Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.

Objective To explore the mechanism of ferroptosis induced by endoplasmic reticulum stress(ERs)in acute respiratory distress syndrome(ARDS).Methods In order to determine the effects of LPS on oxidative stress and Fe2+level of mouse capillary alveolar epithelial cells(MLE12 cells),the cells were treated with LPS(0,1,2,5 μg/ml)for 24 h.To verify the role of ferroptosis in lipopolysaccharide(LPS)-induced cell death,MLE12 cells were divided into control(Con)group,iron removal inhibitor(Fer-1)group,LPS group and LPS+Fer-1 group.LPS+Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,then the cells were exposed to 5 μg/ml LPS for 24 h.Con group was treated with solvent DMSO for 24 h.Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,and then treated with DMSO for 24 h.The cells in LPS group were exposed to 5 μg/ml LPS for 24 h.The MLE12 cells were divided into three groups:Con+Vector group,Con+sequence similarity family 134 mem-ber B(FAM134B)group,LPS+Vector group and LPS+FAM134B group.After transfected with vector or FAM134B overexpression plasmid for 48 h,the cells were exposed or not exposed to 5 μg/ml LPS for 24 h.Cell vi-ability was measured by CCK-8.The levels of malondialdehyde(MDA),glutathione and iron,the protein levels of ferroptosis markers[cyclooxygenase 2(PTGS2),glutathione peroxidase 4(GPX4)]and ERs markers[glucose reg-ulatory protein 78(GRP78),activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)]were measured in different groups.In order to further confirm the results of in vitro cell experiments,40 mice were randomly divided into Con+Vector group,Con+FAM134B group,LPS+Vector group and LPS+FAM134B group,with 10 mice in each group.LPS-induced sepsis models were established in LPS+Vector group and LPS+FAM134B group,and the levels of GPX4 and ERs in lung tissue were evaluated by immunofluorescence staining and protein blot.Results LPS treatment increased the levels of PTGS2 and MDA,and decreased the levels of GPX4 and GSH in MLE12 cells in a dose-dependent manner.Compared with LPS group,the cell viability,GPX4 and GSH levels in LPS+Fer-1 group increased significantly(P<0.05),while the PTGS2 protein level and MDA level decreased significantly(P<0.05).Compared with LPS+Vector group,LPS+FAM134B group significantly increased cell viability(P<0.05),decreased PTGS2 protein level(P<0.05)and increased GPX4 level(P<0.05).At the same time,the level of MDA in LPS+FAM134B group was lower than that in LPS+Vector group(P<0.05),and the level of GSH was higher than that in LPS+Vector group(P<0.05).In animal experiment,compared with LPS+Vector group,the expression levels of 4-HNE,ATF4 and CHOP in lung tissue of LPS+FAM134B group decreased significantly(P<0.05),and the expression levels of GPX4,FAM134B group in-creased significantly(P<0.05).Conclusion LPS induces ferroptosis and ERs in MLE12 cells in a dose-depend-ent manner.Activating the endoplasmic reticulum autophagy associated FAM134B receptor helps to inhibit ERs and alleviate cell ferroptosis.

AIM To study the chemical constituents from the roots of Pfaffia glomerata(Spreng)Pedersen.METHODS The 95%and the 50%ethanol extract from P.glomerata were isolated and purified by silica gel,D101 macroporous resin,sephadex LH-20,polyamide,ODS,preparative HPLC and recrystallization,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1,2,4-benzenetriol(1),polypodine B(2),(-)-syringaresinol-4-O-β-D-glucopyranoside(3),poststerone(4),stachysterone B(5),calonysterone(6),taxisterone(7),makisterone C(8),20,22-O-(R-ethylidene)-20-hydroxyecdysone(9),20,22-O-(R-3-methoxycarbonyl)propylidene-20-hydroxyecdysone(10),shidasterone(11),5α-20-hydroxy-ecdysone(12),abutasterone(13),25-hydroxydacryhainansterone(14),methyl-α-D-fructofuranoside(15),methyl-β-D-fructofuranoside(16),chikusetsusaponin Ⅳamethyl ester(17),uridine(18).CONCLUSION Compounds 1-6,8-16,18 are isolated from P.glomerata for the first time,and compounds 1,3-6,8-16,18 are isolated from the genus of Pfaffia for the first time.

