Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

ObjectiveTo investigate the mechanism underlying the effects of three formulas of the method of warming Yang and relieving depression on anxiety- and depression-like behaviors in the mice subjected to a two-hit paradigm of maternal separation （MS） combined with restraint stress （RS）. MethodsNeonatal mice were randomly assigned into the following groups： Blank control， MS alone， model （MS+RS）， warming Yang （WY，5.85 g·kg^-1）， relieving depression （RD，12.03 g·kg^-1）， warming Yang and relieving depression （WYRD，16.71 g·kg^-1）， and fluoxetine groups （2.6 mg·kg^-1）. MS was conducted on postnatal day 5 （PD5）. Weaning and preventive drug administration were carried out on PD21， and restraint stress was applied on PD90. Anxiety- and depression-like behaviors were assessed using the open field test （OFT）， the elevated zero maze test and tail suspension test （TST）. High-performance liquid chromatography with electrochemical detection （HPLC-ECD） was employed to measure the levels of neurotransmitters， including 5-hydroxytryptamine （5-HT） and dopamine （DA）， in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of 5-HT_1A receptor （5-HT_1AR）， serotonin transporter （SERT）， monoamine oxidase A （MAOA）， glucocorticoid receptor （GR）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing hormone （CRH）， brain-derived neurotrophic factor （BDNF）， and tyrosine kinase receptor B （TrkB）. Immunohistochemistry （IHC） was applied to assess the protein expression levels of 5-HT_1AR， 5-HT_2A receptor （5-HT_2AR）， 5-HT_2C receptor （5-HT_2CR）， GR， and CRH receptor 1 （CRHR1）. The protein expression levels of BDNF and TrkB in the hippocampus were measured using the fully automated protein expression analysis system （Simple Wes）. ResultsIn the behavioral tests， compared with the blank control group， the model group exhibited significant increases in locomotor distance and central area crossings （P<0.05， P<0.01）in OFT， as well as a significant increase in immobility time in the TST （P<0.05）. Compared with the model group， the RD， WYRD， and fluoxetine groups all showed significantly reduced central area crossings （P<0.05， P<0.01）. Regarding neurotransmitter levels， compared with the blank control group， the model group had significantly decreased hippocampal epinephrine （E） and dopamine （DA） content （P<0.05， P<0.01）. Compared with the MS group， the model group showed significant decreases in hippocampal norepinephrine （NE）， E， and 5-HT content （P<0.05， P<0.01）. Compared with the model group， the WY group decreased hippocampal NE， DA， and 5-HT content （P<0.01）， while the RD， WYRD， and fluoxetine groups exhibited significantly increased hippocampal E content （P<0.01）. At the molecular level， compared with the blank control and MS groups， the model group showed significant increases in mRNA levels of 5-HT_1AR， SERT， MAOA， ACTH， and CRH （P<0.01）， and significant decreases in mRNA levels of tryptophan hydroxylase （TPH）， GR， BDNF， and TrkB （P<0.01）. Protein expression of 5-HT_1AR， 5-HT_2AR， and 5-HT_2CR was also significantly elevated （P<0.05， P<0.01） in the model group. Compared with the model group， the RD group showed significant decreases in SERT， MAOA， and CRH mRNA （P<0.05， P<0.01）， significant increases in TPH， BDNF， and TrkB mRNA （P<0.01）， significantly reduced protein expression of 5-HT_1AR， 5-HT_2AR， and 5-HT_2CR （P<0.05）， and significantly increased GR protein expression. The WY group showed a significant increase in ACTH mRNA expression （P<0.01）. The fluoxetine group exhibited significant decreases in MAOA and CRH mRNA （P<0.05， P<0.01）， significant increases in TPH， BDNF， and TrkB mRNA （P<0.01）， significantly reduced 5-HT_2AR protein expression （P<0.01）， and significantly increased GR protein expression（P<0.05）. ConclusionThe method of warming Yang and relieving depression can ameliorate anxiety- and depression-like behaviors in two-hit mice. Its mechanism may be associated with the BDNF/TrkB signaling pathway， as well as the HPA axis and serotonergic system.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth， the rats were randomly divided into blank （NC） group， maternal-infant separation （MS） group， restraint stress （RS） group， maternal-infant separation combined with restraint stress （MRS） group， Wenyang group， Jieyu group， Wenyang Jieyu （XSF） group， and minocycline group. Maternal-infant separation was performed on day 5 （PD5）， followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group， Xiaoyao group， XSF group and minocycline group were 5.85， 12.03， 16.71 g·kg^-1 and 50 mg·kg^-1， respectively. Restraint stress was applied on PD90. The model was evaluated using glucose， social interaction， open field， and O-maze behavior tests， as well as high-performance liquid chromatography to measure serotonin， dopamine， and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 （Iba-1） protein， a marker of hippocampal microglia， was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of M1 markers， JAK2/STAT3 pathway-related genes， and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group， the MRS group exhibited depression-like behavior， with significantly decreased levels of neurotransmitters in the hippocampus （P<0.05， P<0.01）， increased expression of Iba-1 （P<0.01）， and elevated protein levels of JAK2 and STAT3 （P<0.05）. The mRNA expression levels of CD68， CD11b， IL-1β， JAK2， and STAT3 were significantly increased （P<0.01）， while IL-10 mRNA expression was significantly decreased （P<0.01）. Compared with the MRS group， the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups， the hippocampal neurotransmitter content was significantly increased （P<0.05， P<0.01）， and Iba-1 expression was significantly decreased （P<0.01）. The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68， CD11b， JAK2， STAT3， and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups （P<0.05， P<0.01）， while IL-10 mRNA expression was significantly increased （P<0.05， P<0.01）. ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.

