical and middle turn using whole-cell patch clamp recording was analyzed.Furthermore,the immunofluorescence intensity of calpain in inner hair cells from dif-ferent mouse cochlear turns using whole-mount immunofluorescence staining was compared.Western blotting was used to verify that CtBP2 was degraded by calpain.Results After noise exposure,the ABR threshold of 11.3,16.0,22.6,32.0 kHz increased significantly and the number of ribbon synapses of inner hair cells at the middle turn and basal turn of the cochlea decreased significantly.However,whole-cell patch clamp recordings showed that calcium ion channels were fewer but single-channel current was higher at the apical turn of the cochlea.The open probability of calcium ion channels in IHCs showed no significant difference between the apical turn and the middle turn of the cochlea.But the expression level of calpain of the inner hair cells at the middle and basal turn of the basi-lar membrane was significantly higher than that at the apical turn after noise exposure.The western blotting results also showed that CtBP2 was cleaved in a Ca2+-dependent manner by calpain.Conclusion Calpain may be the main related factor that accounts for the vulnerability of ribbon synapses in inner hair cells in the high frequency region of basal membrane.

Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage,using a combination of morphological analysis,and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL(sound pressure level)broadband noise for 2 hours.Auditory brainstem response(ABR)tests were performed on the mice on days 1,7,14,30,and 90 after the noise exposure.Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses,as well as astrocyte activation levels.In addition,the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed.The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons,indicating that noise caused significant damage to cochlear nucleus neurons.Moreover,a significant loss of auditory synapses labeled with vesicular glutamate transporter 1(Vglutl)was observed,which was the severest on day 14 after noise exposure and slowly recovered on day 90.Interestingly,astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure.By staining with glial fibrillary acidic protein(GFAP),most astrocytes were distributed around the cochlear nucleus,granule cell area,and auditory nerve root before noise exposure,and they had a small size.However,on day 14 after noise exposure,a large number of activated astrocytes aggregated in the ventral cochlear nucleus,and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus,and it is possible that astrocytes are involved in its damage and repair processes.These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis,integration,and neural plasticity in the cochlear nucleus.

Objective: To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) . Methods: We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated. Results: In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) . Conclusion Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.

Objective: To evaluate the prognostic value of serum free light chain ratio (rFLC) and difference (dFLC) in patients with multiple myeloma (MM) . Methods: Clinical data of 479 cases of newly diagnosed MM patients with FLC test records referred to our hospital from January 2012 to March 2016 were collected. rFLC preferred cut-off values were selected as≤14.828,14.828-364.597, ≥364.597 according to the literatures. The dFLC was divided into ≤112.85,112.85-2891.83, ≥2891.83 mg/L three groups. The rFLC and dFLC values among the death, the non-death, the progress and the non-progress groups were compared by t test. The correlation analysis showed that the rFLC and dFLC values were related to the death or progression of the disease. Logistic regression was used to analyze the correlation between each factor and death or progression. Univariate survival analysis (PFS) and total survival (OS) were performed using Kaplan-Meier. Single-variable and multivariate prognostic analysis were performed using Cox model. Results: The cutoff values of rFLC less than 14.828 or dFLC less than or equal to 112.85 mg/L impacted most significant on OS and PFS of the patients (P<0.05) . Different rFLC cut-off values between two groups showed that when rFLC=14.828, OS was significantly better than the other two groups (NR vs 61 & 47 months, P=0.019) ; different dFLC cut-off values between two groups disclosed that PFS and OS were statistically significant when dFLC less than or equal to 112.85 mg/L compared with the other two groups (P<0.05) . The 4-year PFS/OS rates in the initial dFLC≤112.85 mg/L and rFLC≤14.828 groups was significantly higher than of the other two groups. Conclusion Different cutoff levels of rFLC and dFLC might have obviously effects on the prognoses of patients with newly diagnosed MM. The difference of survival prognosis would be more pronounced when rFLC≤14.828 or dFLC≤112.85 mg/L with lower risk of death and lower risk ratio, which might be ideal cutoff value for determining the prognosis of these patients.