AIM To study the chemical constituents from the ethyl acetate fraction of Baccharis trimera(Less.)DC.METHODS The ethyl acetate fraction of B.trimera was isolated and purified by macroporous resin D101,Sephadex LH-20 gel,silica gel and other chromatographic techniques,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as 15,16-epoxy-15α-methoxy-ent-clerod-3-en-18-oic acid(1),13-epi-15,16-epoxy-15α-methoxy-ent-clerod-3-en-18-oic acid(2),methyltrineracetal(3),epimethyltrineracetal(4),trinerolide(5),15-epitrinerolide(6),18-methylmalonyl-7α-hydroxy-meth-yltrineracetal(7),18-methylmalonyl-7α-hydroxy-epimethyltriner-acetal(8),18-methylmalonyl-methyltrineracetal(9),18-methylmalonyl-epi-methyltrineracetal(10),methy 3,5-dicaffeoylquinate(11),8-dimetho-xyflavone(12),4',7-dihydroxy-5-methoxyflavanone(13),4-(3',4'-dihydroxycinna-moyl)-oxy-methy-lcinnamate(14),3',7-dihydroxy-4',6,8-trimethoxy-flavone(15),erigeroflavanone(16),nepetin(17),4,2',4',β-tetrahydroxy-6'-methoxy-α,β-dihydrochalcone(18),eugeniyl-O-β-D-glucoside(19),7-hydroxyl-5,6,3',4'-tetramethoxylflavone(20),phomoxanthone J(21),18-acetyl-7α-hydroxy-methyltrineracetal(22),18-acetyl-7α-hydroxy-epimethyltrineracetal(23).CONCLUSION Compounds 3-10 and 22-23 are epimers isolated from this plant for the first time.Compounds 11-16,18-21 are first isolated from genus Baccharis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To analyze the risk factors for late-onset hemorrhagic cystitis(LOHC)after allogeneic hematopoietic stem cell transplantation(allo-HSCT),the risk factors for the progression of LOHC to severe LOHC,and the effect of LOHC on survival.Methods:The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed.The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis.Then,the differences in overall survival(OS)and progression-free survival(PFS)between different groups were analyzed.Results:The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows:age≤45 years old(P=0.039),intensified conditioning regimen with fludarabine/cladribine and cytarabine(P=0.002),albumin ≤ 30 g/L on d30 after transplantation(P=0.007),CMV-DNA positive(P=0.028),fungal infection before transplantation(P=0.026),and the occurrence of grade Ⅱ-Ⅳ aGVHD(P=0.006).In the transplant patients who have already developed LOHC,the occurance of LOHC within 32 days after transplantation(P=0.008)and albumin ≤ 30 g/L on d30 after transplantation(P=0.032)were independent risk factors for the progression to severe LOHC.The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC(P=0.041).Conclusion:For the patients aged ≤ 45 years old and with intensified conditioning regimen,it is necessary to be vigilant about the occurrence of LOHC;For the patients with earlier occurrence of LOHC,it is necessary to be vigilant that it develops into severe LOHC.Early prevention and treatment of LOHC are essential.Regular monitoring of CMV-DNA and albumin levels,highly effective antiviral and antifungal therapies,and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To analyze the risk factors of Epstein-Barr virus(EBV)infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT)and its impact on survival.Methods:The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed.Patients were divided into EBV(n=114)and Non-EBV(n=233)groups according to whether they were infected with EBV.The incidence of EBV infection after allo-HSCT was calculated,and the risk factors of EBV infection were analyzed.Results:A total of 114(32.8％)patients presented EBV infection(all peripheral blood EBV-DNA were positive).EBV infection occurred in 88 patients within 100 days after transplantation,which accounted for 77.2％of all patients with EBV infection.5 cases(1.44％)were confirmed as post-transplant lymphoproliferative disorder(PTLD).The median onset time of patients was 57(7-486)days after transplantation.Multivariate analysis showed that the use of ATG/ATG-F,occurrence of CMV viremia,and grade Ⅲ-Ⅳ aGVHD were risk factors for EBV infection.Furthermore,compared to BUCY,the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection.Conclusion:EBV infection is a common complication after allo-HSCT.Intensified preconditioning regimens,use of ATG/ATG-F,CMV viremia and grade Ⅲ to Ⅳ aGVHD increase the risk of EBV infection after allo-HSCT.

Objective:To analyze the risk factors of primary poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid malignancies and the impact of primary PGF on survival. Methods:The clinical data of 146 patients with myeloid malignancies who underwent allo-HSCT in our hospital from January 2015 to December 2021 were retrospectively studied. Some relevant clinical parameters which may affect the development of primary PGF after allo-HSCT were selected for univariate and multivariate analysis,as well as performed survival analysis. Results:A total of 9 patients (6.16％) were diagnosed with primary PGF,and their medium age was 37(28-53) years old. Among them,1 case underwent matched sibling donor HSCT,1 case underwent matched unrelated donor HSCT,and 7 cases underwent HLA-haploidentical related donor HSCT. Moreover,5 cases were diagnosed as cytomegalovirus (CMV) infection,and 3 cases as Epstein-Barr virus (EBV) infection. Univariate and multivariate analysis showed that CD34+cell dose<5×106/kg and pre-transplant C-reactive protein (CRP)>10 mg/L were independent risk factors for occurrence of the primary PGF after allo-HSCT in patients with myeloid malignancies. The 3-year overall survival (OS) rate of primary PGF group was 52.5％,which was significantly lower than 82.8％ of good graft function group (P<0.05). Conclusion:Making sure pre-transplant CRP≤10 mg/L and CD34+cell dose ≥5×106/kg in the graft may have an effect on preventing the occurrence of primary PGF after allo-HSCT. The occurrence of primary PGF may affect the OS rate of transplant patients,and early prevention and treatment are required.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype