Objective To investigate the effects of music therapy on cognitive function and immunity of sleep-deprived mice and the potential underlying mechanisms.Methods A novel music therapy was developed by integrating elements from both Western and Chinese music.A sleep-deprived mouse model was established to explore the effects of the music combination on learning and memory of mice using Morris water maze experiments.ELISA was used to detect immune-endocrine indicators in the blood and saliva of mice and to study the effects of this music combination on IgA levels.Transcriptome high-throughput sequencing and B-cell receptor(BCR)repertoire sequencing were adopted to explore the potential mechanisms through which music therapy influenced IgA production.Results The Morris water maze test revealed that the novel music therapy could promote the recovery of cognition and memory of sleep-deprived mice.Additionally,it was found that the music combination could increase IgA levels in both blood and saliva.Transcriptome high-throughput sequencing and BCR sequencing analysis showed that the music combination enhanced the abundance of the IgA immunoglobulin light chain variable region(Igkv4-53)and heavy chain constant region(Igha).Conclusion Music therapy can help restore cognitive function and increase IgA levels in sleep-deprived mice.The mechanism may be related to the enhanced abundance of immunoglobulin light chain variable region(Igkv4-53)and heavy chain constant region(Igha).

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.

Objective:To learn about the current situation of organizational management and inter-departmental coordination and provide a basis for optimization the national joint prevention and control strategy of endemic fluorosis and arsenicosis.Methods:The staff engaged in prevention and control of endemic fluorosis and arsenicosis at the provincial, municipal, county, township, and village levels were selected as the investigation subjects. An online questionnaire survey was conducted to collect relevant information on organizational management and departmental coordination. SAS 9.4 software was used for data statistical analysis.Results:A total of 3 107 valid questionnaires were collected, covering 25 provinces, distributed in 6 regions including Northeast China, North China, East China, Central China, Northwest China, and Southwest China. Totally 92.52% (1 088/1 176) of the respondents believed that a leading group for prevention and control of endemic diseases had been established in their localities, there were statistically significant differences among different regions (χ 2 = 17.18, P = 0.004). However, the highest proportion of those who believed that no leading group had been established was in the Southwest China (14.09%, 21/149). Totally 83.97% (906/1 079) of the respondents believed that the coordination role of the leading group for endemic disease prevention and control was very good or relatively good. The proportion of survey respondents who believed that the local water resources department had a good/relatively good main responsibility in implementation of water improvement measures in drinking-water-borne fluorosis and arsenic poisoning areas, as well as in management of fluoride and arsenic reduction water improvement projects, were 90.51% (2 203/2 434) and 89.37% (2 143/2 398), respectively. The differences between different regions were statistically significant (χ 2 = 70.90, 57.40, P < 0.001). The highest proportion of general/poor cases was believed to be in the southwest region [25.14% (46/183), 24.58% (44/179)]. Totally 71.37% (187/262) of the respondents believed that the supply and distribution of low-fluorine brick tea in tea-drinking-borne endemic fluorosis areas were very good or good. Totally 90.55% (1 447/1 598) of the respondents believed that local medical insurance departments had included skeletal fluorosis patients who were covered by medical insurance. Totally 90.71% (1 474/1 625) of the respondents believed that social assistance departments had included eligible patients with skeletal fluorosis in the scope of social assistance. There were significant differences in the inclusion rate among different regions (χ 2 = 50.45, 46.22, P < 0.001). North China [18.99% (30/158), 21.43% (33/154)] and Southwest China [18.64% (33/177), 15.22% (28/184)] were the two regions with the highest percentage of respondents who believed that the above two were not included. Totally 83.19% (1 425/1 713) of the respondents believed that the local designated hospital for treatment of skeletal fluorosis had been established, there were statistically significant differences among different regions (χ 2 = 31.54, P < 0.001). North China (26.40%, 47/178) and Northwest China (24.56%, 42/171) had the highest proportion of those who believed that there were no designated treatment hospitals for skeletal fluorosis. Totally 83.58% (1 502/1 797) of the respondents believed that the utilization of medical insurance and other policy assistance was very good or good by skeletal fluorosis patients. In Northeast China (30.34%, 27/89), North China (28.41%, 50/176), Southwest China (24.00%, 48/200), and Northwest China (21.43%, 39/182), the proportion of those who believed that the utilization was average and poor were significantly lower than those in East China (11.57%, 96/180) and Central China (10.94%, 35/320, Pcorrect < 0.05). Totally 92.96% (2 747/2 955) of the respondents believed that the cooperation degree of education departments in school monitoring and health education was very good or good, and there were significant differences between different regions (χ 2 = 26.11, P < 0.001), and the highest proportion of respondents who believed that the degree of cooperation was average and poor was in Southwest China (12.63%, 37/293). Conclusions:Except for the East China and Central China, there are different degrees of problems in the organization management and/or departmental coordination and cooperation between departments of endemic fluorosis and arsenicosis prevention and control, especially in the Southwest region. All regions should raise awareness of risk prevention and control, strengthen joint prevention and control, and integrate medical and prevention mechanisms, and consolidate and improve the achievements of endemic fluorosis and arsenicosis prevention and control.

