After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective:To explore the relationship between insomnia and osteoporosis.Methods:Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio ( OR) and 95% confidence interval ( CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran′s Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results:The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% ( OR=1.007, 95% CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs ( Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10 -5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results ( P=0.059), and radial MR did not detect any outliers. Conclusion:Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

This article summarizes the clinical experience in treatment of refractory tinnitus with He's santong therapy of acupuncture (three techniques of acupuncture to remove the blockage and promote circulation). Refractory tinnitus is characterized by a mixture of deficiency and excess, which is implicated in the dysfunction of zangfu organs, resulting in physical and mental injuries. In association with the complicated conditions of the diseases and etiology, He's santong therapy of acupuncture is adopted. The needling with filiform needles acts directly on the affected site to regulate the mind and improve the hearing, the fire needling works on removing the refractory illness and blockage through heating up, and bloodletting on activating blood circulation and promoting qi flowing to eliminate the pathogens. The three techniques of acupuncture co-work on harmonizing the mind, promoting the circulations in the ear to stop tinnitus.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Middle Aged ; Adult ; Female ; Acupuncture Points

Background/Aims: Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are disorders of esophageal peristalsis and esophagogastric junction outflow, respectively, which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES. Methods: Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts.Patients with a prior diagnosis of diabetes mellitus, chronic Chagas’ disease, opioid use, or CREST syndrome were excluded from the study. Results: Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms. Conclusions Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis

OBJECTIVE Designing and synthesizing ursolic acid prodrugs to improve the water solubility and anti-multiple sclerosis(MS) activity of ursolic acid. METHODS succinic acid, dipeptide amino acid and the amino acids segments of side chains of isavuconazole wers selected according to the prodrug strategy, combined with 3-position hydroxyl of ursolic acid via condensation and esterification reaction. Using ultraviolet-visible spectrophotometry to determine the water solubility of prodrugs, and establish the experimental allergic encephalomyelitis mice model for its anti-MS efficacy evaluation. RESULTS Three prodrugs were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and LCMS(ESI). The water solubility of prodrugs 1 and 2 was over 110 times higher than ursolic acid, and that of prodrug 3 was over 200 times higher than ursolic acid. The in vivo anti-MS activity results showed that the three prodrugs showed significant anti-MS activity, among which prodrug 1 showed significantly better anti-MS activity than ursolic acid group. The mechanism might be through inhibition of peripheral inflammatory cell infiltration into the center and anti-demyelination, so as to exert the anti-MS activity. The metabolism of prodrug 1 in vivo showed that the exposure of prodrug 1 in vivo was 6 times that of ursolic acid, indicating that prodrug 1 might exert anti-MS activity mainly as sodium prototype. CONCLUSION Prodrug 1 has great anti-MS potential, which is worthy of further study. This study provides some basis and useful guidance for the development of ursolic acid prodrugs with anti-MS activity.

During a radiological or nuclear emergency, iodine thyroid blocking is an urgent protection action to prevent or reduce the absorption of radioactive iodine by thyroid. Although potassium iodide (KI) administration is recommended by WHO guidelines for iodine prophylaxis following nuclear accidents and is also widely implemented in most national guidelines, the scientific evidence for the guidelines lacks as the guidelines are mostly based on expert opinions and recommendations. This paper introduces the development and revision of WHO guidelines for iodine thyroid blocking published in 1989 and 1999, as well as the revision methods and main recommendations of the guidelines published in 2017, which supports the use of iodine thyroid blocking during a radiological or nuclear emergency.

Objective: To understand current situation of e cigarette use and associated factors in primary and secondary school students in Beijing, in order to promote the construction of smoke free schools. Methods: During April to June in 2019, PPS sampling was used to select primary schools, secondary schools and trade schools. In each selected school, randomly sampling method was conducted until the sample size was reached. There were 18 312 students included in the analysis. Surveillance information mainly included the current situation of electronic cigarette use and associated factors. Results: Among primary and secondary school students who have known about e cigarettes, female students were less likely to use e cigarettes than male students ( OR = 0.47 , 95% CI =0.42- 0.54 ). After entering the second year of junior high school, the possibility of using e cigarettes increased. Smoke free home was associated less e cigarettes usage ( OR =0.78, 95% CI =0.69-0.88). Primary and secondary school students with average daily allowance of 30~<150 yuan and no less than 150 yuan were 1.43 (95% CI =1.22-1.67) times and 2.24 (95% CI =1.79-2.79) times more likely to use e cigarettes than those with 0-10 yuan allowance, respectively. The probability of using e cigarettes among primary and secondary school students who have not tried using cigarettes was only 16.4% compared with those who have tried cigarettes ( OR =0.16, 95% CI =0.14-0.19). Conclusion It is necessary to curb the prevalence of e cigarettes among primary and secondary school students. Actions need to be taken urgently to fill in the gaps or correct the mistakes in children and adolescents cognition of e cigarettes, and to adopt more innovative methods to scientifically guide children and adolescents to stay away from e cigarettes.