Noise-induced hearing loss(NIHL)is a public health problem that requires immediate attention.Nearly one-third of hearing loss can be attributed to noise exposure.However,the molecular mechanism of NIHL is complex,and there is currently no specific drug available for preventing and treating NIHL.Therefore,it is particu-larly important to establish standardized preclinical research models of NIHL and identify molecular targets for treat-ment so as to carry out the prevention and drug treatment of NIHL effectively.In this article,we summarized the research methods and pharmacological treatment studies on NIHL to provide references for the prevention and treat-ment of NIHL.

Objective:To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients.Methods:Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization.Results:A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHEⅡscore, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHEⅡscore and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio ( OR) = 14.82, 95% confidence interval (95% CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95% CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. Conclusions:The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHEⅡscore and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

OBJECTIVE: To track analysis of viral nucleic acid test results in patients with re-positive SARS-CoV-2 infection, and provide clinical reference for nucleic acid test of re-positive cases. METHODS: A retrospective study was conducted. The multiple nucleic acid results of 96 cases with SARS-CoV-2 infection tested by medical laboratory of Shenzhen Luohu Hospital Group from January to September in 2022 were analyzed. The test dates and cycle threshold (Ct) values of detectable positive virus nucleic acid in the 96 cases were summarized and analyzed. RESULTS: A total of 96 patients with SARS-CoV-2 infection were retested re-sampled for nucleic acid testing at least 12 days after the initial positive screening. Among them, 54 cases (56.25%) had Ct value of < 35 for nucleocapsid protein gene (N) and/or open reading frame 1ab gene (ORF 1ab), 42 cases (43.75%) had Ct value ≥ 35. In the re-sampling of infected patients, N gene titers were 25.08 to 39.98 Ct cycles, and ORF 1ab gene titers were 23.16 to 39.56 Ct cycles. Compared with the positive results of the initial screening, the Ct values of N gene and/or ORF 1ab gene positive were increased in 90 cases (93.75%). Among them, the patients with the longest duration of nucleic acid positive could still be positive for double targets (the Ct value of N gene was 38.60, and the Ct value of ORF 1ab gene was 38.11) at an interval of 178 days after the initial positive screening. CONCLUSIONS Patients infected with SARS-CoV-2 can be sustained or repeatedly tested positive for nucleic acid for a long period of time, and most of them had Ct values < 35. But whether it is infectious needs to be comprehensively evaluated by combining epidemiology, variant type, samples with the alive virus, and clinical symptoms and signs.
Humans ; COVID-19 ; SARS-CoV-2 ; Retrospective Studies ; Hospital Units ; Nucleic Acids

Helicobacter pylori (HP) infection is one of the most prevalent chronic bacterial infections in the world, which is closely related to the development of gastrointestinal diseases, such as chronic gastritis, gastroduodenal ulcer and gastric cancer. Empirical treatment of HP infection may lead to antibiotic resistance, adverse reactions and poor compliance. The decreased HP eradication rate is related to antibiotic resistance, HP converting to coccoid form and admission of proton pump inhibitors (PPI). The implementation of precise therapy can effectively enhance the HP eradication rate, through antibiotics selecting based on detection of drug sensitivity phenotype and drug resistance genes, reducing adverse drug reactions, increasing patient compliance, and rationally administrating PPI, etc. This article reviews the research progress of precision therapy for HP infection to provide reference for clinicians.

Objective:To investigate the predictive value of mid-regional proadrenomedullin (MR-proADM) on poor prognosis of low-risk patients with sepsis.Methods:This was a prospective cohort study. Patients with sepsis admitted to the Emergency Intensive Care Unit of China Rehabilitation Research Center from December 2018 to December 2020 were included in this study. The patients were divided into the low-risk group (SOFA≤7) and medium-high-risk group (SOFA>7) according to the sequential organ failure assessment (SOFA) score, and the clinical characteristics of the two groups were compared. Proportional hazards regression model (COX regression model) was used to investigate the risk factors of 28-day mortality in the low-risk and medium-high-risk group. The predictive ability of MR-proADM, C-reactive protein (CRP), lactic acid (Lac), interleukin-6 (IL-6), SOFA score, and acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) score for the prognosis in each group was evaluated by receiver operating characteristic (ROC) curve. The outcomes of patients with different concentration of MR-proADM in the low-risk group were compared.Results:Totally 205 patients with sepsis were included, and the 28-day mortality was 41.0% (84/205). There were significant differences in the number of organ dysfunction, acute kidney injury, use of vasoactive drugs, Lac, IL-6, SOFA score and APACHEⅡ score between the two groups ( P<0.05). Cox regression model showed that age, MR-proADM, mechanical ventilation, IL-6 and APACHEⅡ score were the risk factors of 28-day death in the low-risk group, while MR-proADM, Lac, SOFA score and APACHEⅡ score were the risk factors of 28-day mortality in the medium-high-risk group. In each group, MR-proADM had a good predictive ability for the prognosis of patients with sepsis ( P<0.001). Especially in low-risk patients with sepsis, the predictive ability of MR-proADM was better than other indicators. Kaplan-Meier survival curve suggested that the patients with MR-proADM >2.53 nmol/L had worse prognosis than those with MR-proADM ≤2.53 nmol/L, and the difference was statistically significant ( P<0.001). In the low-risk group, the mortality of patients increased from 7.8% to 58.2% if MR-proADM >2.53 nmol/L. Conclusions:MR-proADM is a risk factor for 28-day mortality in patients with sepsis, and MR-proADM can early identify the poor prognosis of low-risk patients with sepsis.

Objective:To investigate the prognostic factors associated with unresectable (stage Ⅲa-Ⅳ, according to the 7th edition of the AJCC cancer staging manual) lung squamous cell carcinoma.Methods:We retrospectively analyzed 350 patients with inoperable locally advanced, recurrent or metastatic lung squamous cell carcinoma who were admitted to the First Affiliated Hospital of Chinese Medical University from January 2005 to June 2018. The clinical pathological data, treatment and survival follow-up information of the patients were collected. Kaplan-Meier survival was used to compare the overall survival rate of different risk groups. Univariate analysis and multivariate Cox regression analysis were used to determine the independent prognostic factors.Results:A total of 350 patients were enrolled. The median overall survival (OS) of these patients was 16.7 months. Univariate analysis showed the stage, Eastern Cooperative Oncology Group(ECOG), first-line chemotherapy evaluation (RECIST version 1.1), radiation therapy, number of systemic chemotherapy lines, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), C reactive protein (CRP), lactate dehydrogenase (LDH), whether liver, brain, boneor metastasis were associated with the OS of patients with advanced lung squamous cell carcinoma (all P<0.05). Multivariate analysis showed that ECOG score ( HR=1.855, 95% CI: 1.063-3.239, P=0.030), whether underwent lung resection ( HR=0.476, 95% CI: 0.302-0.751, P=0.001), first-line chemotherapy evaluation [stable disease (SD): HR=0.293, 95% CI: 0.159-0.540, P<0.001; complete response (CR)+ partial response (PR): HR=0.223, 95% CI: 0.120-0.413, P<0.001], CRP ( HR=1.715, 95% CI: 1.080-2.723, P=0.042), LDH ( HR=1.116, 95% CI: 0.780-1.596, P=0.002) and CEA ( HR=1.855, 95% CI: 1.361-2.528, P<0.001) before chemotherapy, liver metastasis ( HR=2.453, 95% CI: 1.461-4.120, P=0.001) are independent prognostic factors for patients with unresectable lung squamous cell carcinoma. Conclusion:The ECOG score, surgical treatment history, first-line chemotherapy, LDH, CEA and CRP before chemotherapy, liver metastasis are independent prognostic factors for patients with advanced lung squamous cell carcinoma.

Objective:To investigate the prognostic factors associated with unresectable (stage Ⅲa-Ⅳ, according to the 7th edition of the AJCC cancer staging manual) lung squamous cell carcinoma.Methods:We retrospectively analyzed 350 patients with inoperable locally advanced, recurrent or metastatic lung squamous cell carcinoma who were admitted to the First Affiliated Hospital of Chinese Medical University from January 2005 to June 2018. The clinical pathological data, treatment and survival follow-up information of the patients were collected. Kaplan-Meier survival was used to compare the overall survival rate of different risk groups. Univariate analysis and multivariate Cox regression analysis were used to determine the independent prognostic factors.Results:A total of 350 patients were enrolled. The median overall survival (OS) of these patients was 16.7 months. Univariate analysis showed the stage, Eastern Cooperative Oncology Group(ECOG), first-line chemotherapy evaluation (RECIST version 1.1), radiation therapy, number of systemic chemotherapy lines, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), C reactive protein (CRP), lactate dehydrogenase (LDH), whether liver, brain, boneor metastasis were associated with the OS of patients with advanced lung squamous cell carcinoma (all P<0.05). Multivariate analysis showed that ECOG score ( HR=1.855, 95% CI: 1.063-3.239, P=0.030), whether underwent lung resection ( HR=0.476, 95% CI: 0.302-0.751, P=0.001), first-line chemotherapy evaluation [stable disease (SD): HR=0.293, 95% CI: 0.159-0.540, P<0.001; complete response (CR)+ partial response (PR): HR=0.223, 95% CI: 0.120-0.413, P<0.001], CRP ( HR=1.715, 95% CI: 1.080-2.723, P=0.042), LDH ( HR=1.116, 95% CI: 0.780-1.596, P=0.002) and CEA ( HR=1.855, 95% CI: 1.361-2.528, P<0.001) before chemotherapy, liver metastasis ( HR=2.453, 95% CI: 1.461-4.120, P=0.001) are independent prognostic factors for patients with unresectable lung squamous cell carcinoma. Conclusion:The ECOG score, surgical treatment history, first-line chemotherapy, LDH, CEA and CRP before chemotherapy, liver metastasis are independent prognostic factors for patients with advanced lung squamous cell carcinoma.

Objective:To explore the accuracy of array comparative genomic hybridization(aCGH) in the unexpected detection of Duchenne muscular dystrophy ( DMD) gene duplication/deletion in prenatal diagnosis. Methods:A retrospective analysis was performed on 31 cases with DMD gene duplication/deletion detected by aCGH among 5 025 prenatal diagnosis samples without family history of DMD in Henan Provincial People's Hospital from July 2018 to December 2019. The multiplex ligation-dependent probe amplification (MLPA) method was used to verify the above results. The American College of Medical Genetics and Genomics (ACMG) guideline was referred for pathogenicity analysis of the detected duplicates/deletions. Descriptive analysis was adopted in analysis. Results:The total unexpected DMD gene duplication/deletion rate was 0.62% (31/5 025), among which 25 cases were with microduplication/microdeletion ≤ 200 kb and six were >200 kb; there were 24 cases of deletion, seven cases of duplication; exon or intron duplication/deletion were accounted for 19 and 12 cases, respectively. According to the five classification standards of ACMG guideline, there were 17 cases with pathogenic variants and 14 cases with uncertain pathogenicity/likely benign variants. Of the 19 with exon mutations, 17 cases were DMD intragenic variants, and two cases involved variants in and outside DMD gene, which were verified by MLPA whose results were all positive. Conclusions:The duplication/deletion of exon region of DMD gene detected by aCGH technique is accurate and reliable, which plays an important role in the diagnosis of DMD. For these cases involved both internal and external regions of DMD gene, aCGH can identify the upstream and downstream breaking points of DMD gene, thus providing the basis for ACMG grading.