[Salidroside regulates the phenotypic transformation of corpus cavernosum smooth muscle cells of rats through the PDGFR/STAT3 signaling pathway].

OBJECTIVE: To explore the mechanism of Salidroside regulating the phenotypic transformation of cavernous smooth muscle cells (CCSMCs) in rats. METHODS: Primary CCSMCs were isolated from male SD rats, cultured in hypoxic environment for 24 hours, and treated with Salidroside at 30 µg/mL. Then the expressions of HIF-1α, platelet-derived growth factor receptor (PDGFR) and phenotypic transformation-related proteins α-SMA and Collagen I were detected by Western blot. The culture system of the CCSMCs was treated with exogenous PDGF-BB at 20 ng/mL for 24 hours, and the effects of Salidroside or PDGFR inhibitor Crenolanib (100 nmol/L) were observed. The expressions of PDGFR, phosphorylated PDGFR, phenotypic transformation-related proteins α-SMA and Collagen I, STAT3, phosphorylated STAT3, STAT5 and phosphorylated STAT5 were determined by Western blot. The intervention effects of Salidroside and/or the overexpression of STAT3 were observed after stimulation of the CCSMCs by exogenous PDGF-BB, followed by detection of the expressions of phenotypic transformation-related proteins α-SMA and Collagen I, STAT3 and phosphorylated STAT3 proteins. RESULTS: The expression of HIF-1α in the CCSMCs was significantly upregulated after cultured in hypoxic environment for 24 hours (P < 0.05), suggesting the successful construction of the hypoxia model of CCSMCs. Meanwhile, the expressions of PDGFRα, PDGFRß and Collagen I were remarkably increased (all P < 0.05), and that of α-SMA markedly decreased (P < 0.05) in the CCSMCs. However, the expressions of the all the proteins above were significantly inhibited by Salidroside intervention (all P < 0.05). After stimulated by exogenous PDGF-BB for 24 hours, the phosphorylation ratios of PDGFRα, PDGFRß and STAT3 and the expression of Collagen I were significantly elevated (all P < 0.05), that of α-SMA remarkably reduced (P < 0.05), and all were inhibited by intervention with crenolanib or Salidroside (all P < 0.05). No statistically significant difference was observed in the STAT5 phosphorylation ratio between different groups (P > 0.05). Overexpression of STAT3 in the CCSMCs treated with exogenous PDGF-BB and Salidroside significantly decreased the expression of α-SMA (P < 0.05) and increased that of Collagen I (P < 0.05). CONCLUSION: Salidroside could improve the phenotypic transformation of CCSMCs in male rats through the PDGFR/STAT3 signaling pathway, which needs further exploration and verification.

Visualizing the intellectual structure and recent research trends of diabetic retinopathy.

AIM: To analyze the intellectual structure and recent research trends in diabetic retinopathy (DR) and unearth potential knowledge. METHODS: English DR publication included in this study was exported from the Web of Science Core Collection, and Chinese DR publication was exported from China National Knowledge Infrastructure from the establishment time of the database to 2019. CiteSpace and Microsoft Excel were used to visually analyze DR research, including analysis of the number of publications, highly cited publication analysis, spatial distribution analysis, and keyword co-occurrence analysis. RESULTS: A total of 23 795 English studies and 11 577 Chinese studies, including 2089 studies related to traditional Chinese medicine (TCM), were obtained. The data suggested the following: 1) The number of English and Chinese DR publications increased over time, and the growth rate of English publications was relatively fast. 2) The distribution of international scholars and institutions was close, while the distribution was scattered in China. Shanghai Jiao Tong University has the largest number of publications. Tien-Yin Wong was the core author with the largest number of publications. England and the United States are the core of international DR research cooperation. 3) Optical coherence tomography and risk factors are recent international research hot spots and trends. The difference is that TCM is a recent research trend under DR in China. CONCLUSION: DR has drawn an increasing amount of attention worldwide. The focus of research in this field has shifted from tertiary type DR treatment to secondary prevention strategies which focus on the screening and monitoring of disease progression. The advantages of TCM in the prevention of DR have attracted attention, and it is worth incorporating this with Western medicine to address this challenge.

Rare case of brucellosis misdiagnosed as prostate carcinoma with lumbar vertebra metastasis: A case report.

BACKGROUND: Prostatitis caused by Brucella infection is rare and usually lacks typical lower urinary tract symptoms. However, Brucella infection can cause serum prostate-specific antigen levels to become abnormally elevated. When concurrent with lumbar vertebra infection and erosion, brucellosis can easily be misdiagnosed as prostate cancer with bone metastasis. CASE SUMMARY: A 45-year-old man complained of recurrent low back pain and fever for 2 wk. Magnetic resonance imaging of the lumbar vertebrae showed abnormal signs at the rear of the L4-5 vertebral body. Serum prostate-specific antigen level was 17.64 ng/mL, and positron emission tomography/computed tomography suggested the possibility of prostate cancer with liver and lumbar metastases. The patient was transferred to our department for further treatment. He experienced repeated bouts of fever and low back pain during hospitalization. Biopsy results indicated prostatitis. There was no significant increase in white blood cell count or procalcitonin levels. The Mycobacterium tuberculosis smear and antibody detection results were negative. Cefoperazone sulbactam was not effective. Blood culture test results were positive for brucellosis, confirming the diagnosis of brucellosis. After oral anti-infection treatment with doxycycline and rifampicin, the body temperature gradually returned to normal, and lumbago improved. After continuous treatment for 6 mo, the patient recovered. CONCLUSION: In patients with low back pain and fever accompanied by elevated prostate-specific antigen levels and lesions of the prostate and lumbar spine, a detailed medical history and blood and urine cultures should be obtained, and attention should be given to the local epidemic infectious disease situation.

Effects of Qianlie Tongqiao Capsule on Bladder Weight and Growth Factors in Bladder Tissue of Rats with Testosterone-Induced Benign Prostatic Hyperplasia.

Qianlie Tongqiao Capsule (QTC) is clinically confirmed to be efficacious and safe in treating lower urinary tract syndromes and bladder dysfunction that are induced by benign prostatic hyperplasia (BPH). However, the functional mechanisms of QTC remain unclear. We aim to investigate the effects of QTC on both bladder weight and several growth factors in the bladder tissue of rats with testosterone-induced BPH. BPH in the rats was established through bilateral orchiectomy and subcutaneous administration of testosterone propionate (5 mg/kg) dissolved in corn oil. At the end of the study, all bladder tissues were collected and weighed, and a histological examination was conducted using H&E staining. Immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were applied to detect the expression of nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and transformation growth factor-ß1 (TGF-ß1) in the bladder tissue. The expression of Bcl-2 and Bax in the bladder tissue was tested by Western Blot and qRT-PCR. We found that QTC, especially when administered in high-dosages, had a significant inhibitory effect on bladder weight gain and overexpression of NGF, bFGF, and TGF-ß1 in rats with BPH. In addition, QTC downregulated and upregulated protein and mRNA expression of Bcl-2 and Bax in the bladder after prostatic obstruction, respectively. Furthermore, QTC balanced the Bcl-2/Bax ratio. Overall, these results reveal possible functional mechanisms of QTC in treating BPH-caused bladder dysfunction, and further studies are needed.

The Protective Effect of Salidroside on Hypoxia-Induced Corpus Cavernosum Smooth Muscle Cell Phenotypic Transformation.

Salidroside, a major active ingredient isolated from Rhodiola rosea, has a long application in Chinese medical history. It has widely demonstrated effects on fatigue, psychological stress, and depression and exhibits potential antihypoxia activity. Emerging evidence shows that hypoxia is an important independent risk factor for erectile dysfunction (ED). The aim of this study was to clarify the effect of salidroside on hypoxia-induced phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMCs). Our results showed that salidroside decreased the hypoxia-induced expression of collagen and content of vimentin, a corpus cavernosum smooth muscle synthetic protein, in vitro. Simultaneously, salidroside increased expression of the CCSMC contractile proteins, α-smooth muscle actin (α-SMA) and desmin. In vivo, similarly, the expressions of collagen and hypoxia-inducible factor-1α were increased in bilateral cavernous neurectomy (BCN) rats while they were decreased in the salidroside group. Among the phenotypic proteins, α-SMA and desmin increased and vimentin decreased after treating BCN rats with salidroside compared with the BCN alone group. Overall, our results demonstrate that salidroside has the ability to oppose hypoxia and can inhibit the CCSMC phenotypic transformation induced by hypoxia. Salidroside may provide a new treatment method for ED.

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats.

Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.

[Value of non-sexual penile erection for penile rehabilitation in men with erectile dysfunction].

Erectile dysfunction (ED) is a common male disease. Some related studies show that the prevalence of ED is nearly 52% in men aged 40 to 70 years and is increasing among younger males. Hypoxia is now considered to be an independent risk factor for ED and the mechanisms of hypoxia inducing ED are varied and complicated. Recently, an idea in penile rehabilitation has attracted much attention, which aims at improving erectile function by increasing oxygen supply to the cavernosum and reducing tissue fibrosis and apoptosis. The approaches to achieve non-sexual penile erection by increasing oxygen supply to the cavernosum, such as behavior therapy, medication, vacuum constriction device, and intracavernous injection, can simulate normal sexual erection and help patients with penile rehabilitation. This review focuses on the strategies for non-sexual penile erection in penile rehabilitation.

[Maximal Frequent Association Patterns between Symptoms of Coronary Heart Disease Patients with Blood Stasis Syndrome and Medication Constitutions].

A total of 121 medical cases concerning treating coronary heart disease (CHD) pa- tients with blood stasis syndrome (BSS) by Chinese Medicine were collected to establish a database for CHD patients with BSS. By using data mining authors tried to explore inherent laws of its symptoms and medication of Chinese Medicine, and to probe maximal frequent association patterns between its symp- toms and medication constitutions. Of the 121 medical cases, chest pain, chest stiffness, and headache were their common symptoms. Compatibilities of blood-activating drugs, stasis-resolving drugs, and qi- promoting drugs were most commonly used. The association between symptoms and compatibilities con- stituted a most often seen maximal frequent association pattern, which reflected an idea of treating both principal and subordinate symptoms.

Bufalin inhibits pancreatic cancer by inducing cell cycle arrest via the c-Myc/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufalin, a cardiotonic steroid isolated from toad venom (bufo gargarizans Cantor or B. melanotictus Schneider), has widely demonstrated antitumor effects and exhibits potential antitumor activity in various human cancer cells lines. AIMS OF THE STUDY: The main characteristic of cancers including pancreatic cancer is the ability of uncontrolled proliferation. The aim of this study is to clarify the underlying mechanism by which bufalin inhibits pancreatic cancer cell proliferation. MATERIALS AND METHODS: The effect of bufalin on the suppression of tumor growth in vivo was studied in a bioluminescent mouse model generated using the pancreatic cancer cell line BxPC3-luc2 and the cytotoxicity was evaluated in BcPc3 and Sw1990 cells with MTT. Flow cytometry and western blotting analyses were utilized to detect the effect of bufalin on the cell cycle and to detect the cell cycle-related proteins, respectively. Then, a luciferase reporter assay was applied to screen the activity of potent transcription factors following bufalin exposure and their expression was detected by western blotting. RESULTS: Bufalin suppressed tumor growth in a bioluminescence mouse model generated using BxPC3-luc2 cells and inhibited cell proliferation in vitro through inducing cell cycle arrest at S phase. Bufalin treatment inhibited cyclin D1 and cyclin E1 expression and therefore increased expression of p27, a regulatory molecular that controls cell cycle transition from S to G2 phase. Furthermore, luciferase reporter screening studies revealed that bufalin inhibited the expression and activity of the transcription factors c-Myc and NF-κB, which might cause cell cycle arrest at S phase and the inhibition of cell proliferation. CONCLUSIONS: Taken together, our results indicate that bufalin can inhibit pancreatic cancer by targeting c-Myc, thus suggesting that the mechanism of c-Myc regulation by bufalin might be worthy of further study regarding its potential as a therapeutic target for pancreatic cancer treatment.

[Effect of salidroside on the expression of connexin43 in the corpus cavernosum smooth muscle cells of hypoxic rats].

OBJECTIVE: To investigate the effect of salidroside on the expression of the connexin43 (Cx43) protein in the corpus cavernosum smooth muscle cells (CCSMCs) of hypoxic SD rats. METHODS: CCSMCs were cultured in vitro and identified by immunofluorescence staining. The cells were divided into six groups: normal control (21% O2), hypoxia (1% O2), hypoxia+salidroside (HS) 8 µg/ml,HS 16 µg/ml, HS 32 µg/ml, and HS 64 µg/ml, and cultured for 48 hours. Then the relative expression of Cx43 in different groups was detected by Western blot. RESULTS: The in vitro cultured CCSMCs grew well and 90% of the cells showed positivity for α-SMA and desmin on immunohistochemistry. Salidroside ≤64 µg/ml produced no obvious toxicity on the CCSMCs. The expressions of Cx43 and phosphorylated proteins were dramatically increased in the hypoxia group as compared with the normal control (P<0.01 and P<0.05). The HS groups all showed significantly higher expression of Cx43 than the hypoxia group (P<0.01), but the phosphorylation rate of the Cx43 proteins was remarkably decreased (P<0.01). CONCLUSIONS: Hypoxia increases the expression of Cx43 in the CCSMCs of SD rats. Salidroside ≤64 µg/ml cannot reverse the hypoxia-induced change but can reduce the dephosphorylation of Cx43 in CCSMCs. It is deduced that salidroside can protect CCSMCs by decreasing the phosphorylation of Cx43 and suppressing hypoxia-induced formation of the gap junction channel.

