BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Objective: To analyze the trends, gender, and age differences in the incidence of lip and oral cavity cancer in Chinese population from 1990 to 2021 and predict future incidence trends, providing a scientific basis for disease prevention and public health policy. Methods: Incidence data of lip and oral cavity cancer in Chinese population from the Global Burden of Disease (GBD) database from 1990 to 2021 were analyzed. The Joinpoint regression model was used to assess temporal trends, the age-period-cohort model was used to evaluate the independent effects of age, period, and cohort, and the Bayesian age-period-cohort model (BAPC) model was used to predict incidence trends from 2022 to 2044. Results: From 1990 to 2021, the age-standardized incidence rate of lip and oral cavity cancer in Chinese population increased from 2.39/100 000 to 3.76/100 000, and the crude incidence rate rose from 1.71/100 000 to 4.85/100 000. The incidence rate in males was higher and increased more rapidly than in females. Higher incidence rates were prevalent among older populations, a rapid increase in incidence rates occurred during 2003 to 2012, and earlier birth cohorts showed overall higher risks. BAPC predictions indicated a continued rise in incidence from 2022 to 2044. During this period, male incidence stabilized while female incidence increased at a relatively faster rate. Conclusion The incidence of lip and oral cavity cancer in Chinese population has revealed a continuous upward trend, particularly among males and older populations. Future prevention strategies should focus on these high-risk populations.

Based on the "sweat pore-qi and liquid-collaterals" theory， it is considered that the core pathogenesis of pediatric infectious mononucleosis lies in the obstruction of sweat pores， the failure of qi and liquid to disperse， and damage to the collaterals due to pathogenic toxins. Accordingly， the treatment principles proposed include unblocking the sweat pores， regulating qi and liquid， and smoothing the collaterals. In clinical practice， treatment is differentiated according to stages： initial， acute， and late stages. In the initial stage， invasion of warm pathogenic toxins into the lung defense leads to obstruction of the sweat pores， which should be treated by unblocking the sweat pores and expelling pathogens outward. In the acute stage， the obstruction of the sweat pores worsens， leading to the failure of qi and liquid dispersal， resulting in intense heat toxins with accumulation of dampness， phlegm， and blood stasis， which should be treated by promoting qi movement， resolving dampness and phlegm， clearing heat， detoxifying， and dispersing stasis to regulate qi and liquid. In the late stage， residual pathogens remain， with qi and yin deficiency and unsmooth collaterals， which should be treated by unblocking the collaterals， dissipating nodules， tonifying qi， and nourishing yin to smooth the collaterals. This approach may provide new insights for the clinical treatment of pediatric infectious mononucleosis.

This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Autophagy/drug effects* ; Rats ; Rats, Sprague-Dawley ; Interstitial Cells of Cajal/metabolism* ; Dyspepsia/physiopathology* ; Protein Serine-Threonine Kinases/genetics* ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Signaling System/drug effects* ; Humans ; Endoribonucleases/genetics* ; Multienzyme Complexes

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To review and summarize the research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years. METHODS: Relevant literature was reviewed to summarize the application of 3D printing technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps. RESULTS: The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps ( e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes. CONCLUSION The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with surgical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.
Printing, Three-Dimensional ; Tissue Scaffolds ; Humans ; Surgical Flaps/blood supply* ; Tissue Engineering/methods* ; Plastic Surgery Procedures/methods* ; Bone and Bones/surgery* ; Biocompatible Materials ; Bone Regeneration ; Bone Transplantation/methods* ; Bone Substitutes ; Osteogenesis

OBJECTIVE: To summarize the biomechanical research progress on different fixation methods in medial opening-wedge high tibial osteotomy (MOWHTO) and provide references for selecting appropriate fixation methods in clinical applications of MOWHTO for treating knee osteoarthritis (KOA). METHODS: Recent domestic and international literature on the biomechanical studies of MOWHTO fixation methods was reviewed to analyze the characteristics and biomechanical performance of various fixation techniques. RESULTS: The medial-specific osteotomy plate system has become the mainstream due to its high stiffness and stability, but issues such as soft tissue irritation and stress shielding remain. The use of filler blocks significantly enhances fixation stability and promotes bone healing when the osteotomy gap is large, reducing axial displacement by 73%-76% and decreasing plate stress by 90%. Auxiliary screws improve axial and torsional stability, particularly in cases with large correction angles, effectively preventing lateral hinge fractures. Alternative fixation methods like external fixators hold unique clinical value by minimizing soft tissue irritation and allowing postoperative adjustment. CONCLUSION There is currently no unified standard for selecting MOWHTO fixation methods. Clinical decisions should comprehensively consider factors such as bone quality, correction angle, and postoperative rehabilitation needs.
Humans ; Osteotomy/instrumentation* ; Biomechanical Phenomena ; Tibia/surgery* ; Bone Plates ; Osteoarthritis, Knee/surgery* ; Bone Screws ; External Fixators ; Knee Joint/surgery*

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*