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

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.

Objective To investigate independent risk factors for unintended initial dissection of the posterior plane(UIDPP)during small incision lenticule extraction(SMILE)by surgeons with different qualifications.Methods A total of 1 600 patients(3 003 eyes)who underwent SMILE performed by three surgeons with different qualifications from April to September 2021 were selected as the research subjects,including 911 males and 689 females,with an average age of(21.82±3.55)years.The incidence of UIDPP in patients was recorded,along with a comprehensive summary of the age,gender,eyes,surgeons,surgical proficiency,subjective refraction,central corneal thickness,lenticule thickness,side cut angle,and peripheral lenticule thickness of the patients.Independent risk factors of UIDPP were analyzed using the binary logistic regression.Test level:α=0.05.Results In this study,the incidence of UIDPP was 6.56％(197/3 003),and the lenticule was successfully removed in all eyes.Multivariate logistic regression analysis demonstrated that surgeon(P=0.035),surgical proficiency(P=0.026),eyes(P=0.007),lenticule thickness(P＜0.001),and peripheral lenticule thick-ness(P＜0.001)were independent risk factors associated with the UIDPP during SMILE surgery.No significant differences were observed in other parameters(all P＞0.05).Conclusion Surgeons,surgical proficiency,eyes,lenticule thick-ness,and peripheral lenticule thickness are independent risk factors of UIDPP.

Objective:To explore the safety and efficacy of radiofrequency in the treatment of overactive bladder(OAB).Methods:A prospective, multicenter, non-randomized controlled trial was conducted. Eligible patients were divided into test group and control group in Zhejiang Provincial People’Hospital, The First Affiliated Hospital of Wenzhou Medical University, and Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from March 2019 to June 2020. Inclusion criteria: patients diagnosed with OAB, and bladder capacity>100ml. Exclusion criteria: pregnant and lactating women; patients with secondary OAB symptoms such as urinary tract obstruction; patients with uncontrolled urinary tract infection within 1 week; patients in stable stage by using other treatment methods; patients implanted with any nerve stimulator, cardiac pacemaker or implantable defibrillator; patients with malignant tumors, serious cardiovascular, cerebrovascular diseases, renal insufficiency or received BTX treatment in recent 12 months. The patients were allocated to test group and the control group in a ratio of 2∶1 according to the time sequence of the visit. The patients in the test group were treated with radiofrequency treatment. After entering the group, they were treated for 4 times at the 1st, 2nd, 7th and 8th week respectively. In the control group, the energy was turned off during the radiofrequency treatment. The patients were followed-up every week until the end of the 12th week. The treatment success rate [the average frequency of urination in 24 h was reduced more than 50% from the baseline or returned to the normal (≤8 times/day) or the average frequency of urgent urination in 24 h was reduced more than 50% from the baseline], the frequency of urination, urgent urination and nocturnal urination before and after treatment, the residual urine volume of the bladder, the quality of life (QOL) score and the occurrence of catheter related adverse events in two groups were compared.Results:114 patients were enrolled in the study, including 76 patients in the test group and 38 patients in the control group. There were no significant differences in the age [(44.2±12.8) vs. (41.7 ± 12.1) years old], male female ratio (13/63 vs. 4/34), average course of disease [2.0(1.2, 5.0) vs. 2.0 (1.0, 4.0) years], the frequency of urination[12.8 (10.6, 16.8) vs. 12.8 (10.3, 17.0) times], urgency urination [11.8(9.3, 15.8) vs. 11.8 (9.0, 17.0) times], nocturia [2.7 (1.3, 3.7) vs. 2.3(0.7, 3.3) times], residual urine volume of bladder [12.0 (3.0, 28.0) vs. 14.0 (3.7, 20.0) ml ] and the QOL score [5.0(4.0, 5.0) vs. 4.0(4.0, 5.0)]before the treatment between the two groups ( P>0.05). The treatment success rate in the test group was 76.3% (58/76), while 26.3% (10/38) in the control group, with a statistically significant difference ( P<0.01). There were significant differences between the test group and control group in the frequency of urination [9.7 (7.7, 12.0) vs. 12.9 (9.6, 15.7) times], urgent urination [7.3 (5.0, 10.0) vs. 11.7 (7.3, 15.3) times], nocturia [1.3 (0.7, 2.0) vs. 1.7 (1.0, 3.0) times] and the QOL score of the patients[3.0(1.0, 3.0) vs. 4.0(3.0, 4.5)]after the treatment(all P<0.05). The frequency of urination, urgency urination, nocturia, the residual urine volume and the QOL score in the test group were significantly improved ( P<0.05) after the treatment.The frequency of urination, nocturia, residual urine volume and the QOL score in the control group were improved ( P<0.05) after the treatment. 13 (11.4%) patients had catheter related adverse events. In the test group and the control group, there were 7 cases of macroscopic hemorrhage caused by the placement of instruments (5/76 vs. 2/38), 5 cases of acute urinary tract infection within 3 days (3/76 vs. 2/38), and 1 case of instrument breakage (catheter breakage) (0/76 vs. 1/38). There were no significant differences in the adverse events between the two groups ( P> 0.05). Conclusions:Radiofrequency treatment of OAB can effectively improve the symptoms of patients, improve the QOL of patients, and has low incidence of adverse events, with good efficacy and safety.

Objective:To explore the value of spectral CT in the preoperative evaluation of solid lung adenocarcinoma with different pathological grades based on the 2011 and 2020 version of the pathological grading system.Methods:A total of 76 cases of solid lung adenocarcinoma confirmed by surgery in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, from January 2019 to September 2021 were analyzed retrospectively. All cases were divided into groups according to the grading system for invasive adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) in 2011 and 2020 (G low group included G1 and G2 adenocarcinoma, G high group included G3 adenocarcinoma). The tumors with stage Ⅰ and Ⅱ were non-advanced and the tumors with stage Ⅲ and Ⅳ were advanced. The clinical manifestations (gender, age, smoking history and stage), routine CT parameters (tumor size, morphological characteristics, plain CT value and enhancement degree) and spectral parameters [iodine concentration, effective atomic number, enhanced monochromatic CT attenuation values of 40-200 keV (CT 40 keV-CT 200 keV), and the slope of spectral curve (k value)] were compared between G low group and G high group using independent sample t-test or Mann-Whitney U test. And the efficacy of each parameter for indicating G high adenocarcinoma was analyzed using receiver operating characteristic curve analysis and area under the curve (AUC), and the Z test was used to compare the AUC. Results:Seventy-six cases were included (59 cases of G low group and 17 cases of G high group in 2011 version; 46 cases of G low group and 30 cases of G high group in 2020 version). Among the 76 cases, 62 cases were non-advanced stage (50 cases of G low group and 12 cases of G high group in 2011 version; 37 cases of G low group and 25 cases of G high group in 2020 version) and 14 cases were advanced stage (9 cases of G low group and 5 cases in G high group in both 2011 and 2020 version). Among the non-advanced adenocarcinomas, the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase of G high group in 2011 grading system were significantly lower than those of G low group ( P<0.05), while other parameters were similar between G low and G high group in 2011 grading system ( P>0.05); and the CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase of G high group in 2020 grading system were significantly lower than those of G low group ( P<0.05). Among the advanced adenocarcinomas, all of the clinical and CT parameters were similar between G low and G high group in both 2020 and 2011 grading systems ( P>0.05). For the non-advanced adenocarcinomas, there was medium to good efficacy of the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase for diagnosing 2011 grading system G high adenocarcinoma (AUC=0.700-0.853), with CT 50 keV in venous phase as the best; while the diagnosis efficacy of CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase was poor for 2020 grading system G high adenocarcinoma (AUC=0.652-0.688), with CT 60 keV in venous phase as the best. After combining smoking history and CT 60 keV in venous phase, the diagnosis efficacy for 2020 grading system G high adenocarcinoma was slightly improved (AUC=0.772), but the difference had no significance ( Z=0.93, P=0.176). Conclusion:The spectral parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma. And the detecting efficacy for G high adenocarcinoma of IASLC 2011 version is slightly better than that of 2020 version.