[Intracavernosal pressure measurement technology in the animal model of erectile dysfunction].

Penile erection is a primarily aneurovascular event,which depends on the relaxation of the corpus cavernosum smooth muscle cells and engorgement of the penis with blood. The compression of the subtunical venular plexus results in venular blockage.The intracavernosal pressure( ICP) is close to 5-7 mmHg in the flaccid state and rapidly increases to more than 100 mmHg in the tumescence phase. In the study of the animal model of erectile dysfunction,ICP measurement is the golden standard for evaluation of erectile function. In the recent years,telemetric technology has been successfully applied in monitoring the changes of rat ICP abroad,but no such report is seen domestically. This paper presents an overview on the development of the ICP measurement technology.

[Algorithm of double levels of frequency and weight to determine the weight value for syndrome factor differentiation].

Differentiating syndrome factor and forming syndrome type according to symptoms and signs are the rules and processes of syndrome differentiation in traditional Chinese medicine (TCM). TCM syndrome differentiation is a nonlinear complex giant system. In order to solve the key problem of determination of diagnosing weight value for syndrome factor differentiation, a new algorithm of double levels of frequency and weight based on the analysis of frequency statistics was applied, and the accurate syndrome differentiation parameters were acquired. Therefore, based on the nonlinear and multivariate analysis, a new algorithm of calculating diagnostics for syndrome factor differentiation was established.

[Application of Bayesian network in syndrome differentiation system of traditional Chinese medicine].

The concept of syndrome in traditional Chinese medicine (TCM) is a nonlinear, open and complicated huge system. Syndrome differentiation in TCM belongs to cognitive and noetic science. To establish a new syndrome differentiation system based on the key elements of the syndrome is necessary for TCM practitioners to promote differentiation ability and reach consensus on differentiation method. With combination of experience and computation models, the Bayesian network was used in the study of the relationship between the key elements of syndrome and the symptoms, and the relationship among different key elements, in which the computing diagnosis result was identical to the result from an experienced TCM doctor. The study showed that Bayesian network is a good method to deal with the information of symptoms and signs for syndrome differentiation, but it is also not to reflect comprehensively the thinking ability of TCM doctors in doing syndrome differentiation.

[Effect of shuxuetong in preventing restenosis after intracoronary stenting].

OBJECTIVE: To evaluate the effect of shuxuetong (SXT) in preventing restenosis after intracoronary stenting. METHODS: Sixty-eight patients, accepted intracoronary stenting, were divided into two groups, the SXT group and the control group, both of them were treated with conventional treatment, and to the SXT group, SXT was given additionally. The condition of treated coronary artery restenosis in the two groups was compared by way of quantitative coronary angiography and a 6-month follow-up study was adopted. RESULTS: Follow-up study was completed in 43 patients (23 cases in the SXT group, and 20 in the control group). The angina recurrence rate in the SXT group (3 cases, 13%) was significantly lower than that in the control group (7 cases, 35%, P < 0.05). Quantitative coronary angiography showed the restenosis degree of operated artery in the SXT group was significantly milder than that in the control group, with the last lumen losing and index in the SXT group (0.46 +/- 0.25 mm, 24.26 +/- 8.64%) less than those in the control group (0.75 +/- 0.33 mm, 31.25 +/- 11.03%). The net gain lumen and the net gain index in the SXT group (1.23 +/- 0.30 mm, 58.96 +/- 24.68%) were greater than those in the control group (0.98 +/- 0.33 mm, 42.68 +/- 29.51%), all P < 0.05. But the restenosis rate in the two groups was insignificantly different (P > 0.05). CONCLUSION: SXT might has some definite effect in preventing restenosis after intracoronary stenting.