Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

Objective To investigate the differences in speech recognition in noise between patients with con-genital and acquired single-sided deafness.Methods Sixty-two patients with single-sided deafness were included in this study,which included 31 congenital single-sided deafness(CSSD)cases and 31 acquired single-sided deafness(ASSD)cases according to the onset of deafness.Thirty-one normal hearing(NH)subjects were also included in this study as the control group.The ability of speech recognition in noise were tested and compared among the three groups,meanwhile the differences between patients with left and right single-sided deafness were compared.Results The speech recognition threshold in noise of ASSD patients was significantly higher than that of CSSD patients,and both of them were significantly higher than that of the NH subjects.Under the 0 and-2 dB signal-to-noise ra-tio conditions,the speech recognition score was significantly lower in ASSD patients compared to CSSD patients,but only in ASSD patients it was significantly lower than that of the NH group,with no significant difference be-tween CSSD patients and the NH group.A significant difference in speech recognition thresholds was observed be-tween left and right CSSD patients.Conclusion CSSD have better speech recognition in noise than ASSD patients,suggesting better central function compensation.In addition,the side of deafness affects the speech recognition per-formance of CSSD patients.

Psoriasis is a chronic inflammatory skin disease with worldwide prevalence,primarily characterized by epidermal hyperplasia,abnormal keratinization,and immune cell infiltration,with a significant negative impact on patients' quality of life and mental well-being.The onset of psoriasis is closely associated with genetic susceptibility,immune dysregulation,and environmental factors.Despite research progress into the pathogenesis of psoriasis,existing treatment method still face problems including limited efficacy and obvious side effects.There is thus an urgent need for an in-depth analysis of its pathological network and the development of novel interventional strategies.The imiquimod-induced psoriasis animal model has accordingly become a crucial tool for studying psoriasis owing to its high reproducibility and excellent pathological simulation.This review systematically summarizes the core mechanism of action of the imiquimod-induced psoriasis model,expounds on the molecular basis of its action via pathways such as the cascade reaction of the core immune-inflammatory axis,the multi-regulatory network of downstream synergistic mechanisms,and the interaction between host and environmental factors.Research based on this model has successfully verified the therapeutic effects of various targeted therapies and natural products on psoriasis,demonstrating its important application value in therapeutic interventional research.We also discuss the limitations of the imiquimod-induced psoriasis model,and indicate future research directions,with the aim of providing references for further in-depth research and the treatment of psoriasis.

Objective To investigate the differences in speech recognition in noise between patients with con-genital and acquired single-sided deafness.Methods Sixty-two patients with single-sided deafness were included in this study,which included 31 congenital single-sided deafness(CSSD)cases and 31 acquired single-sided deafness(ASSD)cases according to the onset of deafness.Thirty-one normal hearing(NH)subjects were also included in this study as the control group.The ability of speech recognition in noise were tested and compared among the three groups,meanwhile the differences between patients with left and right single-sided deafness were compared.Results The speech recognition threshold in noise of ASSD patients was significantly higher than that of CSSD patients,and both of them were significantly higher than that of the NH subjects.Under the 0 and-2 dB signal-to-noise ra-tio conditions,the speech recognition score was significantly lower in ASSD patients compared to CSSD patients,but only in ASSD patients it was significantly lower than that of the NH group,with no significant difference be-tween CSSD patients and the NH group.A significant difference in speech recognition thresholds was observed be-tween left and right CSSD patients.Conclusion CSSD have better speech recognition in noise than ASSD patients,suggesting better central function compensation.In addition,the side of deafness affects the speech recognition per-formance of CSSD patients.

Psoriasis is a chronic inflammatory skin disease with worldwide prevalence,primarily characterized by epidermal hyperplasia,abnormal keratinization,and immune cell infiltration,with a significant negative impact on patients' quality of life and mental well-being.The onset of psoriasis is closely associated with genetic susceptibility,immune dysregulation,and environmental factors.Despite research progress into the pathogenesis of psoriasis,existing treatment method still face problems including limited efficacy and obvious side effects.There is thus an urgent need for an in-depth analysis of its pathological network and the development of novel interventional strategies.The imiquimod-induced psoriasis animal model has accordingly become a crucial tool for studying psoriasis owing to its high reproducibility and excellent pathological simulation.This review systematically summarizes the core mechanism of action of the imiquimod-induced psoriasis model,expounds on the molecular basis of its action via pathways such as the cascade reaction of the core immune-inflammatory axis,the multi-regulatory network of downstream synergistic mechanisms,and the interaction between host and environmental factors.Research based on this model has successfully verified the therapeutic effects of various targeted therapies and natural products on psoriasis,demonstrating its important application value in therapeutic interventional research.We also discuss the limitations of the imiquimod-induced psoriasis model,and indicate future research directions,with the aim of providing references for further in-depth research and the treatment of psoriasis.

Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

Objectives:To examine the proportion and trends of cervical adenocarcinoma in cervical cancer (ICC), mainly including cervical adenocarcinoma (CADC) and squamous cervical cancer (SCC) in China, and to analyze the distribution of human papilloma virus (HPV) in CADC and SCC.Methods:Published studies reporting HPVs distribution in various histological types or relative proportions of CADC in ICC in China were identified manually and searched systematically in Medline, Embase, Cochrane Library databases, CNKI and Wanfang since the databases were established until October 2022. Meta-analysis was performed using Stata 16.0 software. And we applied the random-effects models to estimate the combined effect values due to the high heterogeneity.Results:Twenty-three studies were eligible. The relative prevalence of CADC was 9.0% (95% CI, 7.7%－10.3%). According to the diagnosis time of ICC, the patients were divided into three time periods, which is 1979-2005, 2006-2011, 2012-2022 respectively. The prevalence of CADC by time was: 6.0% in 1979-2005, 8.1% in 2006-2011, and 9.5% in 2012-2022, respectively, with no statistically significant trend in proportions over time (χ 2=5.03, P=0.081). Meanwhile, the percentage of CADC also varies by regions, and the highest percentage of CADC was found in the eastern region (11.2%), followed by the western region (7.3%) and the central region (5.9%). The total prevalence of HPV infection in CADC was 72.3%, which was lower than 92.0% in SCC, and the difference was statistically significant (χ 2=300.89, P＜0.01). To be specific, the top three HPV types prevalent in CADC were HPV18 (45.0%), HPV16 (22.0%), and HPV52 (7.3%), and those prevalent in the SCC were HPV16 (64.2%), HPV52 (5.6%), HPV18 (5.4%). The results of the Egger's test, and Begg's test showed that there was no publication bias in this study and sensitivity analysis showed that the results of this study were fairly stable. Conclusions:The proportion of CADC in China has increased in a limited way in the past decades, and there are regional differences in the proportion of CADC. The predominant type is HPV18 in CADC and HPV16 in SCC. To eliminate the limitations of the secondary literature, a multicenter study with consistent diagnostic levels and identical HPV genotyping tests is still needed in the future to better characterize the relative proportion of cervical adenocarcinoma and the trend of HPV changes, which will provide a basis for the improvement of HPV vaccine and screening policies.