Objective To investigate the association between gallstones (GS) and metabolic syndrome (MS) in southern Xinjiang, China, and to provide experience for the prevention and control of metabolic diseases in southern Xinjiang. Methods The patients with GS who visited First Division Hospital, Second Division Korla Hospital, and Third Division Hospital of Xinjiang Production and Construction Corps from March 2015 to March 2019 were enrolled as case group, and cluster sampling was used to select the individuals who underwent physical examination in Third Division 51st Regiment Hospital during the same period of time were enrolled as control group. According to inclusion and exclusion criteria, 1140 cases were enrolled in each group after 1∶ 1 matching based on age and sex. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for GS. Dummy variables were included by logistic regression to evaluate multiplicative interaction between MS components, and the parameter estimate and covariance matrix of the logistic regression model and interaction calculation table were used to calculate and evaluate additive interaction between MS components. Results The risk of GS in MS patients was 2.33 times that in non-MS patients (odds ratio [ OR ]=2.33, 95% confidence interval [ CI ]: 1.86-2.92). In addition, the components of MS also increased the risk of GS, including blood glucose ( OR =2.94, 95% CI : 2.36-3.68), blood pressure ( OR =1.50, 95% CI : 1.26-1.80), blood lipids ( OR =1.48, 95% CI : 1.25-1.75), and body mass index ( OR =1.44, 95% CI : 1.21-1.70). After adjustment for multiple factors, the risk of GS gradually increased with the increase in the number of metabolic abnormalities, i.e., one abnormality ( OR =1.55, 95% CI : 1.22-1.99), two abnormalities ( OR =2.13, 95% CI : 1.66-2.72), three abnormalities ( OR =3.48, 95% CI : 2.59-4.69), and four abnormalities ( OR =4.65, 95% CI : 2.79-7.84). No additive or multiplicative interaction was found between MS components. Conclusion GS is closely associated with MS in southern Xinjiang, and the risk of GS gradually increases with the increase in MS components. No additive or multiplicative interaction is found between GS and MS components.

Objective:To investigate the effect of astragaloside IV (AS-IV) on the secretion of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4) by high glucose injured human umbilical vein endothelial cells (HUVECs), so as to lay a foundation for further study on AS-IV improving angiogenesis by regulating SDF-1 α/CXCR4 axis of endothelial cells.Methods:HUVECs were isolated and cultured from the umbilical vein of full-term healthy newborns and identified by von Willebrand factor (vWF) combined with 4-diamino-2-phenylindole (DAPI) nuclear staining. The obtained HUVECs was cultured in EGM-2 medium with 30 mmol/L glucose for 120 h to obtain high glucose damaged HUVECs. After intervention with different concentration gradients (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L, 400 mg/L) AS-IV for 72 hours, the contents of SDF-1α and CXCR4 were detected by enzyme linked immunosorbent assay (ELISA) method to determine the best concentration of AS-IV. The supernatant of damaged HUVECs were collected at 6, 12, 24, 48 and 72 hours after intervention with the best concentration of AS-IV, and the contents of SDF-1α and CXCR4 were detected by ELISA method to determine the best action time of AS-IV. The damaged HUVECs was randomly divided into experimental group and control group, and the blank group was set up at the same time. The experimental group was treated with the best concentration of AS-IV and the best time, the control group and the blank group were treated with the same volume of phosphate buffered saline (PBS) solution, and the contents of SDF-1α and CXCR4 in each group were detected by ELISA method.Results:The vWF factor on the cell membrane was green fluorescence, and the nucleus was blue after DAPI staining. When the fusion image showed green fluorescence, HUVECs were identified by blue fluorescence. The expression of SDF-1α in damaged HUVECs was the best when treated with AS-IV of 100 mg/L for 24 hours (1 642.87 pg/ml), and the expression of CXCR4 in damaged HUVECs was the best when treated with AS-IV of 50 mg/L for 48 hours (8.44 ng/ml). Compared with the control group, the contents of SDF-1α and CXCR4 in the experimental group were significantly increased, and the difference was statistically significant ( P<0.05). While the contents of SDF-1α and CXCR4 in the experiment group were slightly less than those in the blank group and there was no statistically significant difference ( P>0.05). Conclusions:AS-IV can promote the expression of SDF-1α and CXCR4 in HUVECs damaged by high glucose to return to normal physiological level, so as to play the role of vascular repair and neovascularization.