Objective To analyze the diagnostic value of multicolor scanning laser imaging (confocal scanning laser ophthalmoscopy, cSLO) combined with swept-source optical coherence tomography (SS-OCT) for lacquer cracks (LC) and myopia stretch lines (MSL) of pathological myopia.Methods A observational study. A total of 83 eyes of 58 patients with pathological myopia were recruited from May 2017 to January 2018 in Department of Ophthalmology of The First People's Hospital Affiliated to Shanghai Jiao Tong University. Among 58 patients, 20 were males (30 eyes) and 38 were females (53 eyes). The mean age was 50.65±12.02 (range from 24 to 70) years old; the average BCVA was 0.37±0.32; the average diopter was?11.38±4.96 D; and the average axial length was 28.91±2.15 mm. All participants underwent FFA and ICGA examination to obtain FFA, ICGA, infrared light reflection (IR) and autofluorescence (AF) images. SS-OCT was applied for scanning macular and optic disc at 9 mm× 9 mm range. cSLO was performed with macular as the center. All images were inspected carefully by three independent observers and the consistency test was detect. LC were diagnosed as hyperreflective line in FFA and hypofluorescent linear lesions in late ICGA. MSL were defined as both hypofluorescent linear lesions in FFA and late ICGA. The accuracy of each inspection item in the diagnosis of LC was detected. The optimal technique was applied with SS-OCT to further explore the detection rate of LC.Results The intra-observer reproducibility was good to excellent for all measurements (Kappa=0.938,P<0.01). The positive detection rate of LC and MSL was highest in the standard images of cSLO (77.1％), followed by SS-OCT red free (73.1％), fundus photography (72.3％), IR (72.3％) and AF (49.4％). The cSLO was optimal in the test consistency (Kappa=0.520,P<0.01) and accuracy (the area under the receiver operating characteristic was 0.750). SS-OCT and cSLO were jointly applied to diagnosis of LC and MSL in high myopia. The positive detection rate of LC, MSL and LC+MSL were 91.7％, 91.2％ and 93.3％respectively. The characteristics of LC in SS-OCT were irregularities and discontinuous of the RPE-Bruch membrane line, discontinuous inner ellipsoid zone, thinner choroid, an increased light penetrance into deeper tissues, and RPE fracture in severe cases. MSL was mainly manifested as RPE clumps, visible large choroidal vessels protruding and pushing the overlying RPE toward the vitreous.Conclusions The diagnosis rate of LC in pathological myopia by cSLO is 77.1％. The standard images of cSLO combined with SS-OCT can diagnose LC, MSL and LC+MSL at rates of 91.7％, 91.2％ and 93.3％ respectively.

Objective To discuss the effect of MST1 (mammalian sterile 20-like kinase 1,MST1) on the prolifera-tion,migration and invasion of SiHa cervical cancer .Methods Western blot was used to detect the expression of MST1 in cervical epithelial cells H8 and cervical cancer cells SiHa;PJ3H-HA-MST1 was constructed and transfect-ed it to SiHa cells by Lipofectamine TM3000;MST1, Ki-67 and MMP9 protein expression were evaluated by Western blot;While the proliferation ,migration and invasion of SiHa cell were assessed by MTS ,scratch adhesion test and Transwell assay respectively .Results Compared SiHa cells with H 8 cells,MST1 expression in SiHa cells was sig-nificantly lower than that in H8 cells.The plasmid was successfully transfected into SiHa cells , MST1 expression was significantly higher , while the expression of Ki-67 and MMP9 was lower .The proliferation , migration and inva-sion ability were all significantly suppressed .Conclusions Overexpression of MST1 can inhibit the proliferation , migration and invasion of cervical cancer cell line SiHa .

Objective To evaluate the relations between hypertensive disorders (HDP) in pregnancy and early-term birth.Methods A total of 3 474 pregnant women were consecutively recruited.Demographic information was collected in early pregnancy.HDP was diagnosed in the first,second and third trimesters,respectively.On the basis of precise evaluation on gestation age,early-term birth was defined as gestational age of 37-38 weeks + 6 days.Logistic regression models were conducted to examine the associations between HDP and early-term birth.Results The current study included 3 260 pregnant women,with the rates of HDP,pregnancy-induced hypertension syndrome and pre-eclampsia as 6.0％ (n=194),4.2％ (n=137) and 1.8％ (n=57),respectively.After controlling for potential confounders,no significant differences between pregnancy-induced hypertension syndrome and early-term birth (OR=1.49,95％C1:0.94-2.36) were found.Pre-eclampsia appeared to have increased the risk of early-term birth (OR=4.46,95％ CI:2.09-9.54).Conclusion Pre-eclampsia could significantly increase the risk of early-term birth.This finding suggested that early detection and intervention programs were helpful in reducing the risk of early-term birth.

OBJECTIVETo explore the efficacy and prognostic factors of induction therapy combined with autogenetic peripheral blood stem cells transplantation (APBSCT)in patients with multiple myeloma (MM).

METHODSFrom January 1998 to May 2015, 201 patients with MM were enrolled. All patients received APBSCT after induction therapy. With the follow up to 20 June 2015, the overall survival (OS), progression free survival (PFS)and prognostic factor were analyzed.

