Prostate cancer （PCa） is one of the most common malignant tumors in the male genitourinary system. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a carcinogenic pathway responsible for the migration， proliferation， and drug resistance of various cancers. In recent years， as the research on the pathogenesis of PCa is deepening， the role of the PI3K/Akt signaling pathway in the development of PCa has attracted much attention. Traditional Chinese medicine， comprehensively regulating multiple components， targets， and pathways， has shown great potential in the treatment of PCa. This article reviews the research progress of traditional Chinese medicine targeting the PI3K/Akt signaling pathway in the treatment of PCa and discusses the expression of the PI3K/Akt signaling pathway in PCa， which involves inhibiting apoptosis of PCa cells， promoting the cell cycle， invasion， and migration of PCa cells， promoting tumor tissue angiogenesis， and mediating the androgen receptor. Additionally， it summarizes the single Chinese medicines that target and regulate this pathway， including Hedyotis diffusa， Taxus chinensis， Bovisc Alculus， and Atractylodis Macrocephalae Rhizoma. The active ingredients of these Chinese medicines mainly include flavonoids， alkaloids， terpenes， polyphenols， lignans， and other compounds. The Chinese medicine compound prescriptions targeting the PI3K/Akt pathway mainly include Wenshen Sanjie prescription， Jianspi Lishi Huayu prescription， Yishen Tonglongtang， Qilan prescription， Xihuangwan， and modified Shenqi Dihuangtang. This review is expected to provide a scientific basis for deeply understanding the pathogenesis of PCa and identifying potential therapeutic targets， as well as to provide new ideas for clinical research and drug development for PCa.

The tendon-bone interface is where the tendons or ligaments are connected with the bones. A spectrum of injuries may happen to the "soft-to-hard" tissue interface, including those to the rotator cuff-bone and cruciate ligament-bone interfaces, which are often precipitated by a combination of degenerative changes on the tendon-bone interface and acute or chronic injuries, thus severely impairing the patients′ motor function. In recent years, with the deepening of the interdisciplinary researches in biomechanics, mechanobiology, and sports medicine, the role of mechanical factors in the repair of tendon-bone interface injuries has attracted more and more attention and becomes a focus of the edge-cutting researches on the tendon-bone interface injuries. To this end, the authors proposed the concept of "tendon-bone interface mechanomedicine" based on an overview of the relevant researches at home and abroad. The mechanical properties of the tendon-bone interface and the effects of mechanical stimuli on its biological behavior were elucidated from the four aspects: biomechanics, mechanobiology, mechanodiagnostics, and mechanotherapy, aiming to explore the diagnostic and therapeutic strategies for tendon-bone interface injuries from the angle of mechanics and provide new perspectives and methodologies for the field of tendon-bone interface injury repair.

Diabetes mellitus erectile dysfunction(DMED)is a common diabetic-related vascular,endo-crine and neuropathy in clinical practice,and patients with DMED often present with symptoms such as difficulty in erection,prolonged erection time,poor hardness,and short sexual intercourse.The etiological mechanism is complex,and it is often closely related to many factors such as oxidative stress(OS),inflammatory response,and neurological and endocrine lesions,which often cross-react and promote the progression of DMED lesions.In recent years,relevant studies have shown that OS and ferroptosis play a key role in DMED:OS can cause neuro-logical and Abnormal endocrine function,decreased synthesis or bioavailability of penile vascular endothelium,spongy endothelial cell dysfunction and decreased smooth muscle diastolic function,resulting in penile erectile dysfunction,and ferroptosis has also been confirmed to be closely related to DMED,controlling OS and ferroptosis to improve erectile function in diabetic patients is a reasonable and effective treatment pathway,but the mechanism of action of ferroptosis leading to DMED needs to be further studied.Therefore,this article reviews the latest infor-mation on the correlation between OS and ferroptosis and DMED,aiming to provide a useful reference for exploring the mechanism of DMED,clinical prevention and treatment of DMED,and providing potential directions for future research in this field.

Idiopathic pulmonary fibrosis (IPF) is a progressive scar-forming disease with a high mortality rate that has received widespread attention. Epithelial mesenchymal transition (EMT) is an important part of the pulmonary fibrosis process, and changes in the biomechanical properties of lung tissue have an important impact on it. In this paper, we summarize the changes in the biomechanical microenvironment of lung tissue in IPF-EMT in recent years, and provide a systematic review on the effects of alterations in the mechanical microenvironment in pulmonary fibrosis on the process of EMT, the effects of mechanical factors on the behavior of alveolar epithelial cells in EMT and the biomechanical signaling in EMT, in order to provide new references for the research on the prevention and treatment of IPF.
Humans ; Epithelial-Mesenchymal Transition ; Idiopathic Pulmonary Fibrosis ; Signal Transduction

Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

Background::The CHA 2DS 2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA 2DS 2–VASc score in stroke and all-cause mortality. Methods::Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA 2DS 2–VASc score model. Results::Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA 2DS 2–VASc score significantly improved the discrimination and reclassification power of the CHA 2DS 2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA 2DS 2–VASc model for predicting all-cause mortality. Conclusions::Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA 2DS 2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

Objective:This study proposed a new clinical classification and treatment strategies for periocular arteriovenous malformation (AVM).Methods:A retrospective analysis of the cases of periocular AVM from Jan 2015 to Jan 2019 was included in this study. According to the DSA angiography results, which type of the ophthalmic artery connected with the AVMs, three types of classification were initiated: type 1 is unilateral ophthalmic artery blood supply the lesion and the central retinal artery is not involved; type 2 is bilateral ophthalmic artery blood supply and the central retinal artery is not involved; type 3 is unilateral or bilateral ophthalmic artery blood supply and the central retinal artery is involved. Type 3 can be subdivided into 3a and 3b subtypes according to the visual acuity of the affected eye. Type 3a is the presence of vision; type 3b is the loss of vision. Type 1 patients were treated with super-selective onyx embolisation of the feeding arteries of AVMs through the ocular arteries and then treated with ethanol embolotherapy; Type 2 patients were treated with bilateral super-selection onyx embolisation of the feeding arteries of AVMs through the ocular arteries and then were treated with ethanol embolotherapy; type 3a patients were treated with ethanol embolotherapy combined with surgery; type 3b patients were treated with enucleation and orbital reconstruction.Results:There were 32 cases in this study. For 6 cases of type 1, The treatment course was 1-5 sessions, with an average of 2.1 sessions. 5 cases were cured, 1 case was improved, 1 case occured minor complication (superficial tissue necrosis), which was self-healing; In 8 cases of type 2, 4 cases were treated with interventional therapy for 1-7 sessions, with an average of 2.5 sessions. 3 cases were cured, 5 cases were improved, 1 case had minor complication (superficial tissue necrosis). Among the 4 cases treated by operation, 3 cases were repaired by expanded flap, 1 case by local flap. 1 case was cured, and 3 cases was improved, without operation related complications; In 13 cases of type 3a, 3 cases was cured, 10 cases was improved, 2 cases had intervention therapy related minor complications (superficial tissue necrosis) which was self-healed, 1 case had operation related complications (small area necrosis of flap, necrosis area was treated by dressing). In 5 cases of 3b type, 2 cases were cured, 3 cases were improved, and 1 case had operation related complication (partial necrosis of flap, thedefect was further repaired by skin grafting).Conclusions:The classification of periocular arteriovenous malformations has its significance for guiding the selection of treatment strategies. Combining ethanol embolotherapy, neurological intervention techniques, and plastic and reconstructive techniques are essential to achieve better clinical outcome in the treatment of periocular AVM with minimal complications.

Objective:To assess the treatment outcome of patients with head and facial arteriovenous malformation treated with absolute ethanol embolization alone, resection alone or combined ethanol embolization-resection.Methods:Medical records of 74 patients [41 male and 33 female; age mean, ( 29.1±10.6 )years]) with head and facial arteriovenous malformation between January of 2014 and December of 2018 were reviewed retrospectively. The most common sites were ear( n=25), cheek( n=20), and lip( n=18). Based on the pattern of lesion location and extent, a classified treatment strategy including ethanol alone, surgical resection and combined ethanol embolization-resection was established to gain satisfied treatment efficacy. Results:In total, cure was achieved in 50 patients (67.6%), and improvement was achieved in 24 patients. Ethanol embolization alone was performed in 42 patients [mean, ( 2.6±1.2) sessions]. The dosage of ethanol used per single session ranged from was 1.5 to 24.0 ml. Cure was achieved in 27 patients (64.3%), and improvement was achieved in 15 patients (35.7%). Surgical resection alone was performed in 15 patients. Cure was achieved in 12 patients (80.0%), and improvement was achieved in 2 patients (20%). Local flaps were performed in 2 patients, expanded flaps in 11 patients, and free flaps in 2 patients. Combined ethanol embolization-resection was performed in 17 patients. Cure was achieved in 11 patients (64.7%), and improvement was achieved in 6 patients (35.3%). In total, cure was achieved in 50 (67.6%) patients, improvement was achieved in 24 (32.4%) patients, with a follow-up of 27.0±11.3 months. A total of 2 major complications occurred in 2 patients. One patient experienced recurrence. Lesions involving ≥2 cervicofacial subunits had a lower cure rare compared with localized lesions ( P<0.05). Treatment outcomes were not significantly related to the treatment modalities ( P>0.05). Conclusions:Surgical resection and ethanol embolization, alone or combination, should be integrated in a regimen to treat head and facial arteriovenous malformation for gaining both satisfied treatment efficacy and optimal cosmetic outcome.

