ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

The inheritance, innovation, and development of traditional Chinese medicine(TCM) need to be based on Chinese medicinal materials. The TCM seed industry is the source of TCM production, which is related to the stable supply and quality safety of TCM. This paper summarizes the basic situation of the TCM seed industry and introduces relevant policies and regulations to TCM seeds in the seed industry and the TCM field. At present, the Management Measures of TCM Seeds and Seedlings has not yet promulgated, and TCM seeds are classified as non-major crops in the category of crops for management. This paper also describes the current situation of TCM seed and seedling system construction, which is in the development stage, from six aspects, including the construction of TCM seed industry technical support system; the establishment of TCM seed standard; the construction of germplasm resource preservation system; TCM seed testing, variety registration, and variety protection; production and management of TCM seeds; TCM seed supervision. According to the development status of the TCM seed industry, four problems are put forward, including imperfect systems and standards relevant to TCM seeds, insufficient supervision and law enforcement regarding TCM seeds, insufficient policy measures and capital investment to promote the development of the industry, and the industry's falling into a low-level cycle.Accordingly, four suggestions are provided, including improving laws, regulations, and policies, perfecting standards and norms,strengthening supervision and law enforcement, and promoting support system construction, in order to boost the high-quality development of the TCM seed industry.
Seeds/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/standards* ; Plants, Medicinal/chemistry*

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To predict and verify the mechanism of Naoan capsules(NAC)in treatment of ischemic stroke(IS)by network pharmacology,Gene Expression Omnibus(GEO)database,and molecular docking technology.Methods The active components in NAC were collected using the Traditional Chinese Medicine System Pharmacological Analysis Platform,and the disease-related differential genes were screened using GEO database.After screening and obtaining the common targets of the two,the compound disease network was constructed by Cytoscape 3.8.2 software.At the same time,protein-protein interaction networks were created to identify candidate targets for NAC treatment of IS,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed.Finally,core targets were verified by molecular docking technology.Results A total of 56 candidate compounds and 18 544 disease-related differential genes were screened.Further,quercetin,kaempferol,luteolin and baicalein were found to be the key active compounds of NAC in the treatment of IS through the compound disease network.In the search of PPI network core,eight key targets for NAC treatment of IS were screened,including mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma factor 2(Bcl-2),cysteinylaspartate specific protease 3(CASP3),etc.In addition,the key pathways of NAC treatment of IS are mainly concentrated in lipid and atherosclerosis,advanced glycation end products and receptor for advanced glycation end products(AGE-RAGE),tumor necrosis factor(TNF),interleukin17(IL-17),C-type lectin receptor,apoptosis,hypoxia-inducing factor-1(HIF-1),MAPK and other signaling pathways.Finally,the molecular docking results showed that the key active compounds(quercetin,kaempferol,luteolin and baicalein)had good binding force with the 8 key targets,which initially verified the results of network pharmacology.Conclusion NAC plays a role in the treatment of IS through multi-component,multi-target and multi-pathway.

Objective To analyze the efficacy of bevacizumab combined with paclitaxel+carboplatin in the treatment of recurrent/metastatic cervical cancer,and to explore the influence on survival prognosis of patients.Methods Patients with recurrent/metastatic cervical cancer were divided into control group and treatment group according to different treatment methods.The control group received paclitaxel combined with carboplatin chemotherapy regimen(intravenous infusion of 170 mg·m-2 paclitaxel and carboplatin(AUC=5 mg·mL-1·min)for 3 weeks as a course of chemotherapy),and the treatment group was given bevacizumab on the basis of control group,intravenous infusion of 15 mg·kg-1 bevacizumab,once every 3 weeks.Both groups were treated for 3 cycles of treatment by taking 3 weeks as 1 treatment cycle.The clinical efficacy,levels of serum tumor markers,quality of life,survival prognosis and occurrence of drug-related adverse reactions during treatment were compared between the two groups.Results There were 41 cases in treatment group and 48 cases in control group.After treatment,the overall response rate(ORR)of treatment group and control group were 31.71％(13 cases/41 cases)and 14.58％(7 cases/48 cases),with no statistical significance(P＞0.05).After treatment,the disease control rate(DCR)in control group and treatment group were 62.50％(30 cases/48 cases)and 82.93％(34 cases/41 cases);the squamous cell carcinoma antigen(SCCA)levels were(3.58±0.73)and(2.52±0.57)ng·mL-1;carbohydrate antigen 19-9(CA19-9)levels were(23.60±4.29)and(19.19±3.72)U·mL-1;carbohydrate antigen 15-3(CA15-3)levels were(27.13±5.36)and(22.86±3.94)U·mL-1;carbohydrate antigen 125(CA125)levels were(39.24±6.88)and(26.47±5.09)U·mL-1;the overall improvement rates of quality of life were 41.67％(20 cases/48 cases)and 73.17％(30 cases/41 cases),the progression-free survival times were 8.67 months(95％CI:7.82-9.53)and 10.25 months(95％CI:9.68-10.81),the total survival times were 9.96 months(95％CI:9.13-10.79)and 11.47 months(95％CI:11.00-11.93),all with significant difference(all P＜0.05).There were no statistically significant differences in the incidence of nausea and vomiting,leukopenia,thrombocytopenia and liver-kidney function impairment between both groups(all P＞0.05).Conclusion Bevacizumab combined with chemotherapy has significant efficacy in the treatment of recurrent/metastatic cervical cancer,and it can reduce the levels of serum tumor markers,enhance the quality of life,and improve the survival prognosis,and it has good safety.

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.