RESULTS① With a media follow up of 36.67 months, the median PFS and OS were 22.87 (17.48- 28.26)and 69.63 (63.57- 75.69)months, 5-year PFS and OS were 17% and 49%, respectively. ②After APBSCT, when the subgroup (n= 112) achieved complete response (CR)compared with the subgroup (n=89) not achieved CR, the median PFS were 32.93 (21.03-44.83) and 18.13 (14.46-21.80) months (P<0.001), respectively; And the media OS were 96.77 (71.79- 121.75)and 54.70 (49.53- 59.87) months (P=0.004), respectively. The risks for disease progression and death declined in CR subgroup. ③ Two subgroups included or not included bortezomib/thalidomide at induction therapy (123 patientsvs 21 patients), the media PFS were 31.67 (24.36- 38.98)and 15.20 (10.11- 20.29) months (P=0.013), respectively; And the media OS were 76.30 (55.44- 97.15)and 52.03 (33.76- 70.30) months (P=0.014), respectively. ④According to the ISS stage, the media OS of stageⅠ, Ⅱ, Ⅲ were 99.47 (59.58-139.36), 66.77 (52.17-81.37), 53.97 (28.71-79.23) (P< 0.001), respectively. The risk for death of stage Ⅱ, Ⅲ were 2.16 and 3.04 times higher than stage Ⅰ, with no difference in terms of PFS. ⑤ The media PFS in IgD (n=22) and IgG (n=101) type MM were 11.17 (10.27- 13.13)and 35.43 (22.69- 48.17)months (P=0.007) , respectively; The media OS were 30.83 (0.24-61.42)and 70.70 (53.52-87.88) months (P=0.039), respectively. The risk for disease progression of IgD type was 2.47 times higher than IgG type. ⑥ Patients received 1 line induction therapy (n=132) compared with more than 1 line (n=69), the media PFS were 25.43 (16.09- 34.77)and 20.27 (15.04- 25.50) months (P=0.042). ⑦Cox analysis showed that CR after APBSCT and ISS stage were independent prognostic factors for OS. IgD type MM and CR after APBSCT were independent prognosis factor for PFS.

CONCLUSIONCR after APBSCT and ISS stage were independent prognostic factors for OS in MM. CR after APBSCT was independent prognostic factor for PFS in MM. However, disease progression more likely occurred in IgD type MM, which was independent negative prognostic factor for PFS in MM.

Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; therapeutic use ; Disease-Free Survival ; Humans ; Multiple Myeloma ; diagnosis ; therapy ; Neoadjuvant Therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Remission Induction ; Survival Rate ; Thalidomide ; therapeutic use ; Transplantation, Autologous ; Treatment Outcome

Objective To observe the effect ofGuanxin-Shutongcapsule in the treatment of arterial elasticity on patients with hypertension.Methods The hypertension patients who met the inclusion criteria were divided into treatment group (50 cases) and control group (52 cases). The control group was treated with antihypertensive drugs to control blood pressure within the normal range. The treatment group was treated withGuanxin-Shutongcapsule on the basis of the control group. All were given 8 weeks treatment. The main artery elastic parameters were meansured by the carotid-femoral pulse wave velocity (C-FPWV) and cervical-dorsal arterial pulse wave velocity (C-DPWV). The immune turbidimetric method was employed to enhance for the determination of high sensitive C reactive protein (hs-CRP); and radioimmunoassay was used to assess the serum IL-6, TNF-a, triglyceride (TG) and total cholesterol (TC). The blood pressure was monitored during the treatment.Results After the treatment, the level of hs-CRP (2.83 ± 1.35 mg/Lvs. 3.65 ± 1.38 mg/L,t=6.357), TNF-α (0.16 ± 0.08 mg/Lvs. 0.28 ± 0.07 mg/L,t=18.213), C-FPWV (13.85 ± 1.86 m/svs. 15.34 ± 1.78 m/s,t=6.524), C-DPWV (11.98 ± 1.45 m/svs. 12.87 ± 1.48 m/s,t=7.152) in treatment group was significantly lower than those in the control group (P<0.01).ConclusionGuanxin-Shutong capsule by inhibiting systemic inflammation, reducing and reversing atherosclerosis, and improving the arterial elasticity and blood pressure.

Objective To quantify the risk factors for aspirin resistance so as to increase the prognosis for risk of coronary heart disease,and to establish a predictive model for aspirin resistance in order to guide the clinical anti-platelet therapy.Methods A total of 938 elderly male patients with stable coronary heart disease (CHD) receiving oral aspirin therapy (＞75 mg/d) over 2 months were included in this study.Their clinical data were collected.Logistic regression analysis was performed to establish a predictive model and risk score for aspirin resistance.Hosmer Lemeshow (H-L) test and an area under the receiver operating characteristic (ROC) curve (the area under the ROC curve) were performed to test the calibration and discrimination of the model.Results Seven risk factors were included in the predictive model,including serum creatinine (＞110 μmol/L:score of 1),fasting blood glucose (＞7.0 mmol/L:score of 1),hyperlipidemia (score of 1),number of coronary arteries in lesion (2 branches:score of 2,≥≥3 branches:score of 4),body mass index[(20-25) kg/m2:score of 2,＞25 kg/m2:score of 4],percutaneous coronary intervention (score of 2),smoking (score of 3).H-L test showed P≥0.05 and the area under the ROC curve＞0.70 in this model.Conclusions the risk factors for aspirin resistance,and establishing a valid predictive model for aspirin resistance,could provide an important reference for anti-platelet therapy in CHD patients.