Objective:To explore of auditory-vestibular function and inner ear imaging features of patients with Meniere's disease（MD） at different clinical stages. Methods:The clinical data of 110 patients with unilateral MD who were admitted from January 2023 to March 2024 were collected, and all patients were staged according to the results of pure tone hearing threshold test, including 13 patients with stage Ⅰ, 18 cases with stage Ⅱ, 65 cases with stage Ⅲ, and 14 cases with stage Ⅳ. All patients were tested for vestibular function, including caloric tests, vestibular evoked myogenic potentials（VEMPs）, vHIT and sensory integration tests（SOT）. The sites of endolymphatic hydrops were evaluated by intravenous endotogidolinium-based MRI, twenty-seven patients completed electrocochleography. Results:①The disease course time of patients with different stages was different, and the disease course time of stage Ⅰ and Ⅱ was shorter than that of stage Ⅲ and Ⅳpatients（P<0.05）. ②No statistical differences were found in clinical data or vestibular function between normal and abnormal ECochG groups（P>0.05）. ③The results of caloric tests showed that the UW% values of stage Ⅲ（45.5±14.79） and stage Ⅳ （51.57±22.44） were higher than those of stageⅠ（31.2±14.9） and stage Ⅱ（33.5±13.31）, there were statistically significant differences between stage Ⅰ and stage Ⅱ with stage Ⅲ and Ⅳ groups（P<0.05）, the total abnormal rate of cVEMP was 62.72%, there was a statistically significant difference between stageⅠand stage Ⅲ with the stage Ⅳ group（P<0.05）, the total abnormal rate of oVEMP was 71.82%, the difference between stage Ⅰ and stage Ⅳ group was statistically significant（P<0.05）. The total score of SOT comprehensive balance gradually decreased with the increase of clinical stage, and there was a significant difference between the stage Ⅰ and Ⅳ groups（H=26.08, P<0.01）, and there was a statistically significant difference in the rate of vestibular dysfunction of SOT between the two groups（χ²=6.7, P<0.05）. ④Patients with vestibular and cochlear endolymphatic hydrops, and patients with simple cochlear or vestibular had significantly differences in disease course time, clinical stages, UW% value of caloric test, abnormal rate of cVEMP and oVEMP, total SOT balance score, the rate of vestibular abnormality（P<0.01）. Among them, when the vestibular and cochlear endolymphatic hydrops are at the same time, the clinical stage of the patient is mainly stage Ⅲand Ⅳ. Conclusion:Auditory-vestibular and inner ear gadolinium-contrasted MRI examinations in clinical practice provide a supplementary reference for judging vestibular function and the type of endolymphatic hydrops.
Humans ; Meniere Disease/diagnostic imaging* ; Ear, Inner/physiopathology* ; Male ; Magnetic Resonance Imaging ; Female ; Middle Aged ; Vestibule, Labyrinth/diagnostic imaging* ; Adult ; Vestibular Evoked Myogenic Potentials ; Aged ; Audiometry, Pure-Tone ; Caloric Tests ; Vestibular Function Tests

