Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective To compare the association of the incidence and mortality of leukemia and the human development index(HDI)in different countries or regions in 2022,and the trend of leukemia incidence and mortality with age in countries with different HDI levels.Methods GLOBOCAN 2022 data related to leukemia incidence and mortality in different countries or regions worldwide and HDI were evaluated by Pearson correlation analysis and Kruskal-Wallis test.The incidence and mortality rates of each age and the age change trend were analyzed using the Joinpoint Regression model.Results Age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and mortality to incidence ratio(M/I)were statistically significantly different among the four groups of HDI countries(P<0.001).HDI was positively correlated with ASIR and ASMR and negatively correlated with M/I.Among all ages,ASIR and ASMR of leukemia of the four groups had similar trends with age,and the risk of leukemia was high at ages less than 15 and more than 40.The incidence of leukemia in all age groups in China differed from those in other countries with high HDI,while the mortality rate was lower than those in other countries with high HDI.Conclusion Countries or regions with higher HDI have higher ASIR and ASMR and lower M/I because of their better medical condition.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective To compare the effects of visual rigid laryngoscope and visual laryngoscope in nasotracheal intubation(NTI)for patients with cervical spine immobilization simulated difficult airway.Methods Ninety patients scheduled for selective surgery under general anesthesia requiring NTI,52 males and 38 females,aged 18-64 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were scheduled for selective surgery under general anesthesia requiring NTI.Before anesthesia induction,the spinal surgeon selected an appropriate cervical collar and adjusted it to fix patient's neck to establishing difficult airway sim-ulation model.All patients were randomly assigned into two groups:visual rigid laryngoscope(group R)and common visual laryngoscope(group C),45 patients in each group.NTI was performed using either visual rigid laryngoscope or visual laryngoscope in groups R and C,respectively.The nasal passage time,glottic exposure time,intubation time,number of successful first intubation attempts,and intubation attempts were recorded.Glottic exposure was assessed using the Cormack-Lehane(C-L)grading system,and the intuba-tion condition was quantitatively evaluated using the modified nasal intubation difficulty scale(NIDS).The blood pressure and heart rate were measured at baseline(T1),immediately after intubation(T2),and at 1 minute(T3)and 3 minutes(T4)after intubation.The occurrence of intubation-related complications(nasal bleeding,sore throat,hoarseness)was recorded.Results Compared with group C,the nasal passage time and proportion of successful intubations without difficulty were significantly increased in group R,and the glottic exposure time and intubation time were significantly decreased in group R(P<0.05).Compared with group C,the HR and MAP at T2 and T3 were significantly decreased in group R(P<0.05).Com-pared with group C,group R had significantly lower incidence rates of nasal bleeding,sore throat,and hoarseness(P<0.05).There were no statistically significant differences in the first intubation success rate,number of intubation attempts,or C-L grade between the two groups.Conclusion Patients with cer-vical spine immobilization simulated difficult airway,both visual rigid laryngoscope and visual laryngoscope can be performed safely and effectively in NTI.Compared with visual laryngoscope,visual rigid laryngoscope can provide faster glottic exposure,shorter intubation time,lower intubation difficulty,less hemodynamic impact,and lower incidence of complications.

Objective:To investigate the correlation between residual cholesterol (RC) and carotid intima-media thickness (cIMT) in non-diabetic population.Methods:Non-diabetes population received health examination in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from January 1, 2018 to December 31, 2021 were retrospectively included. According to the carotid ultrasound results, they were divided into cIMT thickening group (≥1 mm) and non-thickening group (<1 mm). The RC level was calculated according to total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Multivariate logistic regression analysis was used to determine the correlation between RC and cIMT. Results:A total of 1 803 non-diabetes subjects, aged 58.3±15.6 years, including 1 100 males (61.0%), were enrolled. There were 916 patients (50.8%) in the cIMT thickening group and 887 (49.2%) in the non-cIMT thickening group. Compared with the non-cIMT thickening group, cIMT thickening group had significantly higher proportion of male, hypertension, hyperlipidemia, atrial fibrillation, past stroke history, smoking and alcohol consumption, as well as significantly higher age, blood glucose, triglyceride, RC, TC and LDL-C, and significantly lower HDL-C (all P<0.01). Multivariate logistic regression analysis showed that RC was independently associated with cIMT thickening ( Ptrend<0.001). Conclusion:RC is associated with cIMT thickening in non-diabetes population.

To establish a disease risk prediction model based on genetic susceptibility genes and environmental risk factors， which can target high-risk population as early as possible， and intervene in the environmental risk factors in this population. Moreover， accurate screening of genetically susceptible populations can enhance the efficiency of health system. In recent years， with the maturation and cost reduction of high-throughput gene testing， gene testing has been widely used in individual clinical decision-making and will play a more important role in medical and health decision-making. The correlation between genetic testing and disease risk prediction is increasing， making it a prominent research topic in this field. This review summarizes the approaches for establishing and evaluating risk prediction models and discusses potential future challenges and opportunities.

Corona virus disease 2019 （COVID-19） has led to more than 500 million cases， including 6.19 million deaths. Mutated strains of SARS-CoV-2 （alpha， beta， gamma， delta and omicron） have successively emerged. Currently the omicron variant is gradually replacing the delta variant， driving a surge of cases in most countries including China， posing a great challenge to the prevention and treatment of COVID-19. In the face of the severe pandemic situation， a large number of non-medical volunteers are fighting on the front lines of the war against the pandemic and are vulnerable to exposure due to lack of professional knowledge. This paper introduces the routine skills training of volunteers and emergency response， aiming to provide behavioral guidance for non-medical volunteers in designated isolation facilities.

