BackgroundCognitive function is closely related to an individual's quality of life and social functioning， with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains， such as memory function， while its effects on other cognitive dimensions， such as executive functioning， attention， and information processing speed， remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder， thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as study participants. Subjects were randomly divided into study group （n=23） and control group （n=26） based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day， which gradually titrated upward based on individual variability， drug tolerance， and therapeutic response， with a maintenance dose ranging from 100 to 200 mg/day. In addition， the study group underwent tACS therapy for 4 weeks， with 5 sessions per week， each lasting 20 minutes. The control group received sham stimulation， in which the stimulus was interrupted after the first 30 seconds. At baseline， the 4^th week， and the 12^th week of treatment， patients were assessed using the Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， and MATRICS Consensus Cognitive Battery （MCCB）. ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups （F=260.437， 25.309， P<0.01）. At week 12 of treatment， the HAMD-17 score in the study group was lower than that in the control group （t=4.236， P<0.01）. For HAMA scores， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=248.082， 4.506， 9.500， P<0.05 or 0.01）. At weeks 4 and 12， study group reported lower HAMA scores compared with control group （t=4.580， 2.608， P<0.05 or 0.01）. Regarding the MCCB scores for attention/vigilance， verbal learning， and overall composite， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=70.331， 27.882， 51.679， 5.560， 10.948， 7.860， 8.490， 3.874， 5.025， P<0.05 or 0.01）. After intervention， the study group showed significantly higher MCCB scores for attention/vigilance， verbal learning， and overall composite at both week 4 （t=-2.149， -3.530， -2.740， P<0.05） and week 12 （t=-3.534， -3.576， -3.838， P<0.01） when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance， verbal learning， overall cognitive function， and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes， the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms， but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. ［Fund by Clinical Medical Research Transformation Special Project of Anhui Province （number， 202204295107020065）］

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Objective:To observe the changes of growth parameters and glucose and lipid metabolism indexes in GHD children treated with rhGH for 2 years, and analyze the influence of sex and age on these indexes.Methods:Clinical data of children with 80 cases GHD admitted to the Endocrine and Nutrition Clinic of the Beijing Children's Hospital affiliated to the Capital Medical University from July 2016 to December 2022 were analyzed retrospectively. All patients were treated with rhGH. The growth parameters, growth factors, glucose metabolism and lipid metabolism indexes were collected and calculated before treatment and at 3, 6, 12, 18 and 24 months after treatment, the influence of sex and age on these indexes and the correlations between these indicators and height growth rate were analyzed. Independent-sample t-test was used to compare two groups with normal distribution, one-way ANOVA was used to compare multiple groups, and repeated measures ANOVA was used to compare the mean of each time point within groups. The nonparametric rank sum test was used for the comparison of non-normal distribution measurement data. Pearson correlation analysis was used to analyze the correlation between HGV and each index.Results:A total of 80 children were enrolled, 39 boys and 41 girls. Grouped by age, there were 20 in the 3.00-5.99 age group, 41 in the 6.00-9.99 age group, and 19 in the ≥10.00 age group. All patients after 24 months of treatment had a higher height ((135.13±13.17) cm), HtSDS (-0.73 (-1.04, -0.41)), body weight (29.25 (23.13, 35.00) kg), weight standard deviation score (WtSDS) (-0.44 (-1.03, 0.03)), and body mass index (BMI) (15.99 (14.90,16.92) kg/m 2) compared to before treatment ((115.44±12.87) cm, -2.11 (-2.57, -2.03), 20.00 (16.00,25.00) kg, -1.48 (-2.12, -0.89) and 15.30 (14.45, 16.21) kg/m 2) all increased, and the differences were statistically significant (all P<0.05). The increase in HtSDS in the group aged 3.00-5.99 (1.74±0.29) was higher than that in the group aged 6.00-9.99 (1.57±0.33) and ≥10.00 (1.39±0.45), and the difference was statistically significant ( F=4.84, P=0.010). All patients showed an increase in insulin-like growth factor 1 (IGF-1) (329.50 (268.00, 417.25) μg/L) and insulin-like growth factor binding globulin 3 (IGFBP-3) (6.27 (5.50,6.95) mg/L) after 24 months of treatment compared to before treatment (131.50 (96.48,177.25) μg/L, 4.07 (3.60,4.88) mg/L), with statistical significance (all P<0.05). After treatment for 3 months, 6 months, 12 months, 18 months, and 24 months, children aged ≥ 10.00 years old with IGF-1 (353.00 (221.00, 493.00), (414.84±147.91), 441.00 (287.00, 578.00), (421.68±138.30), 376.00 (290.00, 581.00) μg/L) were higher than these