Objective:To perform routine plasma test, SARS-CoV-2 nucleic acid test, and respiratory pathogenic microorganism nucleic acid test on plasma samples collected from 1 040 healthy plasma donors in winter.Methods:Plasma samples were collected from 1 040 healthy plasma donors at Yunmeng Plasma Collection Station in the winter of 2020. Routine plasma test, HBV/HCV/HIV nucleic acid test, SARS-CoV-2 nucleic acid test, and 22 respiratory pathogenic microorganism nucleic acid test were performed to analyze the quality of blood plasmas.Results:All plasma samples were qualified in the routine tests, meeting the requirements of the Chinese Pharmacopoeia, and tested negative for SARS-CoV-2 nucleic acid. Respiratory pathogenic microorganism nucleic acids were detected in 29 samples with a positive rate of 2.79% (29/1 040). There were 21 cases of simple virus infections, including 17 cases of coronavirus subtype infection, three cases of parainfluenza virus type 2 infection, and one case of human bocavirus infection. Eight cases were mixed infections of viruses and bacteria, four of which were viral infection combined with Bordetella pertussis. The 29 positive samples were collected from people of different age groups, including two from 31-40 years old (1.96%, 2/102 ), three from 41-50 years old (1.59%, 3/189), five from 51-55 years old (1.94%, 5/257), and 19 from 56-60 years old (4.59%, 19/414). Samples from the people aged 56-60 years accounted for the most (39.81%, 414/1 040), as well as the infection rate in this age group. Conclusions:In autumn and winter, respiratory pathogenic microorganism nucleic acid test should be performed when collecting plasma samples from donors aged 56-60 years in addition to meeting the requirements of the Chinese Pharmacopoeia. It is also suggested to conduct respiratory pathogenic microorganism nucleic acid test on pooled plasma and blood products.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of genital herpes in China from 2010 to 2023 and provide evidence for the prevention and control of genital herpes.Methods:The reported data of genital herpes cases in 31 provinces (autonomous regions and municipalities) in China from 2010 to 2023 were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Software Joinpoint 5.2.0 was used to analyze the epidemiological characteristics of genital herpes, software ArcGIS 10.5 was used for spatial autocorrelation analysis, and software SaTScan 10.2.3 was used for spatiotemporal scanning analysis.Results:The reported incidence rate of genital herpes increased from 1.58/100 000 to 2.00/100 000 in China from 2010 to 2023, with an average annual percentage change of 0.90%. The upward trend of reported incidence rate was significant ( t=2.35, P=0.037). There was a positive spatial autocorrelation in the reported incidence of genital herpes with the global Moran's I ranging from 0.36 to 0.51 (all P<0.001). Local spatial autocorrelation analysis showed that the number of hotspots increased from 144 in 2010 to 232 in 2023, mainly distributed in provinces Zhejiang, Guangdong, Guangxi, Chongqing and Hunan. The number of hotspots in of Chongqing, Sichuan, Yunnan and Guizhou increased significantly from 7 to 57. A total of 67 spatiotemporal clusters were detected by spatiotemporal scanning analysis, mainly distributed in Guangdong from 2011 to 2015, in Zhejiang and Fujian from 2015 to 2019, and in Chongqing and Guizhou from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence of genital herpes in China showed an upward trend, and there was an obvious spatiotemporal clustering of genital herpes. The distribution of hotspots was basically consistent with the distribution of spatiotemporal clustering areas, mainly distributed in the southeastern coastal area and southwestern region, and the spatiotemporal clustering areas gradually changed from the southeast coastal area to the southwest region.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