Objective:To investigate the predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis (CVST).Methods:Patients with CVST treated in Drum Tower Hospital Affiliated to Medical School of Nanjing University from January 2008 to March 2021 were retrospectively enrolled. The risk factors, clinical manifestations, imaging examination and 90 d follow-up data were collected. The complicated intracranial hemorrhage group and non-intracranial hemorrhage group were compared. Multivariate logistic regression analysis was used to determine the independent predictors of intracranial hemorrhage in patients with CVST. Results:A total of 104 patients with CVST were enrolled, including 42 males and 62 females. Their age was 35.24 ± 10.92 years old (range 22-68 years). Thirty-eight patients (36.84%) were complicated with intracranial hemorrhage, including 34 hemorrhagic cerebral infarction and 4 complicated subarachnoid hemorrhage. Univariate analysis showed that compared with the non-intracerebral hemorrhage group, the intracranial hemorrhage group was more common in puerperal/pregnant patients (60.52% vs. 48.48%; P=0.012), with more acute onset (57.89% vs. 48.48%; P=0.004), focal neurological signs (47.37% vs. 19.70%; P=0.003) and seizure (39.47% vs. 18.18%; P=0.017), and the site of thrombosis was more common in the superior sagittal sinus (57.89% vs. 36.36%; P=0.033). Multivariate logistic regression analysis showed that puerperium/pregnancy (odds ratio 2.857, 95% confidence interval 1.095-7.453; P=0.031) and superior sagittal sinus thrombosis (odds ratio 2.847, 95% confidence interval 1.110-7.302; P=0.027) were the independent predictors of intracranial hemorrhage in patients with CVST. The analysis at 90 d after onset showed that there was no significant difference in the good outcome rate between the intracranial hemorrhage group and the non-intracranial hemorrhage group (86.84% vs. 89.39%; P=0.695). Conclusions:Puerperium/pregnancy and superior sagittalsinus thrombosis are the independent risk factors for intracranial hemorrhage in patients with CVST. However, complicated with intracranial hemorrhage is not associated with 90-day clinical outcomes.

【Objective】 To investigate the effect of transfusion-transmitted Zika virus (ZIKV) on the expression of non-coding circular RNA (hsa_circ_0001613) and the role of hsa_circ_0001613 in Zika virus replication. 【Methods】 Human adenocarcinomic alveolar basal epithelial cells (A549) were seeded on a 12-well plate at 1.8×10⁵/ well and infected with ZIKV at 0.05 MOI. The Total RNAs were isolated every day for 5 days after infection, and the relative expression level of hsa_circ_0001613 was detected by qRT-PCR. In addition, 10nM siRNA-hsa_circ_0001613 was transfected into 2×10⁵/ well A549 cells to specifically knock down the expression level of hsa_circ_0001613. 24h later, the cells were infected with ZIKV (MOI=0.05). Total RNAs were isolated at day 1-5 post-infection, proteins were extracted 96h post-infection. ZIKV replication, relative host antiviral gene expression, and interferon stimulated response element (ISRE) activity were tested using qRT-PCR, western blot and dual luciferase assay, respectively. 【Results】 The relative expression of hsa_circ_0001613 decreased significantly after 1-5 days of ZIKV infection. Knockdown of hsa_circ_0001613 inhibited ZIKV replication. Meanwhile, hsa_circ_0001613 knockdown significantly upregulated IFN-α/β and its downstream interferon-stimulated genes (ISGs) expression, also increased ISRE activity. 【Conclusion】 ZIKV infection significantly suppressed hsa_circ_0001613 expression in A4549 cells. Preliminary study indicated that hsa_circ_0001613 knockdown inhibited ZIKV replication possibly through activating type-Ⅰ IFN signaling pathway as showed by increased ISGs expression and ISRE activity.

【Objective】 To investigate the role of non-coding microRNA miR-16-5p in ZIKV replication and the underlying mechanism. 【Methods】 1×10⁵/mL HeLa cells were seeded in 24-well plate and infected with ZIKV(MOI=5). RNAs were harvested, and miR-16-5p expression levels were measured by qRT-PCR at 24, 48 and 72 hour post infection, respectively. HeLa cells were transfected with 20nM miR-16-5p mimic and infected with ZIKV(MOI=5) at 24h post transfection. RNAs were extracted and ZIKV RNA and several inflammation factors expression were tested using qRT-PCR at 48h post infection. HeLa cells were co-transfected with 1μg NFκB-luc and 10ng pRL-TK with 20nM miR-16-5p mimic, and then infected with ZIKV(MOI=5) for 24h before the luciferase expression was tested at 48h post infection. HeLa cells were transfected with 20nM miR-16-5p mimic and infected with ZIKV(MOI=5) at 24h post transfection, and cell apoptosis was assayed through flow cytometry. 【Results】 Compared with uninfected control, miR-16-5p expression was significantly decreased at 24h, 48h and 72h following ZIKV infection. MiR-16-5p over-expression inhibited ZIKV replication, while upregulated NFκB activity and inflammation factors expression compared with the negative mimic-transfected cells. MiR-16-5p overexpression also promoted HeLa cell apoptosis. 【Conclusion】 ZIKV infection downregulated intracellular miR-16-5p expression. Overexpression of miR-16-5p suppressed ZIKV infection. MiR-16-5p inhibited ZIKV replication and promoted cell apoptosis probably by activating NFκB pathway and stimulating inflammation factors expression.