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.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Objective:To explore the effect of the non-suicidal self-injury (NSSI) management plan for hospitalized adolescents with mood disorders based on hazard analysis and critical control point (HACCP) theory.Methods:From February to July 2023, convenience sampling was used to select 76 adolescents with mood disorders and NSSI from two closed full care wards of the Affiliated Brain Hospital of Nanjing Medical University as the research subject. Adolescents were randomly divided into a control group and an experimental group. The control group received the routine diagnosis, treatment, nursing, and risk management plan, while the experimental group implemented the management plan based on the HACCP theory. This study compared the incidence of NSSI, Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSSIQ), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Accompanying Family Member Satisfaction Questionnaire scores before and after intervention between two groups of adolescents.Results:The control group included 35 patients, while the experimental group included 32 patients. After intervention, the anxiety and depression scores of the experimental group patients were lower than those of the control group, and the difference was statistically significant ( P<0.05). The incidence of NSSI in the experimental group was lower than that in the control group with a statistical difference ( P<0.05). The satisfaction of accompanying family members in the experimental group was better than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The management plan based on the HACCP theory is beneficial for reducing the occurrence of NSSI in hospitalized adolescents with mood disorders, improving their negative emotions, enhancing the satisfaction of accompanying family members, and ensuring the safety of the ward.

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 establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective:To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures.Methods:The data on platelet aggregation(n=61)and non-aggregation(n=323)of 61 donors in 2020 were collected and the causes of aggregation were analyzed.Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A(increasing the anticoagulant-to-blood ratio)and intervention group B(wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed).The collection time,average blood flow speed,number of machine alarms,anticoagulant usage,deaggregation and citrate reaction of the two groups were compared.Results:Platelet aggregation was negatively correlated with the average blood flow speed(r=-0.394)and positively correlated with the collection time(r=0.458).The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis,and the predicted accuracy was 77.1％.The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A;the collection time,number of machine alarms,anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A,all these differences were significant(P＜0.05).In the entire cohort in 2021,90.28％of the products were immediately deaggregated after collection,and 9.72％of the products were deaggregated within 4 hours.There was no statistically significant difference in deaggregation between the two intervention groups(P＞0.05).Conclusion:During apheresis platelet collection,the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation,and the intervention can be made in advance.Both intervention measures are effective in reducing platelet aggregation,however,measure B has the advantages of improving the speed of blood collection,shortening the collection time,reducing the alarm frequency and the anticoagulant usage,and reducing the incidence of citrate reaction in blood donors.

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.