Objective:To study the relationship between microRNA (miRNA, miR)-675-3p, miR-675-5p, miR-29b-3p, miR-let-7b-3p and fluoride induced articular cartilage injury in rats.Methods:Using the factorial design, thirty 3-week-old specific pathogen free grade male Wistar rats (weighted 125 - 150 g) were selected and randomly divided into a control group, a 25 mg/L fluoride group, and a 50 mg/L fluoride group using a random number table method, with 10 rats in each group. The control group drank distilled water, while the fluoride exposure groups drank distilled water with fluoride ion concentrations of 25 and 50 mg/L, respectively. Five rats were euthanized in each group at 3 and 6 months of feeding, respectively. Visual observation was used to observe the occurrence of dental fluorosis in rats, and fluoride ion selective electrode method was used to detect the fluoride level in blood, urine, and cartilage. Hematoxylin-eosin staining and safranin O-fast green staining were used to observe the pathological changes of articular cartilage, and Mankin score was used to evaluate the grading of cartilage injury. Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage.Results:After 3 and 6 months of fluoride exposure, no dental fluorosis was observed in the control group, while rats in the 25 and 50 mg/L fluoride groups showed varying degrees of dental fluorosis. There were statistically significant differences in the levels of blood fluoride (mg/L: 0.11 ± 0.04, 0.57 ± 0.32, 0.29 ± 0.06, 0.07 ± 0.01, 0.31 ± 0.05, 0.38 ± 0.06), urine fluoride (mg/L: 1.81 ± 0.58, 13.18 ± 2.29, 66.11 ± 20.74, 2.35 ± 1.08, 14.79 ± 3.87, 28.32 ± 4.79), and cartilage fluoride (mg/kg: 341.83 ± 44.07, 612.99 ± 174.72, 991.26 ± 227.32, 338.29 ± 72.53, 957.09 ± 195.86, 1 535.53 ± 89.01) among in rats the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group ( F = 7.76, 42.78, 40.54, 23.10, 18.96, 80.81, P < 0.05). In the 50 mg/L fluoride group, there were statistically significant differences in the levels of urine fluoride and cartilage fluoride of rats exposed for different times ( t = 4.45, - 3.80, P < 0.05). The Mankin score grading for cartilage injury showed that at 3 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 4, and 1 rats with mild injury, and 0, 1, and 4 rats with moderate injury, respectively. At 6 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 3, and 0 rats with mild injury, 0, 1, and 3 rats with moderate injury, and 0, 1, and 2 rats with severe injury, respectively. Real-time fluorescence quantitative PCR results showed that fluoride exposure dose had individual effects on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 8.68, 7.97, 9.34, 10.14, P < 0.05). There was no individual effect of fluoride exposure time on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 0.00, 0.15, 0.63, 0.53, P > 0.05). However, there was no interaction effect between fluoride exposure time and dose on the above-mentioned miRNA ( F = 0.68, 0.05, 0.22, 0.24, P > 0.05). The correlation analysis results showed that miR-675-3p and miR-675-5p in cartilage were negatively correlated with blood fluoride, urine fluoride, and cartilage fluoride ( r = - 0.37, - 0.42, - 0.56, - 0.53, - 0.57, - 0.53, P < 0.05), while miR-29b-3p and miR-let-7b-3p were positively correlated with urine fluoride and cartilage fluoride ( r = 0.58, 0.40, 0.48, 0.47, P < 0.05). The results of ordered logistic regression analysis showed that miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p were influencing factors of dental fluorosis grading ( OR = 0.13, 0.04, 1.55, 2.58, P < 0.05) and Mankin score grading ( OR = 0.04, 0.06, 1.41, 1.58, P < 0.05). Conclusion:MiR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p may be involved in the process of fluoride induced articular cartilage injury.

