OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group （41 cases） and a control group （41 cases） by the random number table method. The control group received routine treatment， and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators， blood pressure indicators， glucose and lipid metabolism indicators， inflammatory factors， and vascular endothelial function indicators before and after treatment in the two groups were measured， and the treatment safety was evaluated. ResultsAfter treatment， the total response rate of TCM symptoms in the observation group was 97.56% （40/41）， which was higher than that （87.80%， 36/41） in the control group （χ²=5.205， P<0.05）. After treatment， both groups showed declines （P<0.05） in systolic blood pressure （SBD）， diastolic blood pressure （DBP）， triglyceride （TG）， total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C）， fasting blood glucose， 2-hour postprandial blood glucose （2 h PG）， glycosylated hemoglobin （HbA1c）， fasting insulin （FINS）， Homeostatic Model Assessment for Insulin Resistance （HOMA-IR）， body mass index （BMI）， waist circumference （WC）， waist-to-hip ratio （WHR）， leptin （LEP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， endothelin-1 （ET-1）， and inducible nitric oxide synthase （iNOS）. Moreover， the declines in the observation group were more obvious than those in the control group （P<0.05， P<0.01）. After treatment， both groups showed elevated levels of high density lipoprotein cholesterol （HDL-C）， adiponectin （ADP）， nitric oxide （NO）， and endothelial nitric oxide synthase （eNOS） （P<0.05）， and the above indexes in the observation group were higher than those in the control group （P<0.01）. ConclusionUnder the guidance of the thought of treating disease before its onset， modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity， reducing inflammation， and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions， being worthy of clinical application and promotion.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

[Objective] To explore the diagnosis and treatment experience of tension hydrocele. [Methods] The clinical data of 2 patients with tension hydrocele treated in our hospital were retrospectively analyzed.Relevant literature was retrieved to analyze the clinical characteristics of this disease. [Results] Case 1 was diagnosed due to swelling and pain of the left scrotum after trauma for more than one month, which worsened for one day.Physical examination showed high tension in the left scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the left testis disappeared.Emergency left scrotal exploration and hydrocelectomy were performed.There was no sign of testis torsion during the operation.Case 2 was diagnosed mainly due to hydrocele of the right testis for 1 year, which worsened for 1 week and complicated with testis distension and pain.Physical examination showed high tension in the right scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the right testis decreased.After 40ml of fluid was extracted under ultrasound monitoring, the blood flow signal in the right testis recovered.Hydrocelectomy was performed the next day.During the follow-up of 8 months, there was no recurrence of hydrocele.A search of domestic and foreign literature showed that there were no reports in domestic literature, while a total of 11 cases were reported in foreign literature. [Conclusion] Tension hydrocele of the testis is a rare emergency of the scrotum.Surgery or decompression should be performed as soon as possible to restore testicular blood supply, and hydrocelectomy should be performed simultaneously or in stages to prevent recurrence.

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 effectiveness of modified single patellar tunnel medial patella femoral ligament (MPFL) reconstruction in the treatment of recurrent patellar dislocation. METHODS: Between January 2023 and June 2023, a total of 61 patients with recurrent patellar dislocation who underwent MPFL reconstruction with autologous semitendinosus were enrolled and divided into 2 groups using random number table method. In the patellar anchor group, 31 patients were treated with MPFL reconstruction with double medial patellar anchors, and 30 patients in the patellar tunnel group were treated with MPFL reconstruction with single patellar tunnel. The femoral ends of both groups were fixed with absorbable compression screws. There was no significant difference in baseline data such as gender, age, side, tibial tubercle-trochlear groove (TT-TG), Q angle, Caton-Deschamps index, number of dislocation, and preoperative Kujala score, preoperative patellar inclination angle ( P>0.05). Patellar tunnel, patellar anchor position, patellar reduction, and the patellar inclination angle were measured by CT scan after operation. Kujala score was used to evaluate the function of knee joint before operation, at 2 weeks and 1, 3, 6, 12 months after operation. Incision aesthetic satisfaction score was performed at 3 months after operation. The signal-to-noise quotient (SNQ) of the transplanted tendon was measured by knee MRI at 12 months after operation to compare the maturity of the graft between the two groups. RESULTS: There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Knee CT reexamination showed that the patellar tunnel and the patellar anchor position were consistent with the intraoperative fluoroscopy. There was no significant difference in the difference of the patellar inclination angle between the two groups before and after operation ( P>0.05). All patients were followed up 12-14 months (mean, 12.8 months). There was 1 case of patellar anchor suture rejection in patellar anchor group, and the wound healed after debridement and dressing change. During the follow-up, there was no complication such as recurrence of patellar dislocation, infection and postoperative stiffness. The Kujala scores of the two groups significantly improved at each time point after 1 month of operation when compared with those before operation ( P<0.05), and the Kujala scores of the two groups returned to normal levels at 3 months after operation. The Kujala score in the patellar tunnel group was significantly higher than that in the patellar anchor group in the very early stage (2 weeks) ( P<0.05), and there was no significant difference between the two groups at other time points ( P>0.05). Patients in the patellar tunnel group were significantly better than those in the patellar anchor group in the score of incision aesthetic satisfaction at 3 months after operation and the SNQ at 12 months after operation ( P<0.05). CONCLUSION Modified single patellar tunnel MPFL reconstruction was used to treat patients with recurrent patellar dislocation without pathological TT-TG. The slide-fixation structure formed by single patellar tunnel positioning provides a variable degree of freedom for the reconstructed MPFL, which shows good effectiveness in the very early stage of the rehabilitation process.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Plastic Surgery Procedures/methods* ; Adult ; Patellar Ligament/surgery* ; Recurrence ; Treatment Outcome ; Young Adult ; Adolescent ; Patella/surgery* ; Suture Anchors ; Hamstring Tendons/transplantation* ; Knee Joint/surgery* ; Transplantation, Autologous

Objective To investigate the effect of resveratrol on the tumor microenvironment in osteosarcoma. Methods A C57BL/6 xenograft mouse model was established and treated with resveratrol. Single-cell sequencing was performed to analyze changes in the tumor microenvironment. Immunohistochemistry was used to assess immune cell infiltration, while Western blotting was conducted to examine alterations in cellular signaling pathways. Results Resveratrol significantly inhibited the proliferation of LM8 osteosarcoma cells in C57BL/6 mice compared to the control group. Additionally, CD8⁺ T cell recruitment was enhanced. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was notably downregulated in LM8 osteosarcoma cells following resveratrol treatment. Conclusion Resveratrol promotes CD8⁺ T cell infiltration by inhibiting the JAK2/STAT3 signaling pathway, suggesting its potential as a therapeutic agent in osteosarcoma treatment.
Osteosarcoma/genetics* ; STAT3 Transcription Factor/genetics* ; Resveratrol/pharmacology* ; Animals ; Janus Kinase 2/genetics* ; Signal Transduction/drug effects* ; Tumor Microenvironment/immunology* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice ; Humans ; Cell Proliferation/drug effects* ; Bone Neoplasms/metabolism* ; CD8-Positive T-Lymphocytes/drug effects* ; Xenograft Model Antitumor Assays

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