ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

This study aims to review the current status and development trends of digital TCM (Traditional Chinese Medicine) specimen museums, providing a theoretical basis for their future construction. By systematically organizing literature and materials, practical experiences in platform architecture design, content planning, and technical implementation were summarized. The research results show that digital technology has significant application value in the TCM field. Currently, some Food and Drug Control Institutes have formed diverse construction achievements by integrating regional characteristics with technological innovation. However, current TCM specimen museums generally still face many challenges, such as insufficient digitalization. In conclusion, the digitalization of TCM specimen museums has become an inevitable trend in the industry. Targeted measures are urgently needed to solve existing problems and promote the sustainable development of digital TCM specimen museums. It is suggested to strengthen the standardization of data collection and storage, deepen the integration of technologies such as 3D, AR, and AI into the construction of specimen museums, and at the same time promote the spatial design combining regional culture with TCM. This will help create "one museum with one feature for one region" digital TCM specimen museums, further promoting their sustainable development and facilitating the digital inheritance of TCM.

ObjectiveTo investigate the association between insulin resistance （IR） and cardiovascular metabolic indicators， including blood pressure， blood lipids， and serum uric acid， in a middle-aged population. MethodsBased on the baseline survey of the Hong Sifang cohort of China National Salt Industry Group， a total of 575 participants were included. According to the homeostasis model assessment of insulin resistance， the participants were divided into an IR group （n=116） and a non-IR group （n=459）. Differences between the two groups were compared using the t-test and chi-square test. Multivariate logistic regression analysis was performed to evaluate the associations between IR and abnormalities in metabolic indicators. ResultsA total of 575 participants were included， including 390 men and 185 women， with a mean age of （48.58 ± 5.14） years and a mean body mass index （BMI） of （24.16 ± 2.97） kg/m². Blood pressure， serum uric acid， and blood lipid levels were significantly higher in the IR group than in the non-IR group （P<0.001）. After adjusting for potential confounders including age， sex， and BMI， IR was independently associated with hypertension， dyslipidemia， and hyperuricemia， with odds ratios （OR） and 95% confidence intervals （CI） of 2.57 （1.61-4.09）， 3.81 （2.36-6.17）， and 2.68 （1.53-4.71）， respectively （all P<0.001）. ConclusionInsulin resistance is significantly associated with multiple cardiovascular metabolic risk factors in the middle-aged population. Monitoring IR may contribute to the early prevention and control of cardiovascular diseases.

Antitumor drugs are considered pathogenic toxin-attacking agents， whose intense and biased pharmacological effects on the body may induce secondary pathological factors and subsequent pathological changes， that is， drug toxin. Its pathogenic features include rapid and marked impairment of healthy qi and constitution-dependent transformation. Zang-fu （脏腑） organs involvement is characterized by an early response of the middle jiao （焦）， later involvement of the kidney and marrow， and extension to the five zang organs， while its temporal evolution may manifest as acute injury， cumulative injury， and persistent or delayed injury. Cancer toxin， drug toxin， and deficiency of healthy qi interact to form a dynamically evolving complex pathogenic pattern. Clinically， treatment should take disease stage as the framework， toxin differentiation as the focus， and reinforcement of healthy qi as a principle throughout the course， while coordinating toxin reduction and elimination of cancer toxin with reinforcement of healthy qi. Furthermore， intervention against drug toxin should be initiated early and throughout the entire course of antitumor therapy. This framework may provide a theoretical basis for integrating traditional Chinese medicine throughout comprehensive cancer treatment.

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid