Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia （BPH）. MethodsThirty male SD rats were randomly divided into a sham group， a model group， a finasteride group （0.45 mg·kg^-1·d^-1）， and low-dose and high-dose groups of Guizhi Fulingwan （0.135， 0.337 5 g∙kg^-1∙d^-1）， with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg^-1∙d^-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage， and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight， volume， index， and hematoxylin-eosin （HE） staining. The serum sex hormone levels of testosterone （T）， dihydrotestosterone （DHT）， and estradiol （E₂） were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor （AR） was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group， the model group， and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry （UHPLCQ Exactive） to screen for metabolic markers and to obtain relevant metabolic pathways. ResultsCompared with those in the sham group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the model group were all elevated （P<0.05， P<0.01）， and the histomorphology showed pathological changes. Compared with those in the model group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the intervention groups showed a decreasing trend （P<0.05， P<0.01）， and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan， such as dehydrosafynol， hyoscyamine， and lumichrome， which were involved in the pathways of autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling. ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats， and its mechanism may be related to autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling.

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

OBJECTIVE: To investigate the significance of HALP score as a prognostic indicator for newly diagnosed multiple myeloma (MM). METHODS: Clinical data of 62 newly diagnosed MM patients in our hospital from January 2020 to December 2022 were collected and retrospectively analyzed. The difference in age, sex, DS stage, R-ISS stage, M protein type, serum creatinine (Scr), β₂-microglobulin (β₂-MG), blood calcium, lactate dehydrogenase (LDH), hemoglobin (Hb), albumin (ALB), platelet count (PLT), and absolute lymphocyte count (ALC) between patients with low and high HALP scores were analyzed. The prognostic value of the above indexes in newly diagnosed MM patients was analyzed by univariate and multivariate analysis. RESULTS: The optimal cut-off value of HALP score was 41 determined by X-tile software. Based on this, 62 patients were divided into a high HALP group (HALP>41, n=25) and a low HALP group (HALP≤41, n=37). The proportion of patients with Hb≥100 g/L in the high HALP group was significantly higher than that in the low HALP group (P <0.05). The median overall survival (OS) time of patients in the high HALP group and low HALP group were 29 (9-39) months and 20 (4-29) months, respectively, with statistically significant difference between the two groups (P <0.01). Univariate analysis showed that R-ISS stage, ALB, Hb, ALC and HALP were closely related to the prognosis of patients (P <0.05). COX regression multivariate analysis showed that R-ISS stage Ⅲ (HR=4.443, 95%CI : 1.480-13.343，P =0.008) and HALP≤41(HR=8.823, 95%CI : 1.858-41.910，P =0.006) were independent risk factors for shortened OS in newly diagnosed MM patients. The median OS of patients with high HALP at R-ISS stage Ⅲ was significantly higher than that of patients with low HALP at the same stage, and the difference was statistically significant (P <0.05). CONCLUSION HALP score can be used as a prognostic indicator for newly diagnosed MM patients.
Humans ; Multiple Myeloma/diagnosis* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; beta 2-Microglobulin ; Lymphocyte Count