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

ObjectiveTo explore the effect and possible molecular mechanism of Qinghua Yichang Formula （清化益肠方， QYF） in treating acute radiation-induced intestinal injury mice via NOD-like receptor thermal protein domain associated protein 3 （NLRP3）. MethodsSixty C57BL/6J mice were randomly divided into control group， model group， pre-modeling medication group， post-modeling medication group， inhibitor group， and QYF plus inhibitor group， with 10 mice in each group.Except for the control group， the other five groups were irradiated with a single full dose to establish the acute radiation-induced intestinal injury mice model. The pre-modeling medication group and the QYF plus inhibitor group were continuously given 4 g/ml of QYF decoction by gavage before modeling， 0.2 ml each time， once a day for 7 days. The post-modeling medication group， pre-modeling medication group and QYF plus inhibitor group were given 4 g/ml of QYF decoction for 14 days after modeling. The control group， model group and inhibitor group were given 0.2 ml of normal saline once a day for 14 consecutive days. Two hours after irradiation， the inhibitor group and the QYF plus inhibitor group were given an intraperitoneal injection of 0.2 ml of the NLRP3 inhibitor MCC950 （concentration： 10 mg/kg）， once every two days. To observe the pathological changes in intestinal tissues， hematoxylin-eosin （HE） staining was used. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of NLRP3 in intestinal tissues. Immunohistochemistry was used to detect the expression level of NLRP3， Caspase-1 and GSDMD in intestinal tissues. The proportion of CD4⁺ and CD8⁺ T cells in the spleens of mice were detected by flow cytometry. ELISA was used to determine the levels of IFN-γ， IL-18， and IL-1β in mice serum. ResultsHE staining showed no lesions in the intestinal tissue of mice in the control group. The mice in the model group had shortened intestinal villi， thinned mucosal layers， multifocal mucosal necrosis in the lamina propria， and local neutrophil infiltration. The pathological damage of intestinal tissue of mice in each medication group was improved to varied degrees， among which the QYF plus inhibitor group showed most obvious improvement. Compared to those in the control group， the protein and mRNA expression levels of NLRP3 in the intestinal tissue of mice in the model group significantly increased， with higher NLRP3， Caspase-1， and GSDMD protein expression in the intestinal tissue， increased proportion of CD4⁺ T cells in spleen， decreased proportion of CD8⁺ T cells， and increased levels of IFN-γ， IL-18 and IL-1β in serum （P＜0.05）. Compared to those in the model group， the above indicators in the other medication groups were all improved （P＜0.05）.The NLRP3， Caspase-1， and GSDMD proteins in the pre-modeling medication group were lower than those in the post-modeling medication group （P＜0.05）； and the NLRP3 mRNA level in the QYF plus inhibitor group was lower than that in the inhibitor group （P＜0.05）. ConclusionQYF may play a role in preventing and treating acute radiation-induced intestinal injury by inhibiting the expression of NLRP3.

Transcatheter aortic valve implantation (TAVI) is an important alternative in treating high-risk patients with aortic valve regurgitation. Transcatheter tricuspid valve implantation (TTVI) is also an important treatment option for high-risk patients with tricuspid regurgitation. We reported a 72-year male patient who underwent TAVI due to severe aortic valve regurgitation using a J-Valve. During a two-year follow-up, the patient developed secondary tricuspid regurgitation to atrial fibrillation, and subsequently received TTVI using a LuX-Valve. Following the interventions, the patient's symptoms were significantly improved, and echocardiography indicated good hemodynamic performance of both transcatheter heart valves. This case highlights the feasibility and effectiveness of performing multiple valve implantations via transcatheter approaches in high-risk elderly patients.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndromes in postoperative gastric cancer patients， and to analyse the factors associated with yang deficiency syndrome and its severity. MethodsTotally， 173 patients who underwent postoperative gastric cancer surgery and were treated in four centers nationwide from February 22， 2022 to March 21， 2023， were enrolled. General information and TCM syndromes were collected， and Diagnostic Scale for Yang Deficiency Syndrome in Gastric Malignancies was filled in. The frequency of TCM syndromes after gastric cancer surgery was analyzed， and univariate analysis and multivariate logistic regression analysis were performed on the related factors of yang deficiency syndrome versus non-yang deficiency syndrome and between different severity of yang deficiency syndrome. ResultsThe most common syndrome after gastric cancer surgery was qi deficiency （95 cases， 54.91%）， followed by yang deficiency （87 cases， 50.29%）. Patients with yang deficiency syndrome were often suffered from qi deficiency， qi stagnation， and phlegm dampness syndrome. Comparing yang deficiency syndrome with non-yang deficiency syndrome， univariate analysis showed that history of alcohol consumption， pathological stage， degree of differentiation， Lauren grade， signet ring cell carcinoma， vascular cancer thrombus， and nerve invasion were statistically significant （P＜0.05）； and multivariate logistic regression analysis showed that history of alcohol consumption， signet ring cell carcinoma， pathological stage Ⅲ， Ⅳ， and vascular cancer thrombus may be correlated with yang deficiency syndrome in postoperative gastric cancer patients （P＜0.05）. The univariate analysis showed that age， pathological stage， precancerous lesions， and body mass index grade were significantly different when compared between mild and severe yang deficiency syndrome （P＜0.05）； multivariate logistic regression analysis showed that age， low body weight， and pathological stage Ⅲ and Ⅳ might be correlated with severe yang deficiency syndrome after gastric cancer surgery （P＜0.05）. ConclusionQi deficiency and yang deficiency are common TCM syndromes in postoperative patients with gastric cancer. Alcohol consumption history， pathological staging （stage Ⅲ and Ⅳ）， signet ring cell carcinoma， and the presence of vascular cancer thrombus may be correlated with the occurrence of yang deficiency syndrome， and higher age， low body weight， and pathological staging （stage Ⅲ and Ⅳ） may be the correlates of severe yang deficiency syndrome.

Objective:To analyze the characteristics of cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC).Methods:A retrospective study was conducted. A total of 329 patients with TSCC who underwent en bloc resection of primary tumor and neck dissection in the Second Xiangya Hospital of Central South University from June 2010 to March 2018 were included. There were 283 males and 46 females, aged from 26 to 80 years. All patients underwent the modified neck dissection. The main difference between the modified neck dissection and the traditional neck dissection lay in the managements of unconventional lymph nodes. The lymphatic adipose tissues adjacent to the superior thyroid artery, the base of facial artery and the branches of external carotid artery were thoroughly dissected. The primary tumor as well as lingual artery, tissues along the lingual artery and lymph nodes in the mouth floor were resected. χ 2 test was used for comparison of count data, and linear regression model was used for multivariate analysis. Results:Cervical lymph node metastases were found in 136 patients (41.3%). Among 142 patients (T1-2cN0) with supraomohyoid neck dissection, 22 patients had pathologically occult lymph node metastases (15.5%), with a 5-year overall survival rate of 90.2%, which was similar to the 5-year overall survival rate of 92.1% in 120 patients without lymph node metastasis (χ 2=0.156, P=0.693). Multivariate linear regression analysis showed that T stage, clinical stage and unconventional lymph node metastasis were important factors for cervical lymph node metastasis in tongue cancer patients ( P<0.05). Unconventional lymph node metastases occurred in 30 patients (9.1%), including the metastases of lymph nodes in the floor of mouth (3.0%), the lingual artery (2.4%), the base of the external maxillary artery (2.1%), the superior thyroid artery (0.9%), and the external carotid artery (0.6%). There were significant differences in the unconventional lymph node metastasis rates between patients with negative and positive conventional lymph node metastases [4.9%(10/203) vs. 15.9%(20/126), χ 2=11.242, P=0.001] and also between patients with depth of invasion ≤5 mm, 5 mm 10 mm [3.1%(2/64) vs. 5.7%(6/106) vs. 13.8%(22/159), χ 2=7.907, P=0.005]. Conclusion:Supraomohyoid neck dissection can achieve reliable control efficacy in patients with cN0 tongue cancer. All patients with lymph node dissection should undergo unconventional lymph node dissection. Unconventional lymph node dissection is strongly recommended for patients with conventional lymph node metastasis.

Objective To conduct a network meta-analysis on the effectiveness of first-line immunotherapy on patients with brain metastases from advanced non-small cell lung cancer(NSCLC).Methods Two investigators conducted a computerized search of Pubmed,Embase,Cochrane,and other databases to screen the literature,extract the information,and assess the risk of bias of the included studies.The included clinical trials were statistically analyzed using R(4.1.3)software.For the study outcome indicators OS and PFS,the risk ratios(HRs),and the 95%confidence intervals(CIs)were extracted from the included studies and logarithmically transformed into effect analysis statistics.Results Six randomized controlled trials were finally included,including 327 patients with non-excludable NSCLC brain metastases.Network meta-analysis suggested that PD-1 inhibitor+CTLA-4 was more advantageous than the conventional chemotherapy for enhancing patients'OS(HR:0.13,95%CI:0.03-0.71),followed by PD-L1 inhibitor(HR:0.17,95%CI:0.04-0.74)and PD-1 inhibitor+chemotherapy(HR:0.36,95%CI:0.2-0.63).PD-1 inhibitor+CTLA-4 was also more advantageous(HR:0.37,95%CI:0.15-0.93)than the conventional chemotherapy for boosting patients'PFS,followed by PD-L1 inhibitor+chemotherapy(HR:0.44,95%CI:0.29-0.66)and PD-1 inhibitor(HR:0.48,95%CI:0.27-0.86).Conclusion Immune checkpoint inhibitor therapy improves the survival of patients with brain metastases from advanced NSCLC.In particular,the combination of PD-1 inhibitor and CTLA-4 inhibitor show excellent survival benefit.