in 3.00-5.99 years old group (181.00 (151.25, 237.75), (216.30±68.48), 239.50 (216.75, 325.00), (284.30±89.12), 293.00 (245.25, 343.75)) μg/L and 6.00-9.99 age group (253.00 (193.50, 345.50), (294.59±90.37), 284.00 (217.50, 377.50), (325.76±90.04), 345.00 (265.00, 431.00) μg/L, the difference was statistically significant (all P<0.05). At 3 months, 6 months, 12 months, and 18 months of treatment, IGFBP-3 levels were observed in children aged ≥ 10.00 years old (6.15 (5.52, 6.46), (6.56±1.26), (6.78±1.33), (6.78±1.38) mg/L) higher than 3.00-5.99 years old group (4.69 (4.43,5.11), (5.18±0.63), (5.61±0.84), (6.08±1.00) mg/L) and 6.00-9.99 age group (5.51 (4.76, 6.35), (5.61±0.81), (5.72±0.78), (6.03±0.80) mg/L, the difference was statistically significant (all P<0.05). All children with HbA1C (5.40 (5.20, 5.58)%), fasting blood glucose (5.06 (4.76, 5.24) mmol/L), triglycerides (0.67 (0.53, 1.02) mmol/L), TyG index (2.24±0.48), and triglyceride/HDL-C ratio (1.05 (0.73, 1.50)) after 24 months of treatment compared to before treatment (5.10 (5.00, 5.28)%, 4.78 (4.51, 5.09) mmol/L, 0.57 (0.47, 0.72) mmol/L, (1.92±0.36), 0.86 (0.65, 1.08). The level of cholesterol increased, and the total cholesterol (3.74 (3.39, 4.31) mmol/L) decreased compared to before treatment (3.95(3.64, 4.54) mmol/L), with statistical significance (all P<0.05). Female patients had higher levels of triglycerides (0.79 (0.59, 1.09) mmol/L) and TyG index (2.31±0.49) than male patients (0.66 (0.53,0.89) mmol/L, (2.16±0.46)) after 18 months of treatment. The triglyceride/HDL-C at 12 months (1.10(0.67, 1.93)), 18 months (1.16(0.83, 1.68)), and 24 months (1.26 (0.79, 1.81)) of treatment ratio was also higher than male patients (0.76 (0.61, 1.09), 0.90 (0.72, 1.08), 0.98 (0.66, 1.30)). Female HDL-C levels at 18 months (1.52 (1.29,1.75) mmol/L) and 24 months (1.45(1.29,1.76) mmol/L) of treatment were significantly lower in males (1.72 (1.45, 1.84), 1.59 (1.43, 1.92) mmol/L) with statistical significance (all P<0.05). HGV was positively correlated with IGF-1 at 12 months ( r=0.243, P=0.030) , 18 months ( r=0.277, P=0.013) and 24 months ( r=0.289, P=0.009), and it was positively correlated with IGFBP-3 at 18 months ( r=0.242, P=0.030) and 24 months ( r=0.236, P=0.035), but it was negatively correlated with HDL-C at 18 months ( r=-0.331, P=0.003) and 24 months ( r=-0.281, P=0.012). Conclusions:RhGH can obviously improve HtSDS and WtSDS in GHD children. Growth factors, glucose metabolism and lipid metabolism should be monitored during the treatment. Especially for female patients (≥10.00 years old), we should closely monitor the indexes of glucose and lipid metabolism in order to avoid metabolic diseases.

Objective:To develop a multi-parameter diagnostic model for pediatric McCune-Albright syndrome(MAS) using machine learning techniques based on laboratory data from MAS patients, with the goal of providing a rapid and reliable auxiliary diagnostic tool for clinical practice.Methods:In this retrospective study, 232 children diagnosed with MAS at the Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from March 2023 to November 2024 were enrolled as the positive group. After removing duplicate or missing data, 119 cases were finally selected for statistical analysis as the positive group. Meanwhile, 113 children with normal physical examinations during the same period were selected as the control group. The clinical manifestations of the classic " triad" in the positive group were documented. Fasting serum samples were obtained from both groups at 8: 00 AM for laboratory testing, including bone metabolism-related and hormone-related indicators, which served as candidate features. Baseline descriptive analysis was conducted on the hormone-related indicators. For the bone metabolism indicators, six machine learning models—support vector machine(SVM), XGBoost, decision tree, random forest, Logistic regression, and K-nearest neighbor(KNN)—were constructed using R software. XGBoost subgroup analysis was performed based on the triad symptoms. The contribution of individual features to model predictions was visualized using SHAP diagrams. Results:SHAP visualization indicated that age, serum phosphorus, osteocalcin, and β-C-terminal cross-linked telopeptide of type Ⅰ collagen had the greatest average impact on model predictions. Among the six models, the SVM model achieved the highest diagnostic performance, with a sensitivity of 0.742 9, a specificity of 0.909 1, and an area under the curve (AUC) of 0.917.Conclusion:This study demonstrates that machine learning models, based on data from the positive patients and normal controls, can effectively distinguish MAS patients from healthy controls. The diagnostic model developed offers clinicians a valuable tool for early detection of MAS in children, contributing to earlier diagnosis, timely intervention, and improved clinical management.