Objective:To explore the value of dual-layer spectral detector CT in differentiating the diagnosis of lung cancer and inflammatory nodules.Methods:A total of 92 patients undergoing enhanced chest scan from March 2019 to September 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University, were retrospectively enrolled in the study. The conventional CT parameters, spectral CT parameters were measured and the nodules′ morphological characteristics were analyzed. Later the factors with statistical significance were identified as independent variables in a logistic regression model to establish models for predicting malignant nodules. ROC curve was used to assess the diagnostic performance for the conventional CT model, spectral CT parameters and combined model, respectively. Differences in the area under the ROC curve (AUC) were analyzed by the DeLong test.Results:Lobulated sign (42 and 8, respectively, χ2=10.779, P=0.001), short burr sign (41 and 7, respectively, χ2=11.911, P=0.001), pleural indentation sign (45 and 9 respectively, χ2=11.705, P=0.001), vascular convergence sign (35 and 8, respectively, χ2=5.337, P=0.021) and the venous phase iodine concentrations (IC) value [(2.1±0.5) mg/ml, (2.3±0.5) mg/ml, t=-2.464, P=0.016], normalized iodine concentrations (NIC) value (0.40±0.06, 0.45±0.08, t=-6.943, P<0.001), and Z-effective (Z eff) values (8.38±0.21, 8.49±0.19, t=-2.122, P=0.037) were significantly different between the lung cancer group and the inflammatory group, while other CT signs and CT indicators were not significantly different between the lung cancer group and the inflammatory group ( P>0.05). The conventional CT model was established with lobulated sign, short burr sign, pleural indentation sign, vascular convergence sign, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.827. The spectral CT parameter model was established with venous phase IC, venous phase NIC, and venous phase Z eff value, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.899. The conventional CT model combined spectral CT parameter model was established with the significant factors in the univariate analysis, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.925. The AUC of the combined model showed no significant difference from that of the spectral CT parameter model ( Z=1.794, P=0.073). However, AUC of the combined model was significantly higher than that of evaluation based on conventional CT alone ( Z=2.156, P=0.031). Conclusion:Spectral CT parameters combined with conventional CT signs can improve the differential diagnosis efficiency between lung cancer and inflammatory nodules.

Objective　To explore the value of diffusion weighted imaging-Alberta stroke project early CT score (DWI-ASPECTS) in predicting early neurological deterioration (END) in the patients with acute anterior circulation cerebral infarction.Methods　The data patients with acute anterior circulation cerebral infarction treated in the department of neurology of our hospital from October 01 2014 to June 30 2016 were retrospectively analyzed.According to the occurrence of END.The patients were divided into END group and non-END group.The differences of clinical variables between the two groups were analyzed and compared.ROC curve was used to evaluate the predictive value of DWI-ASPECTS score in the patients with acute anterior circulation cerebral infarction.Results　The DWI-ASPECTS score of END group was significantly lower than that of non-END group (P<0.001).The DWI-ASPECTS (95%CI 0.466~0.8,95% CI 0.466~0.8 95% score 0.009) and the LDL-C (95% CI 1.006~2.316 score 0.047) were independent risk factors for END.ROC curve shows that when the DWI-ASPECTS is 7 as the cut-off point.The area under the curve is 0.769 (95%CI 0.715~0.818),the sensitivity is 61.54% and the specificity is 88.04%.Conclusion　DWI-ASPECTS has a good predictive value in the patients with acute anterior circulation cerebral infarction.Which should be further verified by a large sample study.