Objective:To study the relationship between microRNA (miRNA, miR)-675-3p, miR-675-5p, miR-29b-3p, miR-let-7b-3p and fluoride induced articular cartilage injury in rats.Methods:Using the factorial design, thirty 3-week-old specific pathogen free grade male Wistar rats (weighted 125 - 150 g) were selected and randomly divided into a control group, a 25 mg/L fluoride group, and a 50 mg/L fluoride group using a random number table method, with 10 rats in each group. The control group drank distilled water, while the fluoride exposure groups drank distilled water with fluoride ion concentrations of 25 and 50 mg/L, respectively. Five rats were euthanized in each group at 3 and 6 months of feeding, respectively. Visual observation was used to observe the occurrence of dental fluorosis in rats, and fluoride ion selective electrode method was used to detect the fluoride level in blood, urine, and cartilage. Hematoxylin-eosin staining and safranin O-fast green staining were used to observe the pathological changes of articular cartilage, and Mankin score was used to evaluate the grading of cartilage injury. Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage.Results:After 3 and 6 months of fluoride exposure, no dental fluorosis was observed in the control group, while rats in the 25 and 50 mg/L fluoride groups showed varying degrees of dental fluorosis. There were statistically significant differences in the levels of blood fluoride (mg/L: 0.11 ± 0.04, 0.57 ± 0.32, 0.29 ± 0.06, 0.07 ± 0.01, 0.31 ± 0.05, 0.38 ± 0.06), urine fluoride (mg/L: 1.81 ± 0.58, 13.18 ± 2.29, 66.11 ± 20.74, 2.35 ± 1.08, 14.79 ± 3.87, 28.32 ± 4.79), and cartilage fluoride (mg/kg: 341.83 ± 44.07, 612.99 ± 174.72, 991.26 ± 227.32, 338.29 ± 72.53, 957.09 ± 195.86, 1 535.53 ± 89.01) among in rats the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group ( F = 7.76, 42.78, 40.54, 23.10, 18.96, 80.81, P < 0.05). In the 50 mg/L fluoride group, there were statistically significant differences in the levels of urine fluoride and cartilage fluoride of rats exposed for different times ( t = 4.45, - 3.80, P < 0.05). The Mankin score grading for cartilage injury showed that at 3 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 4, and 1 rats with mild injury, and 0, 1, and 4 rats with moderate injury, respectively. At 6 months of fluoride exposure, there were 4, 0, and 0 rats with normal cartilage in the control group, 25 mg/L fluoride group, and 50 mg/L fluoride group, 1, 3, and 0 rats with mild injury, 0, 1, and 3 rats with moderate injury, and 0, 1, and 2 rats with severe injury, respectively. Real-time fluorescence quantitative PCR results showed that fluoride exposure dose had individual effects on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 8.68, 7.97, 9.34, 10.14, P < 0.05). There was no individual effect of fluoride exposure time on the expression of miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p in cartilage ( F = 0.00, 0.15, 0.63, 0.53, P > 0.05). However, there was no interaction effect between fluoride exposure time and dose on the above-mentioned miRNA ( F = 0.68, 0.05, 0.22, 0.24, P > 0.05). The correlation analysis results showed that miR-675-3p and miR-675-5p in cartilage were negatively correlated with blood fluoride, urine fluoride, and cartilage fluoride ( r = - 0.37, - 0.42, - 0.56, - 0.53, - 0.57, - 0.53, P < 0.05), while miR-29b-3p and miR-let-7b-3p were positively correlated with urine fluoride and cartilage fluoride ( r = 0.58, 0.40, 0.48, 0.47, P < 0.05). The results of ordered logistic regression analysis showed that miR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p were influencing factors of dental fluorosis grading ( OR = 0.13, 0.04, 1.55, 2.58, P < 0.05) and Mankin score grading ( OR = 0.04, 0.06, 1.41, 1.58, P < 0.05). Conclusion:MiR-675-3p, miR-675-5p, miR-29b-3p, and miR-let-7b-3p may be involved in the process of fluoride induced articular cartilage injury.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.

Objective:To learn about the current situation of organizational management and inter-departmental coordination and provide a basis for optimization the national joint prevention and control strategy of endemic fluorosis and arsenicosis.Methods:The staff engaged in prevention and control of endemic fluorosis and arsenicosis at the provincial, municipal, county, township, and village levels were selected as the investigation subjects. An online questionnaire survey was conducted to collect relevant information on organizational management and departmental coordination. SAS 9.4 software was used for data statistical analysis.Results:A total of 3 107 valid questionnaires were collected, covering 25 provinces, distributed in 6 regions including Northeast China, North China, East China, Central China, Northwest China, and Southwest China. Totally 92.52% (1 088/1 176) of the respondents believed that a leading group for prevention and control of endemic diseases had been established in their localities, there were statistically significant differences among different regions (χ 2 = 17.18, P = 0.004). However, the highest proportion of those who believed that no leading group had been established was in the Southwest China (14.09%, 21/149). Totally 83.97% (906/1 079) of the respondents believed that the coordination role of the leading group for endemic disease prevention and control was very good or relatively good. The proportion of survey respondents who believed that the local water resources department had a good/relatively good main responsibility in implementation of water improvement measures in drinking-water-borne fluorosis and arsenic poisoning areas, as well as in management of fluoride and arsenic reduction water improvement projects, were 90.51% (2 203/2 434) and 89.37% (2 143/2 398), respectively. The differences between different regions were statistically significant (χ 2 = 70.90, 57.40, P < 0.001). The highest proportion of general/poor cases was believed to be in the southwest region [25.14% (46/183), 24.58% (44/179)]. Totally 71.37% (187/262) of the respondents believed that the supply and distribution of low-fluorine brick tea in tea-drinking-borne endemic fluorosis areas were very good or good. Totally 90.55% (1 447/1 598) of the respondents believed that local medical insurance departments had included skeletal fluorosis patients who were covered by medical insurance. Totally 90.71% (1 474/1 625) of the respondents believed that social assistance departments had included eligible patients with skeletal fluorosis in the scope of social assistance. There were significant differences in the inclusion rate among different regions (χ 2 = 50.45, 46.22, P < 0.001). North China [18.99% (30/158), 21.43% (33/154)] and Southwest China [18.64% (33/177), 15.22% (28/184)] were the two regions with the highest percentage of respondents who believed that the above two were not included. Totally 83.19% (1 425/1 713) of the respondents believed that the local designated hospital for treatment of skeletal fluorosis had been established, there were statistically significant differences among different regions (χ 2 = 31.54, P < 0.001). North China (26.40%, 47/178) and Northwest China (24.56%, 42/171) had the highest proportion of those who believed that there were no designated treatment hospitals for skeletal fluorosis. Totally 83.58% (1 502/1 797) of the respondents believed that the utilization of medical insurance and other policy assistance was very good or good by skeletal fluorosis patients. In Northeast China (30.34%, 27/89), North China (28.41%, 50/176), Southwest China (24.00%, 48/200), and Northwest China (21.43%, 39/182), the proportion of those who believed that the utilization was average and poor were significantly lower than those in East China (11.57%, 96/180) and Central China (10.94%, 35/320, Pcorrect < 0.05). Totally 92.96% (2 747/2 955) of the respondents believed that the cooperation degree of education departments in school monitoring and health education was very good or good, and there were significant differences between different regions (χ 2 = 26.11, P < 0.001), and the highest proportion of respondents who believed that the degree of cooperation was average and poor was in Southwest China (12.63%, 37/293). Conclusions:Except for the East China and Central China, there are different degrees of problems in the organization management and/or departmental coordination and cooperation between departments of endemic fluorosis and arsenicosis prevention and control, especially in the Southwest region. All regions should raise awareness of risk prevention and control, strengthen joint prevention and control, and integrate medical and prevention mechanisms, and consolidate and improve the achievements of endemic fluorosis and arsenicosis prevention and control.

