Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis and Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer.@*METHODS@#Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases.@*RESULTS@#A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts.@*CONCLUSIONS@#This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

Identification of immune-related prognostic signature for colon adenocarcinoma based on weighted gene co-expression network analysis / 细胞与分子免疫学杂志

Objective To identify immune-related molecular markers in an attempt to predict prognosis of colon adenocarcinoma (COAD). Methods Immune related genes (IREGs) was analyzed based on the TCGA database. Weighted gene co-expression network analysis (WGCNA) and Cox regression analysis were used to establish risk models. According to the median risk score, COAD patients were divided into high risk and low risk groups. The prognostic difference were compared between the two groups. The function of the model was validated using GEO. Results A total of 1015 IREGs was obtained. The established model consisted of three genes: RAR related orphan receptor C (RORC), leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) and lectin galactoside-binding soluble galectin 4 (LGALS4). The high-risk group had significantly poorer prognosis than low-risk group in the GEO database, and it was validated using a GEO database. Further analysis via univariate and multivariate Cox regression analyses revealed that risk model could function as independent prognostic factor for COAD patients. Conclusion The risk model based on IREGs can predict the prognosis of patients with COAD.

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway / 中国中药杂志

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Chemical constituents in Dolomiaea plants and their pharmacological activities: a review / 中国中药杂志

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.

Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Textual research on Bambusae Concretio Silicea / 中国中药杂志

By studying various ancient texts such as herbal classics and medical literature from different eras, it was found that there were discrepancies in the records about Bambusae Concretio Silicea(Tian Zhu Huang). In order to establish an accurate foundation, this research was based on ancient herbal literature and combined with plant morphology and investigative studies to examine its earliest mentions in ancient texts, nomenclature, medicinal properties, indications, and quality assessment standards. In the early records, Bambusae Concretio Silicea was referred to by several different names, such as "Zhu Huang" "Tian Zhu Huang" "Zhu Gao" "Zhu Tang", and "Zhu Huang". The earliest known formal usage of the name "Tian Zhu Huang" was found in the book Ri Hua-zi's Materia Medica(Ri Hua Zi Ben Cao). Throughout various ancient texts, the earliest recorded information about Bambusae Concretio Silicea also appeared in Ri Hua-zi's Materia Medica, not in Materia Medica of Sichuan(Shu Ben Cao) or other ancient texts. Ri Hua-zi's Materia Medica provided relevant descriptions of its origin, medicinal properties, and indications, albeit with some errors due to limited knowledge. However, this has been a valuable starting point for future research on Bambusae Concretio Silicea and holds pioneering significance in forming a mature system. As the research delved deeper, the medicinal properties of Bambusae Concretio Silicea have been consistent since Ri Hua-zi's Materia Medica, and the understanding has gradually improved through years of clinical verification. During the investigation process, the authors found limited records on the quality evaluation of Bambusae Concretio Silicea in ancient texts. Although the information is scarce, it serves as a foundational basis for establishing corresponding quality grading standards for Bambusae Concretio Silicea in the future.

Regulatory effect of small nuclear ribonucleoprotein-associated protein B on proliferation and metastasis of liver cancer cells / 中华肝脏病杂志

Objective: To study the expression and effect of small nuclear ribonucleoprotein-associated protein B (SNRPB) on proliferation and metastasis of liver cancer tissues and cells. Methods: The bioinformatics database starBase v3.0 and GEPIA were used to analyze the expression of SNRPB in liver cancer tissue and normal liver tissue, as well as the survival and prognosis of liver cancer patients. The expression of SNRPB mRNA and protein in liver cancer cell lines were analyzed by qRT-PCR and Western blot. RNA interference technique (siRNA) was used to determine SNRPB protein expression down-regulation. The proliferation effect on hepatocellular carcinoma cells was observed by MTT assay. Transwell invasion and migration assay was used to detect the changes in the metastatic ability of liver cancer cells after SNRPB down-regulation. Western blot was used to detect the changes of epithelial mesenchymal transition (EMT) markers in liver cancer cells after down-regulation of SNRPB expression. Data were compared between two groups and multiple groups using t-test and analysis of variance. Results: The expression of SNRPB was significantly higher in liver cancer tissue than normal liver tissue, and its expression level was correlated with the prognosis of liver cancer patients. Compared with the immortalized hepatocyte LO(2), the expression of SNRPB was significantly increased in the liver cancer cells (P < 0.01). siRNA-SNRPB had significantly inhibited the expression of SNRPB mRNA and protein in liver cancer cells. MTT results showed that the absorbance value was lower in SNRPB knockdown group than negative control group, and the difference at 96 h after transfection was most significant (P < 0.01). Transwell assay results showed that compared with the negative control group, the SNRPB knockdown group (MHCC-97H: 121.27 ± 8.12 vs. 46.38 ± 7.54; Huh7: 126.50 ± 6.98 vs. 41.10 ± 8.01) invasion and migration (MHCC-97H: 125.20 ± 4.77 vs. 43.18 ± 7.32; Huh7: 132.22 ± 8.21 vs. 38.00 ± 6.78) ability was significantly reduced (P < 0.01) in liver cancer cells. Western blot showed that the expression level of epithelial phenotype marker E-cadherin was decreased after down-regulation of SNRPB, while the expression levels of mesenchymal phenotype markers N-cadherin and vimentin was increased, suggesting that down-regulation of SNRPB inhibited EMT in liver cancer cells. Conclusion: SNRPB expression is significantly increased in liver cancer tissues and cells, and it is involved in regulating the proliferation, metastasis and EMT of liver cancer cells.

THBS4 Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inducing M2 Polarization of Tumor-associated Macrophages / 中国生物化学与分子生物学报

Thrombospondin 4 (THBS4), a member of the THBS family, is a protein secreted by the extracellular matrix and is involved in regulating various physiological processes, such as cell proliferation, adhesion and angiogenesis. Recent studies have shown that the inflammation stimulates THBS4 production and induces the adhesion and accumulation of macrophages. Our previous study confirmed that THBS4 acts as an oncogene in hepatocellular carcinoma (HCC), the effect of THBS4 on the immune microenvironment of HCC remains unclear. This study aims to analyze the role of THBS4 in promoting the metastasis of HCC cells by inducing M2-type polarization of tumor-associated macrophages. We simulate the tumor microenvironment through HCC conditioned medium (HCM) and found that the expression of THBS4 in macrophages increased in a time-dependent manner under the action of HCM (P<0.05); THBS4 knockdown promotes the expression of M1 macrophages markers IL-1β and CD86 (P<0.01), while the expression of M2-type markers IL-10 and CD206 were decreased (P<0.01). Transwell co-culture assay was used to further detect the effect of THBS4-induced M2-type macrophages on HCC metastasis. Results from co-culture of THBS4-downregulated M2 macrophages with HepG2 cells showed that THBS4-downregulated M2-TAMs significantly inhibited the invasion and migration ability of HepG2 cells (all P < 0.01). In conclusion, the tumor microenvironment promotes the expression of THBS4 in macrophages, and THBS4 may promote the invasion and metastasis of HCC cells by inducing M2-type polarization of macrophages. This study provides some new experimental basis for exploring the establishment of THBS4-induced HCC immune microenvironment.

Di'ao Xinxuekang alleviates non-alcoholic steatohepatitis in mice by up-regulating Nrf2/HO-1 signaling pathway / 中国中药杂志

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1β, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.

Baicalin inhibits LPS/IFN-γ-induced inflammation via TREM2/TLR4/NF-κB pathway in BV2 cells / 中国中药杂志

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.

Application of metabonomics in study of traditional Chinese medicine syndrome:a review / 中国中药杂志

Syndrome is a nonlinear "internal-excess external-deficiency", "dynamic spatial-temporal" and "multi-dimensional" complex system and thus only by using a versatile method can the connotation be expounded. Metabonomics, which is dynamic, holistic, and systematic, is consistent with the overall mode of traditional Chinese medicine(TCM)(holistic view and syndrome differentiation and treatment). Therefore, metabonomics is very important for the research on the differentiation, material basis, and metabolic pathways of syndromes, and efficacy on syndromes. This study reviewed the application of metabonomics in the study of TCM syndromes in recent years, which is expected to objectify the research on TCM syndromes.

Clinical analysis of ultrasound negative pressure suction with percutaneous nephroscope in the treatment of perirenal abscess / 中华泌尿外科杂志

Objective:To evaluate the clinical efficacy and safety of ultrasound negative pressure suction with percutaneous nephroscope in the treatment of perirenal abscess.Methods:The clinical data of 11 patients with perirenal abscess admitted to Zhejiang Provincial People's Hospital from January 2013 to February 2021 were retrospectively analyzed. There were 4 males and 7 females. The average age was 59(51-76) years. The abscess was located on the left side in 4 cases and on the right side in 7 cases. The average diameter of abscess was 11.2(8.1-19.2) cm. All patients had fever, low back pain and abdominal mass, accompanied by bladder irritation in 6 cases, gross hematuria in 5 cases, abdominal distension, nausea and anorexia in 3 cases. There were 7 cases with type 2 diabetes, 2 cases with rheumatoid arthritis and 6 cases with ipsilateral kidney and ureter stone. Among the 11 patients, 6 had a history of urinary tract infection, 1 had a history of upper respiratory tract infection, 1 had secondary infection of perirenal hematoma after traumatic renal rupture, and 3 had secondary infection of perirenal hematoma after percutaneous nephroscopy. All patients were treated with ultrasound negative pressure suction with percutaneous nephroscope under local anesthesia by single operator. The operation time, intraoperative blood loss, drainage volume, drainage tube indwelling time, postoperative body temperature returned to normal time, postoperative hospital stay, therapeutic effect and complications were analyzed.Results:All operation procedures of 11 patients were successfully completed, including 8 cases of single channel, 2 cases of double channels and 1 case of three channels. The average operation time was 44(20-74)min, the average amount of blood loss was 15(10-20)ml, the average amount of pus was 325(200-500)ml, the average indwelling time of drainage tube was 8(6-12)d, the average time of body temperature returned to normal was 0.9(0.5-2.0)d, and the average hospitalization time was 9.6(7.0-14.0)d. Before discharge, CT reexamination showed that the perirenal abscess disappeared. There were no serious complications during and after operation. The average follow-up time was 4.4(3-8) months. There was no recurrence in all patients.Conclusions:Ultrasound negative pressure suction with percutaneous nephroscope is one of the safe and effective surgical methods for the treatment of perirenal abscess. It has the advantages of small trauma, quick recovery, complete drainage, exact effect and fewer complications.

The efficacy and safety of green laser enucleation of prostate with end-fire fiber in treating benign prostatic hyperplasia / 中华泌尿外科杂志

Objective:To investigate the efficacy and safety of green laser vaporization enucleation of the prostate with end-fire fiber in the treatment of benign prostatic hyperplasia.Methods:The clinical data of 218 patients with benign prostatic hyperplasia admitted to Zhejiang Provincial People's Hospital from August 2018 to July 2019 were retrospectively analyzed. All 218 patients presented symptoms of varying degrees of frequent voiding, urgency, nocturia, and progressive dysuria, with age of(76.2±8.4) years, prostate volume of(77.3±21.6) ml, and preoperative PSA of (3.5±0.9)ng/ml, preoperative maximum urine flow rate (Qmax)of(7.9±1.8)ml/s, residual urine volume of(82.3±26.3)ml, quality of life score(QOL) of(4.9±1.1)points, and International Prostate Symptom Score (IPSS) of (25.4±7.6) points. Lithotomy position was used intraoperatively, and intravenous combined general anesthesia or intraspinal anesthesia was performed before the green laser vaporization enucleation of the prostate. Intraoperatively, green laser equipment used a vaporization power of 80W, an optical fiber with a end-fire fiber of 800μm in diameter, and hemostasis power of 20W. The surgical procedure was firstly to vaporize and cut 3 grooves from the bladder neck to the ejaculatory hole plane of the prostate at 5, 7 and 12 o'clock, reaching deep enough to expose the surgical capsule, in order to set up" three lines and one side" anatomical landmarks. A combination of sheath peeling and vaporization cutting along the envelope layer was used to enucleate the hyperplastic glands according to the " three-leaf " method. After enucleation, the tissue was pushed into the bladder, and the enucleated tissue was crushed and aspirated with a tissue morcellation. Perioperative and postoperative parameters including vaporized enucleation time, tissue morcellation time, hemoglobin changes, bladder irrigating time, indwelling catheterization time, postoperative hospital stay, postoperative Qmax, residual urine volume, postoperative complications, IPSS and QOL were recorded. Urgency with involuntary urine leakage was diagnosed as urge incontinence, involuntary urine leakage after coughing was diagnosed as stress urinary incontinence, and the incontinence degree was defined according to the amount of pad used, with mild of 1-2 pads/day, moderate of 3-4 pads/day, and severe of 5 or more pads/day.Result:All 218 operations were successfully completed. Capsule perforation occurred in 8 cases(3.7%), and there was no bladder perforation. The time of vaporization and enucleation was (42.5±8.3)min, and the time of tissue morcellation was(12.1±3.4)min. The intraoperative and postoperative hemoglobin loss was(4.7±1.3)g/L, and there were no blood transfusion or re-operation for stopping bleeding. The average bladder irrigation time after operation was(6.3±1.6)h, the average indwelling catheterization time was(1.2±0.2)days, and the average postoperative hospital stay was (2.2±0.7)days. The Qmax 1 month after operation was(18.5±4.8) ml/s, and the residual urine volume of the bladder was(6.4±1.9)ml, which showed a statistical difference compared with the preoperative parameters( P<0.01). In addition, the QOL(2.1±0.4) and IPSS(7.1±2.1)showed a statistical difference at 3 months follow-up, compared with the parameters before or 1 month after the operation( P<0.01). The volume of the prostate at 3 months after the operation was(34.6±6.3) ml, and the PSA was(2.4± 0.5) ng/ml, which was statistically different from the preoperative corresponding parameters( P<0.01). During the follow-up within one year, 11 cases were detected incontinence during the 1-month follow up, including 6 cases of urge incontinence. After drug treatment, good continence achieved 3 months after the operation. The other 5 cases had stress urinary incontinence, 3 of whom got good continence after the drugs treatment and pelvic floor muscle exercise, and two patients recovered to one pad per day. A total of 24 cases of urethral stricture were found during the 12-month follow-up, including 16 cases of anterior urethral stricture, which was treated with 3 months of regular urethral dilation. Another 8 cases had bladder neck contracture, and were treated by bladder neck resection and regular urethral dilatation. All of them did not recur 6 months after the procedure. Conclusions:The end-fire green laser vaporization enucleation of the prostate has the advantages of short operation time, less intraoperative bleeding, and obvious improvement in postoperative symptom scores. The short-term effect is obvious, and the long-term effect still needs further study to confirm.

