ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Objective To establish a trimethyltin chloride (TMT) -induced learning and memory impairment model in rats, and to investigate the protective effects and potential mechanisms of ferulic acid. Methods Specific pathogen-free male SD rats were randomly divided into control group, TMT intoxication group, fluoxetine group and 25, 50, 100 mg/kg ferulic acid group. The rats in the last five groups were injected with a dose of 8 mg/kg body weight TMT solution, and the rats in control group were injected with the same volume of 0.9% sodium chloride solution. After 24 hours of TMT injection, the rats in fluoxetine group were treated 10 mg/kg body weight of fluoxetine, the rats in the three ferulic acid groups were treated with ferulic acid at doses of 25, 50, and 100 mg/kg body weight, respectively. The rats in the control group and TMT intoxication group were treated with the same volume of 0.9% sodium chloride solution, once per day for continuous gavage for 28 days. Morris water maze experiment and light-dark box test were used to assess the learning and memory abilities of the rats. The mRNA and protein expressions of nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the rat hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the rat hippocampus were detected by enzyme-linked immunosorbent assay. Results Compared with the control group, rats of TMT intoxication group on day four had prolonged escape latency (P<0.05), fewer platform crossing (P<0.05), shorter time spent in the target quadrant and shorter latency to enter the dark compartment (all P<0.05). The mRNA and protein relative expression of NF-κB, TNF-α and IL-1β increased (all P<0.05), ROS and MDA levels increased (all P<0.05), SOD and CAT activities decreased (all P<0.05) in the rat hippocampus of TMT intoxication group on day four compared with that of the control group. Except for the terms of escape latency and target quadrant period of the rats in the 25 mg/kg ferulic acid group, rats in three ferulic acid groups on day four had lower escape latency (all P<0.05), more platform crossing (all P<0.05), longer period in the target quadrant and longer latency to enter the dark compartment (all P<0.05), compared with TMT intoxication group. Except for the relative protein expression of TNF-α in the rats of 50 mg/kg ferulic acid group, the mRNA and protein expression of NF-κB, TNF-α and IL-1β decreased (all P<0.05), ROS and MDA levels were reduced (all P<0.05), and the activities of SOD and CAT increased (all P<0.05) in the hippocampus of rats of 50 and 100 mg/kg ferulic acid groups compared with TMT intoxication group. Conclusion Ferulic acid can reverse TMT-induced learning and memory impairment in rats, and its mechanism of action may be related to alleviating oxidative stress damage and excessive inflammatory response in rat hippocampus.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.

Objective:To systematically evaluate the correlation between chronic periodontitis and postmenopausal osteoporosis (PMOP).Methods:Electronic searches were conducted on Cochrane Library, Pubmed, Embase, Ovid, CNKI, CBM, VIP, and WF databases to collect research literature on the correlation between chronic periodontitis and PMOP. The Newcastle Ottawa Scale (NOS) criteria were used to evaluate the quality of the included literature, and RevMan 5.3 software was used for meta-analysis. The outcome measures were clinical attachment loss (CAL), probing depth (PD), plaque index (PI), calculus index (CI), bleeding on probing (BOP), and simplified oral hygiene index (OHI-S).Results:A total of 16 articles were included, with a total of 1587 patients. Compared with the postmenopausal non osteoporosis group, the osteoporosis group showed significant abnormalities in CAL [standardized mean difference (SMD)=1.09, 95% CI: 0.62-1.57, P<0.001], PD(SMD=0.71, 95% CI: 0.28-1.14, P<0.001), PI(SMD=0.43, 95% CI: 0.29-0.56, P<0.001), and OHI-S(SMD=0.28, 95% CI: 0.22-0.35, P<0.001) indicators, as well as in BOP(SMD=0.01, 95% CI: -0.48-0.49, P=0.97) and GI(SMD=0.01, 95% CI: -0.48-0.49, P=0.97). At the level of 0.24 and 95% CI: -0.34 to 0.81, P=0.42, there was no statistically significant difference. Conclusions:Women with PMOP exhibit more significant changes in indicators such as CAL, PD, PI, and OHI-S, suggesting that postmenopausal women with osteoporosis are more likely to suffer from periodontitis.

Objective To explore the effect of different transcranial pulse current stimulation(tPCS)program on the elimination of fatigue in physical cognitive mixed tasks.Methods Thirty healthy college athletes were randomly divided into group Ⅰ'and groupⅡ',each of 15.Then,both groups of sub-jects exercised on power bicycles.Ten subjects were screened from Group Ⅰ'and Ⅱ'meeting the crite-ria of moderate and severe physical cognitive mixed task fatigue using the Rating of Perceived Exer-tion respectively.Both groups received five tPCS interventions.Before and after each intervention,the subjects were tested for heart rate variability(HRV)and oxygenated hemoglobin(HbO2)concentration,and the effect of different stimulations on the fatigue elimination in physical cognitive mixed tasks of different severities were measured.Meanwhile,the HRV measurements included root mean square of difference between adjacent R-R intervals(RMSSD),standard deviation of all normal-to-normal inter-vals(SDNN),high frequency(HF)and low frequency(LF).Results①After tPCS intervention,the aver-age SDNN,HF and HbO2 increased significantly(P<0.05),while the average IF decreased significantly(P<0.05).②In physical cognitive mixed task of moderate fatigue,the biggest change of each index ap-peared after the tPCS program D(20 min,sensory intensity).③In the physical cognitive mixed task of severe fatigue,the change range of each index was the largest after the tPCS program C(20 min,sensory intensity + 0.2 mA).Conclusion ①After physical cognitive mixed tasks,different tPCS stimu-lation programs have different effects on the elimination of fatigue with an optimal"stimulant dose".②The effects of five intervention programs on the elimination of physical fatigue of athletes are as fol-lows:For the elimination of moderate fatigue of physical cognitive mixed task,program D of tPCS(20 min,sensory intensity)has the greatest effect,while for the elimination of severe fatigue of physical cognitive mixed task,program C of tPCS(20 min,sensory intensity + 0.2 mA)has the greatest effect.