Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P＜0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P＜0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P＜0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P＜0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.

Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors be-tween 2011 and 2020.Methods The protease-reverse transcriptase(PR-RT)region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020.Drug resistance mutation(DRM)rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database.Results DRM were detected in 17.2%(30/174)of samples,while transmitted drug resistance(TDR)was5.7%(10/174).Between2011 and2020,DRM and TDR rates in-creased significantly in 2019 and reached their highest levels in 2020(44.4%and 22.2%,respectively).DRM carriage was associated with people with college degree or above and with local residents(P<0.05).NNRTI DRMs were the most fre-quently detected(12.6%,22/174),followed by PIs(5.7%,10/174),with V179D/E/T and M46I being the main DRMs detected.Only one HIV-1strain(0.57%,1/174)carried a NRTI DRM(L74I).The overall rate of predicted high level re-sistance to antiretroviral drugs was 6.9%(12/174),with the highest proportion of NNRTI resistance(83.3%,10/12).Two samples were classified as highly resistant to EFV and NVP,accounting for 1.1%(2/174).CRF55_01B strains showed a significantly higher DRM rate than strains of other HIV-1 genotypes(P<0.05).Conclusion Between 2011 and 2020,the rate of HIV-1 DRMs in blood donors in Dalian showed a significant upward trend,particularly in 2019-2020,with NNRTI resistance being the most common.The combination of DRMs detection before and after implementation of ART un-der the latest national ART treatment plan would improve the effectiveness of HIV-1 prevention and control locally.

Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.

Objective To investigate the effect of aqueous extract of Scrophularia ningpoensis(AESN)on AMP-activated protein kinase(AMPK)activity in INS-1 cells under high glucose(HG)conditions.Methods INS-1 cells were cultured in HG medium and treated with different concentrations of AESN.The influences of AESN on cell viability and pyroptotic body formation were detected using the CCK-8 assay.Western blotting was used to observe the effects of AESN on AMPK expression and phosphorylation.The effect of AESN on AMPK activity was measured using time-resolved fluorescence resonance energy transfer(TR-FRET)assay.Results Compared with normal glucose controls,INS-1 cells exposed to HG showed decreased cell viabilities and increased formation of pyroptotic bubbles using CCK-8 assay.Western blotting results indicated that HG exposure led to a decrease in intracellular AMPK phosphorylation levels.However,co-incubation with AESN under HG exposure AESN treatment increased the cell viabilities and phosphorylation of AMPK and decreased the pyroptotic bubbles formation in a concentration-dependent manner.In addition,the results of TR-FRET revealed that AESN treatment effectively increased AMPK activity in a concentration-dependent manner.Conclusion AESN has an activating effect on AMPK activity in HG-treated INS-1 cells.

In recent years,the rapid advancement of biotechnology has shifted the focus of epigenetic research towards RNA modifications,which play pivotal roles across a diverse range of physiological and pathological processes,particularly in regulating the immune system.As a highly complex and precise regulatory network,the immune system involves the synergistic action of multiple im-mune cells to maintain the immune homeostasis.RNA epigenetic modification plays a crucial role in modulating the development and function of immune cells by influencing different metabolic processes of RNA.This review aims to provide a comprehensive overview of the functions and corresponding regulatory mechanisms of six RNA modifications:m6A,m1A,m5C,m7G,ac4C,and A-to-I editing in immune cells,and further explore their potential roles in complex diseases such as autoimmune diseases and tumors,in order to pro-vide new ideas and strategies for the prevention and treatment of immune-related diseases.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

With the rapid development of industry and economy,the emergence of a large number of chemicals has made of risk management more difficult.Traditional risk assessment relies on animal experiments for toxicity testing.However,animal experiments are time-consuming,costly,and unable to meet the practical needs of risk assessment.The increasing maturity of toxicity testing alternative technologies signifies the possibility of rapid,sensitive,and accurate identification of chemical toxicity.This article focuses on the research and applications of alternative toxicity testing by reviewing the background,developments,and current research at home and abroad.It also discusses the progress in alternative testing methods in such areas as cosmetics and food safety risk assessment and explores the problems with the development of alternative testing technologies and risk assessment in China.This review aims to provide a reference for the system construction of cosmetics health risk assess-ment in China.

Objective To investigate the effect of circ_0114427 on apoptosis and inflammation of alveolar epithelial cells induced by lipopolysaccharide (LPS) and its mechanism. Methods Human alveolar epithelial cells were cultured in vitro and transfected with si-circ_0114427, microRNA (miR)-330-5p mimics or co-transfected with si-circ_0114427 and anti-miR-330-5p, and the cellswere then treated with 10 mg/L LPS for 24 hours. The expression levels of circ_0114427 and miR-330-5p in the cells were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The protein levels of Cleaved-caspase3 and Cleaved-caspase9 were evaluated using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to assess the expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Cell apoptosis was analyzed using flow cytometry. The interaction between circ_0114427 and miR-330-5p was validated using a dual luciferase reporter assay. Results After LPS treatment of alveolar epithelial cells, the expression of circ_0114427 was upregulated, while miR-330-5p expression was downregulated in in the cells (P < 0.05). Knockdown of circ_0114427 or upregulation of miR-330-5p could inhibit LPS-induced apoptosis, Cleaved-caspase3, Cleaved-caspase9, IL-6, and TNF-α levels in alveolar epithelial cells (P < 0.05). Circ_0114427 directly interacted with and negatively regulated miR-330-5p. Downregulation of miR-330-5p reversed the inhibitory effect of circ_0114427 knockdown on LPS-induced cell apoptosis and inflammation. Conclusion Knockdown of circ_0114427 can inhibit LPS-induced apoptosis and inflammation in alveolar epithelial cells, possibly through upregulation of miR-330-5p.

Objective:To explore the relationship of infertility-related stress and depression of infertility women, and the effect of coping style and resilience in it.Methods:A cross sectional study was conducted in 230 infertility women who treated with Assisted Reproductive Technology in Reproductive Medical Center of the First Affiliated Hospital of Soochow University using convenience sampling method from April 2020 to April 2021 with self-made general information questionnaire, Fertility Problem Inventory, Simplified Coping Style Questionnaire, 10-item Connor-Davidson Resilience Scale and Patients' Health Questionnaire Depression Scale-9 item. And correlation and effect analysis was conducted.Results:Two hundred and nineteen questionnaires were finally collected, the effective recovery rate was 95.2%(219/230). The score of Fertility Problem Inventory was (136.21 ± 27.38) points, the score of Simplified Coping Style Questionnaire was (34.26 ± 7.66) points, the score of 10-item Connor-Davidson Resilience Scale was (27.50 ± 6.78) points, the score of Patients' Health Questionnaire Depression Scale-9 item was (4.26 ± 3.83) points. Correlation analysis results showed that infertility-related stress of infertility women was positively correlated with negative coping ( r=0.20, P<0.01) and depression ( r=0.26, P<0.01), negative coping was positively correlated with depression ( r=0.23, P<0.01). Effect analysis results showed that negative coping had a partial mediating effect between infertility-related stress and depression, and the mediating effect size was 0.05, accounting for 15.63% of the total effects. Resilience moderated the second half path of the mediation relationship ( β=-0.137, t=-2.11, P<0.05). Conclusions:The infertility-related stress is a positive predictor of depression. Negative coping has a mediating effect between infertility-related stress and depression, and resilience moderates the effect of negative coping on depression.