Differences in the diagnosis of prostate cancer by image fusion targeted biopsy, systematic biopsy and combined biopsy / 中华泌尿外科杂志

Objective:To explore the detection rate of prostate cancer and clinically significant prostate cancer (CsPCa) in three puncture methods: targeted biopsy fusion with MRI and ultrasound imaging, system puncture, and combined puncture.Methods:The clinical data of 164 patients who underwent both targeted biopsy and systematic biopsy in Zhejiang Provincial People's Hospital from April 2019 to April 2020 were retrospectively analyzed. The median age was 67(33-90)years. Preoperative serum tPSA was 8.97(0.64-95.63)ng/ml and fPSA was 1.31(0.29-9.25)ng/ml. There were 96 patients result in tPSA<10 ng/ml, 65 and 3 patients result in 10≤tPSA<50 ng/ml and tPSA≥50 ng/ml. The prostate volume was 34.9(11.6-152.0) cm 3. According to result of PI-RADS score, there were 42 patients got 3 points and 66, 56 patients got 4 and 5 points respectively in PI-RADS score of suspicious nodules. First, a targeted puncture (targeted biopsy) was performed on the suspected lesions by fusion imaging of magnetic resonance and ultrasound. Then 12-needle systematic prostate biopsy was performed under the guidance of ultrasound. Those two methods performed together was called combined biopsy. This study compared the detection rates of prostate cancer and CsPCa among the three popular methods in all cases, different PI-RADS cases, and different tPSA cases. Results:In this study, patients was detected as positive result in 126 of 164 patients. The detection rates of prostate cancer in targeted biopsy and systematic biopsy were 66.46%(109/164) and 64.02%(105/164), respectively, the result reveals no statistical significance ( P=0.64). In contrast, the positive rate of combined biopsy [76.83%(126/164)] was higher than targeted biopsy ( P=0.04) and systematic biopsy ( P=0.01), and the difference was statistically significant. In the detection rate of CsPCa, the positive detection rates of targeted biopsy group, systematic biopsy group and combined biopsy group were 50.61%(83/164), 45.12%(90/164) and 54.88% (126/164), respectively. Moreover, there was no significant statistical significance among the three groups ( P>0.05). Group comparison was analyzed according to PI-RADS score. In PI-RADS 4 group and PI-RADS 5 group, combined biopsy was[90.91%(60/66), 100.00%(56/56)] and systematic biopsy was [71.21%(47/66), 87.50%(49/56)] which reveals significant difference in prostate cancer detection rates ( P=0.00, P=0.01). In PI-RADS 4-5 groups, the detection rate of prostate cancer by targeted biopsy [86.89%(106/122)] was significantly higher than systematic biopsy [78.69%(96/122), P=0.01], but still lower than that by combined biopsy [95.08%(116/122), P=0.03]. The CsPCa detection rates of PI-RADS 3 group targeted biopsy, systematic biopsy and combined biopsy were 2.38%(1/42), 7.14%(3/42) and 7.14%(3/42), respectively. There were 59.09%(39/66), 46.97%(31/66) and 62.12%(41/66) in PI-RADS 4 groups, respectively; There were 78.57%(44/56), 71.43%(40/56) and 82.14%(46/66) in PI-RADS 5 groups, respectively, with no statistical significance ( P>0.05). However, in PI-RADS 4-5 groups, the CsPCa detection rate of combined biopsy [71.31%(87/122)] was higher than that of systematic biopsy [58.20%(71/122)], with statistical significance ( P=0.03). In the tPSA<10 ng/ml group, the prostate cancer detection rate of combined biopsy[72.92%(70/96)] was higher than that of systematic biopsy[59.38%(57/96)], and the difference was statistically significant ( P<0.05). There was no significant difference between the detection rate of targeted biopsy[61.43%(59/96)]and combined biopsy ( P=0.09). In the group of 10ng/ml≤tPSA<50ng/ml, the prostate cancer detection rates of targeted biopsy, systematic biopsy and combined biopsy were 72.31%(47/65), 69.23%(45/65) and 81.54%(53/65), respectively, and there was no statistical significance ( P>0.05). In tPSA≥50 ng/ml group, the prostate cancer detection rate of the three biopsy methods was 100.00% (3/3), and there was no statistical significance ( P>0.05). Conclusion:For patients with highly suspected prostate cancer on multiparameter MRI(PI-RADS 4-5) or tPSA<10 ng/ml, combined biopsy was an appropriate method to diagnose the prostate cancer.

Effects of total flavonoids of Rhododendra simsii on ameliorating brain injury via G protein-coupled SOCE pathway mediated by STIM and Orai in subacute phase of ischemia/reperfusion / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii (TFR) on improving cerebral ischemia/reperfusion injury (CIRI) and its relationship with STIM/Orai-regulated operational Ca2+influx (SOCE) pathway. METHODS Oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cells were used to simulate CIRI in vitro, and the intracellular Ca2+ concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry, respectively. The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/Orai gene overexpression. The CIRI model was established by MCAO in SD rats. The activities of inflammatory cyto?kines IL-1, IL-6 and TNF-αin serum were detected by ELISA. The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining. The protein and mRNA expression levels of STIM1, STIM2, Orai1, caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR, respectively. RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca2+ and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group, and this trend was enhanced by SOCE antagonist 2-APB. STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca2+overload in OGD/R model, while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload. In the in vivo experiment, TFR significantly reduced the brain histopathological damage, infarction of brain tissue, the contents of IL-1, IL-6 and TNF-α in the serum in MCAO rats and down-regulated the expression of STIM1, STIM2, Orai1 and caspase-3 protein and mRNA in the brain tissue, and up-regulated the expression of PKB. The above effects were enhanced by the addition of 2-APB. CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis, decrease Ca2+ overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and Orai, suggesting that it has a protective effect against subacute CIRI.

Analysis of Neuroprotective Effect of Danggui Shaoyaosan on APPswe/PS1ΔE9 Transgenic Mice Based on Circular RNA Sequencing / 中国实验方剂学杂志

Objective:To investigate the neuroprotective effects of Danggui Shaoyaosan （DSS） on APP_swe/PS1_ΔE9transgenic （APP/PS1） mice and its mechanism related to circular RNA （circRNA）. Method:Totally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group， and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline， and DSS group received drug by gavage administration， all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B1 （Akt1）， p-Akt1， B lymphocytoma-2 （Bcl-2）， and Bcl-2-Associated X protein （Bax） in the hippocampus were detected by immunoblotting （Western blot）. The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method. Result:Compared with the model group， there were 90 differentially expressed circRNA after intervention with DSS， of which 46 were up-regulated and 44 down-regulated. Compared with the normal group， the expression levels of circRNA1398 and circRNA1399 in the model group decreased， and the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p increased. Compared with the model group， the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated， while the expression levels of miR-103-3p， miR-153-3p， miR-143-3p， and miR-143-5p were down-regulated. Compared with the normal group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the model group decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）， and the expression of Bax and Caspase in the model group increased （<italic>P</italic><0.01）. Compared with the model group， the expression of p-PI3K， Akt1， p-Akt1， and Bcl-2 in the hippocampus of the DSS group increased （<italic>P</italic><0.01）， and the protein expression of Bax and Caspase decreased （<italic>P</italic><0.01）. Compared with the normal group， the apoptosis level in the hippocampus of the model group increased， with an apoptosis rate of （43.76±2.92）%. Compared with the model group， the apoptosis rate of DSS group was （24.64±3.39）%. Conclusion:DSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice， and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.