Objectives:To examine the proportion and trends of cervical adenocarcinoma in cervical cancer (ICC), mainly including cervical adenocarcinoma (CADC) and squamous cervical cancer (SCC) in China, and to analyze the distribution of human papilloma virus (HPV) in CADC and SCC.Methods:Published studies reporting HPVs distribution in various histological types or relative proportions of CADC in ICC in China were identified manually and searched systematically in Medline, Embase, Cochrane Library databases, CNKI and Wanfang since the databases were established until October 2022. Meta-analysis was performed using Stata 16.0 software. And we applied the random-effects models to estimate the combined effect values due to the high heterogeneity.Results:Twenty-three studies were eligible. The relative prevalence of CADC was 9.0% (95% CI, 7.7%－10.3%). According to the diagnosis time of ICC, the patients were divided into three time periods, which is 1979-2005, 2006-2011, 2012-2022 respectively. The prevalence of CADC by time was: 6.0% in 1979-2005, 8.1% in 2006-2011, and 9.5% in 2012-2022, respectively, with no statistically significant trend in proportions over time (χ 2=5.03, P=0.081). Meanwhile, the percentage of CADC also varies by regions, and the highest percentage of CADC was found in the eastern region (11.2%), followed by the western region (7.3%) and the central region (5.9%). The total prevalence of HPV infection in CADC was 72.3%, which was lower than 92.0% in SCC, and the difference was statistically significant (χ 2=300.89, P＜0.01). To be specific, the top three HPV types prevalent in CADC were HPV18 (45.0%), HPV16 (22.0%), and HPV52 (7.3%), and those prevalent in the SCC were HPV16 (64.2%), HPV52 (5.6%), HPV18 (5.4%). The results of the Egger's test, and Begg's test showed that there was no publication bias in this study and sensitivity analysis showed that the results of this study were fairly stable. Conclusions:The proportion of CADC in China has increased in a limited way in the past decades, and there are regional differences in the proportion of CADC. The predominant type is HPV18 in CADC and HPV16 in SCC. To eliminate the limitations of the secondary literature, a multicenter study with consistent diagnostic levels and identical HPV genotyping tests is still needed in the future to better characterize the relative proportion of cervical adenocarcinoma and the trend of HPV changes, which will provide a basis for the improvement of HPV vaccine and screening policies.

ObjectiveTo investigate the therapeutic effect of ganoderic acid A （GA-A） on a mouse model of concanavalin A （ConA）-induced autoimmune hepatitis （AIH）. MethodsA total of 35 mice were randomly divided into control group （NC group）， model group （ConA group）， and low-， middle-， and high-dose GA-A treatment groups （GA-A-L， GA-A-M， and GA-A-H groups， respectively）， with 7 mice in each group. ConA was injected via the caudal vein of mice to establish a classic mouse model of AIH， and different doses of GA-A were administered via intraperitoneal injection 1 hour later for treatment. Proteomic techniques were used to investigate the protective mechanism of GA-A on hepatocytes， and HL-60 cells were differentiated into dHL-60 neutrophils by all-trans retinoic acid in vitro to validate the mechanism of action of GA-A. Related indicators were measured， including inflammatory markers （the activities of serum alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］， HE staining， and inflammation-related genes）， apoptosis markers （TUNEL staining）， neutrophils， and neutrophil extracellular trap （NET） markers （myeloperoxidase ［MPO］， citrullinated histone H3 ［CitH3］， Ly6G， and free double-stranded DNA ［dsDNA］）， and p38 phosphorylation markers. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the NC group， the ConA group had significant increases in the serum levels of ALT and AST （both P<0.001）， and compared with the ConA group， GA-A treatment significantly reduced the levels of ALT and AST （both P<0.01）. HE staining showed that the mice in the ConA group had significant liver necrosis， while GA-A treatment significantly reduced the area of liver necrosis and the number of TUNEL-positive cells （both P<0.05）. Compared with the ConA group， the GA-A group had significant reductions in the expression levels of the inflammatory factors interleukin-6， tumor necrosis factor-α， and interferon gamma in serum and liver tissue （all P<0.05）. The proteomic analysis showed that GA-A alleviated ConA-induced acute immune liver injury by inhibiting the release of NET and the p38 MAPK pathway. Immunofluorescent staining of mouse liver tissue showed that compared with the ConA group， the GA-A group had significant reductions in the number of MPO-positive neutrophils and the number of cells with positive Ly6G and CitH3 （all P<0.01）. Western Blot and dsDNA testing showed that GA-A significantly inhibited the levels of the NET markers dsDNA and CitH3 and the level of p38 phosphorylation in liver tissue and dHL-60 cells （all P<0.05）. ConclusionGA-A alleviates liver inflammatory response and hepatocyte death by inhibiting the p38 MAPK pathway and the release of NET， thereby alleviating ConA-induced acute immune liver injury. This study provides a theoretical basis for the use of GA-A to treat immune liver injury by regulating neutrophil function.

Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME.