Purpose To detect the expression of peroxiso-mal membrane protein 4(PXMP4)in breast cancer tissues and to explore the effect of PXMP4 on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of breast cancer cells.Methods Bioinformatics and immunohistochemistry(IHC)were used to detect the expression of PXMP4 in breast cancer tissues.In breast cancer cells,Western blot was used to detect the expression of Cyclin D1,E-cadherin,vimentin and N-cadherin after knockdown and overexpression of PMXP4.The proliferation ability of breast cancer cells was analyzed by CCK-8 and plate cloning assay.Scratch healing and Transwell assay an-alyzed the migration and invasion ability of breast cancer cells.Lentivirus was used to construct a PXMP4-silenced MCF-7 cell line,and the PXMP4-silenced MCF-7 cells were injected into the subcutaneous or tail vein of mice to observe lung metastasis and the number of subcutaneous tumors.Results Bioinformat-ics and IHC showed that the expression of PXMP4 in breast cancer tissues was significantly increased(P＜0.05),and the prognosis of breast cancer patients with high expression of PXMP4 was poor(P＜0.05).The clinicopathological analysis showed that the expression of PXMP4 was correlated with tumor grade and lymph node metastasis(P＜0.05).In vitro knock-down of PMXP4 inhibited the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).Conversely,overex-pression of PXMP4 promoted the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).In vivo,the number of lung metastases,the size of subcutaneous tumor,and the expression of Ki67 in tumor tissue were significantly de-creased after silenced PXMP4(P＜0.05).Conclusion PXMP4 is related to tumor grading and lymph node metastasis.PXMP4 promotes proliferation,invasion and EMT process of breast cancer cells.

Objective:To investigate the clinical efficacy of the new bridging combined internal fixation system in the treatment of irregular bone fractures.Methods:Retrospectively analyzed the complete case data of 32 patients with displaced mid-clavicle fractures treated with bridging combined internal fixation system from June 2021 to September 2023 at Suzhou Hospital of Nanjing Medical University, including 20 males and 12 females, with ages ranging from 25 to 65 years old, and an average of 37.5 years old. The operation time, operative bleeding, incision length, hospitalization days, fracture healing time, and postoperative related complications were recorded, and the shoulder joint function was evaluated by Constant-Murley scoring system at the final follow-up.Results:The operation time was (45.5±10.0) min; the hospitalization time was (5.0±2.1) days; the length of the surgical incision was (8.5±1.2) cm; the intraoperative bleeding was (25.0±10.2) mL; 32 patients were followed up until the fracture was healed, and the time of fracture healing was (4.5±2.2) months. One case of a thin female patient with thin subcutaneous tissues had a bulging of the skin and a feeling of discomfort after the operation and no complaint of discomfort after removal of the internal fixation after 6 months. After 6 months, the fracture healed and there was no complaint of discomfort after removal of the internal fixation. None of the other patients had complications such as postoperative infection, fracture non-union, or loosening of the internal fixation. The Constant-Murley score of all patients at the last follow-up points) was significantly improved compared with that of the preoperative period [(92.0±5.0) vs (50.0±6.0), P<0.05]. Conclusion:As a new type of internal fixation, the bridging combined internal fixation system has clear clinical efficacy in the treatment of displaced mid-clavicle fractures, with high plasticity of internal fixation and stable fixation in multiple planes, which provides a new choice for the treatment of displaced mid-clavicle fractures.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.

Objective:To evaluate the diagnosis and treatment of abdominal cocoon.Methods:The clinical data of 8 patients with abdominal cocoon in our hospital from Jan 2015 to Dec 2021 were retrospectively reviewed including clinical and imaging manifestations, treatment and follow-up.Results:One case was asymptomatic, and the other 7 cases suffered from recurrent abdominal pain with complete or incomplete intestinal obstruction. The median course of disease was 6 months (15 days to 40 years). Six cases underwent laparcoscopic cocoon membrane resection and intestinal adhesion lysis, of which 2 cases underwent laparotomy, one case was converted to open surgery, 4 cases underwent concomitant appendectomy. Follow-up ranged from 3 to 69 months, there were 2 cases complicating early inflammatory intestinal obstruction, 1 case suffred wound fat liquefaction and infection, 1 case with a colic 5 months after operation, and the others were doing well.Conclusions:The clinical characteristics of abdominal cocoon disease are not typical. Surgery is the main treatment. The prognosis of the disease is generally fair.

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Objective:To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA).Methods:We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis.Results:In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO 2 gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO 2 gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions:TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

Objective To evaluate the feasibility and results of laparoscopic thyroidectomy by oral and breast approach for the treatment of papillary throid carcinoma.Methods Thyoidectomy was performed in 26 cases,including 24 females and 2 males with the average age of 34 years (range 20-53 years).All patients were diagnosed throid carcinoma confirmed by FNA or B-mode ultrasound examination,a thyroid lobe or total thyroidectomy and central compartment dissection was performed by breast approach,then additional dissection of central compartment was completed through oral approach.Results Laparoscopic thyroidectomy via oral in combination with brest approach was performed successfully in all 26 cases.The mean operative time was (164 ± 13) min,including average time of oral approach of (40 ± 7) min.The mean number of lymph node dissection in central compartment was 7.42 ± 4.88,oral approach achieved additional 1.23 ± 2.21,with metastatic lymph nodes diseccted by oral approach in 3 cases.Conclusions Laparoscopic thyroidectomy via oral in combination with breast approach for the treament of papillary throid carcinoma is better than breast approach alone in central compartment dissection.

Objective To explore the changes of type H vessel during the low bone mineral density caused by iron accumulation and discuss its clinical meaning.Methods Ten 8-week old male C57BL/6J mice were used for experiments,and randomly divided into two groups:control group and iron group,and 5 mice in each group.In the iron group,0.1 g/kg of iron dextran was injected intraperitoneally once a week for 8 weeks.The control group was injected with the same amount of saline.The femoral and tibial specimens were examined by microscopic CT scan and bone tissue type H vessel immunohistochemical staining.Liver tissue from the two groups were collected for the content of iron by atomic absorption spectroscopy.All experimental data were analyzed with t-test.Results The content of hepatic iron in mice was significantly higher than that in the control group,which indicating that the model was successfully established.The tibia specimens were collected for immunostaining.The vascular area of type H at metaphyseal regions is 11.24％± 1.76％ in iron group and 30.69％±2.78％ in control group,respectively.There is significant difference between the two groups (P＜0.005).The femur specimens were collected for Micro-CT scan,the value of bone mineral density (BMD),bone volume/tissue volume (BV/TV),trabecular thickness (Tb.Th),trabecular number (Tb.N) and trabecular separation (Tb.Sp) was (0.19±0.013) g/cm3,11.92％±1.199％,(35.66±2.684) μm,(2.36±0.429)/mm and (284.41±23.197) μm in iron group and (0.37±0.023) g/cm3,35.76％± 1.336％,(62.05±2.238) μm,(5.68± 1.039)/mm and (163.23± 13.203) μm in control group,respectively.The differences between the two groups were statistically significant (P＜0.05).Conclusion Iron accumulation can lead to low BMD and suppress type H vessel formation in bone,which might provide a new experimental value for mechanism research on osteoporosis caused by iron accumulation.