Investigation on Anti-atherosclerosis Mechanism of Di'ao Xinxuekang Based on NLRP3 Inflammasome / 中国实验方剂学杂志

Objective:To investigate the effects of Di'ao Xinxuekang （DXXK） on NLRP3 inflammasome in mouse RAW264.7 macrophages and thoracic aorta of rats with atherosclerosis （AS）， so as to explore its anti-AS mechanism. Method:RAW264.7 cells were stimulated with oxidized low density lipoprotein （ox-LDL） and then intervened with MCC950 and DXXK. The contents of tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） were determined by enzyme linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of Nod-like receptor protein 3 （NLRP3）， inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD （ASC）， and cysteine-dependent aspartate-directed protease-1 （Caspase-1） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blotting. Sixty male SD rats were randomly divided into the normal group， model group， atorvastatin group （2.0 mg·kg^-1）， as well as high-， medium-， and low-dose （100， 30， and 10 mg·kg^-1） DXKK groups， with 10 rats in each group. The rats were exposed to the high-fat diet and vitamin D₂ for inducing AS. The blood lipid level was measured using an automatic biochemical analyzer， followed by the calculation of AS index （AI）. The contents of serum TNF-<italic>α</italic> and IL-1<italic>β</italic> were determined by ELISA， and the mRNA and protein expression levels of NLRP3， ASC， and Caspase-1 in thoracic aorta were assayed by Real-time PCR and Western blotting. HE staining and Sirius red staining were conducted to observe the pathomorphological changes in the abdominal aorta and aortic sinus. Result:Compared with the normal group， the model group exhibited significantly increased TNF-<italic>α</italic> and IL-1<italic>β</italic> contents and up-regulated NLRP3， ASC， and Caspase-1 mRNA and protein expression in RAW264.7 cells （<italic>P</italic><0.01）. The above indexes in each drug administration group were significantly reduced in contrast to those in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. The comparison with the model group showed that cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and AI in each DXXK group significantly declined， while the high-density lipoprotein cholesterol （HDL-C） was significantly elevated （<italic>P</italic><0.05， <italic>P</italic><0.01）. The levels of serum TNF-<italic>α</italic> and IL-1<italic>β</italic> and the mRNA and protein expression levels of NLRP3， ASC， and Caspase-1 in the thoracic aorta were decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Abdominal aortic lesions and fibrous hyperplasia of aortic sinus were significantly improved. Conclusion:DXXK has a significant anti-AS effect， which is possibly related to the inhibition of NLRP3 inflammasome.

Danggui Shaoyaosan Inhibits Neuroinflammation in AD Rats by Regulating NLRP3/Caspase-1 Pathway / 中国实验方剂学杂志

Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan （DSS） in a rat model of amyloid-<italic>β</italic>-peptide_1-42 （A<italic>β</italic>_1-42）-induced Alzheimer's disease （AD） as well as its regulatory effect on NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1） signaling pathway. Method:The AD animal model was established via intracerebral injection of A<italic>β</italic>_1-42 and treated with different concentrations of DSS after the division of rats into the sham operation group， model group， as well as the high-， medium-， and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin （HE） staining and Golgi staining， followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin （IL）-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β </italic>were assayed by Western blot. Result:Compared with the sham operation group， the model group exhibited significantly decreased learning and memory abilities （<italic>P</italic><0.01）， impaired neuronal morphology and function， up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression， enhanced NLRP3 inflammasome activation， and elevated NLRP3， Caspase-1， and IL-1<italic>β</italic> protein expression （<italic>P</italic><0.01）. Compared with the model group， DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats （<italic>P</italic><0.05， <italic>P</italic><0.01）， restored neuronal morphology and function， down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18， reduced the activation of NLRP3 inflammasomes， and lowered the protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> （<italic>P</italic><0.01）. Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway， thus exerting the neuroprotective effect.