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Objective:To investigate the imaging characteristics of fibrous dysplasia(FD) in children with McCune-Albright syndrome(MAS) and the correlation between FD severity and bone metabolism markers, so as to provide a basis for clinical diagnosis and treatment.Methods:A total of 46 children(38 females and 8 males) with MAS with FD who were admitted to the Department of Pediatrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2016 were included in the retrospective study, and all of them met the diagnostic criteria for either the MAS triad or dual manifestations. The extent and characteristics of FD lesions were evaluated by imaging analysis(X-ray and CT). The distribution of café-au-lait spots and endocrine abnormalities were recorded. The serum bone metabolism levels [total procollagen type 1 amino-terminal propeptide(TP1NP), osteocalcin, β-C-terminal telopeptide(β-CTX), alkaline phosphatase(ALP)], and other related indicators such as calcium, phosphorus, magnesium, and fibroblast growth factor(FGF23) levels were detected, and the association between FD severity and indicators was evaluated by Spearman correlation analysis.Results:Among the 46 children, there were 24 cases of triad(FD+ café-au-lait spots + precocious puberty) and 22 cases of dual manifestations(11 cases of FD+ café-au-lait spots or precocious puberty). The age of onset of FD patients(24 cases) with bilateral long bones and skull FD was significantly earlier than that in the unilateral FD group [(3.33±1.34)years vs(5.26±2.34)years, P<0.01], and all of them had extensive café-au-lait spots across the midline. Polyostotic FD accounted for 71.7%(33/46), mainly cystic expansive lesions involving the femur(30 cases) and tibia(24 cases), and skull FD(25 cases) mostly showed ground-glass changes; Monostotic FD(13 cases) was more common in the skull(5 cases) and phalanges(5 cases). FD severity was significantly positively correlated with ALP( ρ=0.554, P=0.002), and negatively correlated with serum phosphorus( ρ=-0.522, P=0.006). All 6 children with severe fractures had FGF23-mediated hypophosphatemia [(1.03±0.12) mmol/L vs control(1.52±0.15) mmol/L, P=0.003]. Conclusions:Extensive café-au-lait spots(across the midline) in children with MAS are strongly associated with early-onset polyostotic FD; FD severity was strongly associated with bone turnover markers(TP1NP, β-CTX, ALP) and FGF23-mediated hypophosphatemia. Early comprehensive skeletal assessment and regular FGF23 monitoring are recommended for children with MAS presenting with extensive cutaneous café-au-lait spots.

This article introduces the concept of death literacy and reviews the content,evaluation methods,target populations,reliability and validity of assessment tools for death literacy in China and abroad.It summarises the advantages and disadvantages of the tools as well as current status in application of the tools.The aim of this study is to provide a reference for researchers to select an appropriate assessment tool or to develop the assessment tools that are more suitable for the death literacy in China.

Objective To analyze the differences in the epidemiological characteristics,susceptible popula-tions,and laboratory index of patients with common acute upper respiratory tract infections(novel coronavir-us infection,influenza A and influenza B)between plateau and plain areas.Methods Clinical data of 408 008 patients with symptoms of fever or upper respiratory tract infection in the fever clinic of the Second Affiliated Hospital of Zhejiang University and General Hospital of Xizang Military Command from January 2023 to Au-gust 2024 were collected.The epidemic characteristics,susceptible populations,and peripheral blood test data were compared and analyzed.Results The total positive rate of novel coronavirus infection,influenza A virus and influenza B virus infection in plain group(17.86％)was higher than that in plateau group(14.49％),and the difference was statistically significant(P＜0.05).The positive rates(17.98％and 17.76％)of male and female upper respiratory tract infection pathogens(novel coronavirus,influenza A virus and influenza B virus)in plain group were higher than those in plateau group(13.94％and 16.00％),and the differences were statis-tically significant(P＜0.05).The total positive rates of three kinds of upper respiratory tract infection patho-gens were 16.21％,18.27％and 14.63％in the plain group,and 14.62％,14.06％and 21.26％in the plateau group,respectively.According to the results of pathogen analysis of susceptible populations,whether it was plateau or plain,the positive rate of influenza A virus was higher in the minor group,the positive rate of influ-enza B virus was highest in the adult group,and the positive rate of novel coronavirus was highest in the elder-ly group.In terms of epidemic season,plateau and plain areas were different,and the epidemic occurred earlier in the plain area.In terms of peripheral blood test indicators,there were statistically significant differences in lymphocyte count,monocyte count,neutrophil to lymphocyte ratio and other indicators between plateau group and plain group(P＜0.05),while there were no statistically significant differences in white blood cell count between plateau group and plain group(P＞0.05).Conclusion The epidemiological characteristics of acute upper respiratory tract infection in plateau area are obviously different from those in plain area,which may be related to the natural environment and human geography environment.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.