Objective:To investigate the levels of microRNA (miR) -106b-5p and miR-760 in the serum of early lung cancer patients, and the clinical value of the combination of them and low-dose spiral CT in the diagnosis of early lung cancer.Methods:Ninety early lung cancer patients (lung cancer group) who underwent treatment in Cangzhou People's Hospital of Hebei Province from January 2022 to March 2023 were collected as research subjects, meantime, 90 patients with benign pulmonary lesions (benign pulmonary nodules) diagnosed by pathology were selected as the control group. The levels of miR-106b-5p and miR-760 in the serum of two groups were compared, the results of low-dose spiral CT examination were analyzed; receiver operating characteristic curve was drawn to determine the optimal cut-off values of serum miR-106b-5p and miR-760; four grid table method was applied to analyze the diagnostic efficacy of serum miR-106b-5p, miR-760 combined with low-dose spiral CT for early lung cancer.Results:The level of miR-106b-5p in lung cancer group was higher than that in control group (1.39±0.31 vs. 1.04±0.30), serum miR-760 level was lower than that in control group (0.75±0.24 vs. 1.02±0.26), with statistically significant differences ( t=7.70, P<0.001; t=7.24, P<0.001). The area under curve (AUC) of miR-106b-5p, miR-760 and low-dose spiral CT in the diagnosis of early lung cancer was 0.83, 0.81 and 0.82, the accuracy was 76.67%, 77.22% and 81.67%, the sensitivity was 84.44%, 81.11% and 76.67%, and the specificity was 68.89%, 73.33% and 86.67%, respectively. The AUC, accuracy, sensitivity, and specificity of serum miR-106b-5p, miR-760 combined with low-dose spiral CT in diagnosing early lung cancer were 0.96, 90.00%, 94.44%, and 85.56%, respectively. The accuracy of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=11.52, P=0.001; χ2=10.72, P=0.001; χ2=5.14, P=0.023), the sensitivity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=4.77, P=0.029; χ2=7.46, P=0.006; χ2=11.51, P=0.001), the specificity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 ( χ2=7.11, P=0.008; χ2=4.12, P=0.042) . Conclusion:The serum level of miR-106b-5p is significantly increased in early lung cancer patients, while the serum level of miR-760 is significantly reduced. The combination of miR-106b-5p, miR-760 and low-dose spiral CT has high diagnostic value for early lung cancer.

Objective To explore the effect and potential mechanisms of melatonin combined with gemcitabine on the chemosensitivity of human pancreatic cancer cell line PANC-1.Methods Human pancreatic cancer cell line PANC-1 was trea-ted with gemcitabine alone or in combination with melatonin.Cell viability was assessed using CCK-8.Effect of melatonin and gem-citabine alone or in combination on the clonogenic capacity of PANC-1 cells were observed through colony formation experiments.Scratch assays and transwell experiments were conducted to evaluate cell migration ability.Reactive oxygen species(ROS)and mitochondrial membrane point JC-1 assay kit were used to determine reactive oxygen species synthesis and membrane potential levels.Intracellular Fe2+level was measured using ferrous ion fluorescent probe.The protein expression levels of LC3,P62,GPX4 and SLC7A11 in different treatment groups were detected by immunofluorescence and Western blotting.Results CCK-8 results showed that the viability of PANC-1 cells was inhibited by gemcitabine alone after 48 h and 72 h of treatment in a time-and dose-dependent manner.The cell viability of gemcitabine combined with melatonin group was significantly lower than that of gemcitabine group,and the cell viability decreased with the increase of melatonin concentration.Scratch assays,transwell experiments,and plate colony formation assay results demonstrated that the proliferation and migration of cells in the gemcitabine combined with the me-latonin group were significantly inhibited compared with the gemcitabine group.The levels of reactive oxygen species and Fe2+in PANC-1 in gemcitabine combined with the melatonin group were higher than those in the gemcitabine group,and the mitochondri-al membrane potential was significantly decreased(P＜0.01).Western blotting and immunofluorescence results showed that the ra-tio of autophagy-related protein LC3-Ⅱ/LC3-Ⅰ in gemcitabine combined with the melatonin group was lower than that in the gem-citabine group,and the expression of P62 was up-regulated,and the expression of anti-iron death-related protein GPX4 and SLC7A11 was significantly inhibited(P＜0.05),suggesting that melatonin combined with gemcitabine can inhibit autophagy and promote ferroptosis in PANC-1 cells.Conclusion Melatonin enhances the chemosensitivity of pancreatic cancer cell PANC-1 to gemcitabine by inhibiting autophagy and promoting ferroptosis of tumor cells.