Objective:This study proposed a new clinical classification and treatment strategies for periocular arteriovenous malformation (AVM).Methods:A retrospective analysis of the cases of periocular AVM from Jan 2015 to Jan 2019 was included in this study. According to the DSA angiography results, which type of the ophthalmic artery connected with the AVMs, three types of classification were initiated: type 1 is unilateral ophthalmic artery blood supply the lesion and the central retinal artery is not involved; type 2 is bilateral ophthalmic artery blood supply and the central retinal artery is not involved; type 3 is unilateral or bilateral ophthalmic artery blood supply and the central retinal artery is involved. Type 3 can be subdivided into 3a and 3b subtypes according to the visual acuity of the affected eye. Type 3a is the presence of vision; type 3b is the loss of vision. Type 1 patients were treated with super-selective onyx embolisation of the feeding arteries of AVMs through the ocular arteries and then treated with ethanol embolotherapy; Type 2 patients were treated with bilateral super-selection onyx embolisation of the feeding arteries of AVMs through the ocular arteries and then were treated with ethanol embolotherapy; type 3a patients were treated with ethanol embolotherapy combined with surgery; type 3b patients were treated with enucleation and orbital reconstruction.Results:There were 32 cases in this study. For 6 cases of type 1, The treatment course was 1-5 sessions, with an average of 2.1 sessions. 5 cases were cured, 1 case was improved, 1 case occured minor complication (superficial tissue necrosis), which was self-healing; In 8 cases of type 2, 4 cases were treated with interventional therapy for 1-7 sessions, with an average of 2.5 sessions. 3 cases were cured, 5 cases were improved, 1 case had minor complication (superficial tissue necrosis). Among the 4 cases treated by operation, 3 cases were repaired by expanded flap, 1 case by local flap. 1 case was cured, and 3 cases was improved, without operation related complications; In 13 cases of type 3a, 3 cases was cured, 10 cases was improved, 2 cases had intervention therapy related minor complications (superficial tissue necrosis) which was self-healed, 1 case had operation related complications (small area necrosis of flap, necrosis area was treated by dressing). In 5 cases of 3b type, 2 cases were cured, 3 cases were improved, and 1 case had operation related complication (partial necrosis of flap, thedefect was further repaired by skin grafting).Conclusions:The classification of periocular arteriovenous malformations has its significance for guiding the selection of treatment strategies. Combining ethanol embolotherapy, neurological intervention techniques, and plastic and reconstructive techniques are essential to achieve better clinical outcome in the treatment of periocular AVM with minimal complications.

Objective:To assess the treatment outcome of patients with head and facial arteriovenous malformation treated with absolute ethanol embolization alone, resection alone or combined ethanol embolization-resection.Methods:Medical records of 74 patients [41 male and 33 female; age mean, ( 29.1±10.6 )years]) with head and facial arteriovenous malformation between January of 2014 and December of 2018 were reviewed retrospectively. The most common sites were ear( n=25), cheek( n=20), and lip( n=18). Based on the pattern of lesion location and extent, a classified treatment strategy including ethanol alone, surgical resection and combined ethanol embolization-resection was established to gain satisfied treatment efficacy. Results:In total, cure was achieved in 50 patients (67.6%), and improvement was achieved in 24 patients. Ethanol embolization alone was performed in 42 patients [mean, ( 2.6±1.2) sessions]. The dosage of ethanol used per single session ranged from was 1.5 to 24.0 ml. Cure was achieved in 27 patients (64.3%), and improvement was achieved in 15 patients (35.7%). Surgical resection alone was performed in 15 patients. Cure was achieved in 12 patients (80.0%), and improvement was achieved in 2 patients (20%). Local flaps were performed in 2 patients, expanded flaps in 11 patients, and free flaps in 2 patients. Combined ethanol embolization-resection was performed in 17 patients. Cure was achieved in 11 patients (64.7%), and improvement was achieved in 6 patients (35.3%). In total, cure was achieved in 50 (67.6%) patients, improvement was achieved in 24 (32.4%) patients, with a follow-up of 27.0±11.3 months. A total of 2 major complications occurred in 2 patients. One patient experienced recurrence. Lesions involving ≥2 cervicofacial subunits had a lower cure rare compared with localized lesions ( P<0.05). Treatment outcomes were not significantly related to the treatment modalities ( P>0.05). Conclusions:Surgical resection and ethanol embolization, alone or combination, should be integrated in a regimen to treat head and facial arteriovenous malformation for gaining both satisfied treatment efficacy and optimal cosmetic outcome.