The 60th annual meeting of the European Association for the Study of Diabetes(EASD), held in Madrid, Spain, in September 2024, convened leading physicians and researchers from more than 130 countries. This premier event shared and discussed advances in diagnosis and treatment, as well as future trends in diabetes and metabolic disease research. Key topics included the presentation of the Claude Bernard Prize, advancements in diabetes management strategies, the interplay between obesity and diabetes, novel therapeutic developments, and emerging diagnostic and treatment approaches for metabolic dysfunction-associated steatotic liver disease.

Gastric polyps, as a common digestive system disease, have shown an increasing detection rate and are regarded as one of the precancerous states of gastric cancer. In TCM, gastric polyps can be classified as diseases such as "stomachache" and "fullness and distension in the stomach". TCM holds that the disease is often related to the accumulation of pathogenic factors such as phlegm and blood stasis in the body to form "kenang", which has the characteristics of insidiousness, stubbornness, and recurrence. Deficiency of healthy qi and disorder of qi movement can lead to the adhesion of phlegm and blood stasis, which highly aligns with the etiology and pathogenesis of gastric polyps. The treatment principles are promoting blood circulation to remove blood stasis, regulating qi movement, and strengthening the body resistance to consolidate the essence. Understanding the etiology, pathogenesis, and treatment principles of gastric polyps from the theory of "kenang" has important guiding significance for clinical diagnosis and treatment, providing new ideas and methods for the treatment of gastric polyps.

Objective To investigate the clinical efficacy and impact on psycho-behavioral as-pects of sublingual immunotherapy with dermatophagoides farinae drops in children with multiple al-lergies and young-age allergic rhinitis(AR).Methods A total of 139 children with AR sensitized to mites who were treated at the Second Affiliated Hospital of Nanjing Medical University were retrospec-tively selected.Based on the types of allergens,they were divided into single-allergen group and mul-tiple-allergen group,and into young-age group(≤4 years old)and older-age group(＞4 years old)according to age.Visual Analogue Scale(VAS),Total Nasal Symptom Score(TNSS),Child Behav-ior Checklist(CBCL)score,and serum total immunoglobulin E(IgE)levels were compared before treatment and at 6 and 12 months after treatment.Results A total of 123 children completed one-year of sublingual immunotherapy and clinical observation.Compared with pre-treatment,the VAS scores,TNSS,and serum total IgE concentrations of children decreased at 6 and 12 months after desensitization treatment.Moreover,the VAS scores,TNSS,and serum total IgE concentrations at 12 months of treatment were lower than those at 6 months(P＜0.05).Compared with pre-treatment,after 12 months of desensitization treatment,the scores of social withdrawal,anxiety/depression,somatic complaints,and hyperactivity items in children decreased(P＜0.05).After 6 and 12 months of desensitization treatment,the VAS scores and TNSS in the multiple-allergen group were lower than those in the single-allergen group(P＜0.05).Compared with pre-treatment,the serum total IgE concentrations in both the single-allergen group and the multiple-allergen group decreased at 6 and 12 months after treatment,with statistically significant differences(P＜0.05).Before treat-ment,the serum total IgE concentration in the older-age group was higher than that in the young-age group(P＜0.05).Conclusion Sublingual immunotherapy can achieve significant efficacy in chil-dren with multiple allergies and young-age(≤4 years old)AR,and shows better efficacy in chil-dren with multiple allergies.Meanwhile,this treatment is also beneficial for reducing the occurrence of psycho-behavioral problems in children,especially for improving hyperactive behavior.