PURPOSE: The transforming growth factor β1 (TGF-β1)/SMAD family member 3 (SMAD3) pathway, and hypoxia-inducible factor 1α (HIF-1α) are two key players in various types of malignancies including breast cancer. The TGF-β1/SMAD3 pathway can interact with HIF-1α in some diseases; however, their interaction in breast cancer is still unknown. Therefore, our study aimed to investigate the interactions between the TGF-β1/SMAD3 pathway and HIF-1α in breast cancer. METHODS: Expression of HIF-1α in serum of breast cancer patients and healthy controls was detected by quantitative reverse transcription polymerase chain reaction, and the diagnostic value of HIF-1α for breast cancer was evaluated by receiver operating characteristic curve analysis. Breast cancer cell lines overexpressing SMAD3 and HIF-1α were established. Cell apoptosis and proliferation following different treatments were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and cell counting kit-8, respectively. Expression of related proteins was detected by western blot. RESULTS: Serum levels of HIF-1α were higher in breast cancer patients than in normal controls. Both SMAD3 and HIF-1α overexpression inhibited cell apoptosis and promoted cell proliferation. Treatment with inhibitors of HIF-1α and SMAD3 promoted apoptosis in breast cancer cells and inhibited their proliferation. Overexpression of HIF-1α promoted the expression of TGF-β1 and SMAD3, while SMAD3 overexpression did not significantly affect expression of HIF-1α or TGF-β1. CONCLUSION: HIF-1α serves as an upstream regulator of the TGF-β1/SMAD3 pathway and promotes the growth of breast cancer.
Apoptosis ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Cell Count ; Cell Line ; Cell Proliferation ; Humans ; Hypoxia-Inducible Factor 1 ; Polymerase Chain Reaction ; Reverse Transcription ; ROC Curve ; Smad3 Protein ; Transforming Growth Factor beta1 ; Transforming Growth Factors*

Primary aldosteronism(PA) is one of the most common secondary hypertension, the pathogenesis is still not fully understood. Aldosterone synthase(CYP11B2) was thought to be continuously expressed in the zona glomerulosa of the adrenal cortex. In recent years, it is found that there were discontinuous CYP11B2 positive cell clusters in adrenal cortex via immunohistochemical staining, and proposed the concept of aldosterone-producing cell clusters(APCC). Thenceforwarding a growing body of studies suggest that there may be a potential causal link between APCC and PA. This article summarizes the latest studies on APCC and provide an update on the potential role of APCC in the pathogenesis of PA.

BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.

Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.

The prevalence of heart failure(HF) is increasing worldwide, and mitral regurgitation(MR) is a common manifestation in patients with end-stage HF. Currently, the indications for concomitant surgical intervention of significant preoperative MR during left ventricular assist device(LVAD) implantation are still controversial. Based on discussing the etiology, classification, and pathophysiology of functional MR in patients with end-stage HF, this paper reviews the relevant factors affecting the prognosis of such patients and the progress of research related to whether to perform mitral valve surgery to intervene in significant MR during LVAD implantation, to provide a further reference for clinical practice.

Objective To explore the risk factors of frozen shoulder,and to provide the basis for the prevention of frozen shoulder.Methods A total of 114 patients with frozen shoulder who were hospitalized in the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to August 2022 were included in case group,and 114 physical examination patients with no history of frozen shoulder were included in control group.The clinical data of two groups were collected and the risk factors of frozen shoulder were analyzed by multivariate Logistic regression.Results There were statistically significant differences in cervical radiculopathy,type 2 diabetes mellitus,hepatitis,chronic non-atrophic gastritis,lumbar disc herniation,osteoporosis and thyroid sarcoidosis between two groups(P<0.05).Multivariate Logistic analysis showed that cervical radiculopathy(OR=6.114,95%CI:1.458-25.642)and type 2 diabetes mellitus(OR=24.069,95%CI:4.023-144.007)were independent risk factors for the onset of frozen shoulder.Conclusion Patients with type 2 diabetes mellitus and cervical radiculopathy have a higher risk of frozen shoulder,and should pay attention to early prevention.

BACKGROUNDThe radial artery (RA) is becoming a popular conduit for coronary artery bypass grafting (CABG), yet data reporting the long-term results are rare. We reported our clinical, angiographic and intravascular ultrasound findings on 93 patients who had the RA used as part of the conduit for the CABG procedures during a 12-year period from June 2001 to June 2013.

METHODSA total of 118 radial artery conduits were harvested in 87 males and 6 females, age from 28 to 66 (mean 49.9) years. An "intra-operative Allen's test" was developed to safeguard blood supply to the arm and hand. A "double-clip & scissors-cut" technique was carried out to minimize the thermal injury to the radial artery from the diathermy. The left radial artery was used in 67 patients, the right in one, and bilateral radial arteries in 25 patients. One hundred and twenty-two out of 272 distal anastomoses (44.9%) were constructed with radial arteries, with an average of 2.9 grafts per patient (range 2-6).

RESULTSFollow-up angiography and intravascular ultrasound study at 3-139 postoperative months (mean 59 months) revealed a 93.1% RA patency. String sign occurred in one patient in whom the RA was directed to a big right coronary artery with a stenosis of around 50%. The patency for the internal mammary artery was 96.4%.

CONCLUSIONSThe RA is an excellent conduit that broadens the options for total arterial CABG surgery. Good graft patency could be achieved through careful harvesting techniques and choice of proper target coronary vessels.

Adult ; Aged ; Anastomosis, Surgical ; methods ; Coronary Artery Bypass ; methods ; Coronary Artery Disease ; surgery ; Female ; Humans ; Male ; Middle Aged ; Radial Artery ; surgery