Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. METHODS: A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-ß)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. RESULTS: The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-ß-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. CONCLUSION: This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

Study on the Consistency Between Automatic Measurement Based on Convolutional Neural Network Technology and Manual Visual Evaluation in Intracavitary Ultrasonic Cine of Anterior Pelvic.

OBJECTIVES: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. METHODS: A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid-axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10-50 mL, 50-100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman graph. RESULTS: Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland-Altman plot shows the proportion of samples outside the limit was below 5%. CONCLUSIONS: CNN-based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Generation of induced pluripotent stem cells from Bornean orangutans.

Introduction: Orangutans, classified under the Pongo genus, are an endangered non-human primate (NHP) species. Derivation of induced pluripotent stem cells (iPSCs) represents a promising avenue for conserving the genetic resources of these animals. Earlier studies focused on deriving orangutan iPSCs (o-iPSCs) from Sumatran orangutans (Pongo abelii). To date, no reports specifically target the other Critically Endangered species in the Pongo genus, the Bornean orangutans (Pongo pygmaeus). Methods: Using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells to generate iPSCs (bo-iPSCs) from a female captive Bornean orangutan. In this study, we evaluate the colony morphology, pluripotent markers, X chromosome activation status, and transcriptomic profile of the bo-iPSCs to demonstrate the pluripotency of iPSCs from Bornean orangutans. Results: The bo-iPSCs were successfully derived from Bornean orangutans, using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells. When a modified 4i/L/A (m4i/L/A) culture system was applied to activate the WNT signaling pathway in these bo-iPSCs, the derived cells (m-bo-iPSCs) manifested characteristics akin to human naive pluripotent stem cells, including high expression levels of KLF17, DNMT3L, and DPPA3/5, as well as the X chromosome reactivation. Comparative RNA-seq analysis positioned the m-bo-iPSCs between human naive and formative pluripotent states. Furthermore, the m-bo-iPSCs express differentiation capacity into all three germlines, evidenced by controlled in vitro embryoid body formation assay. Discussion: Our work establishes a novel approach to preserve the genetic diversity of endangered Bornean orangutans while offering insights into primate stem cell pluripotency. In the future, derivation of the primordial germ cell-like cells (PGCLCs) from m-bo-iPSCs is needed to demonstrate the further specific application in species preservation and broaden the knowledge of primordial germ cell specification across species.

Effects and mechanism of Elafibranor on the proliferation, migration and apoptosis of human prostate cancer / 现代泌尿外科杂志

【Objective】 To investigate the effects and molecular mechanism of Elafibranor (ELA) on the proliferation, migration and apoptosis of human prostate cancer (PCa) cells. 【Methods】 After PCa DU145 cells were treated with culture media containing different dosages of ELA, the proliferation, migration and apoptosis were determined with MTT assay, wound healing assay and Transwell assay, respectively. The expressions of genes related to lipid metabolism were detected with real-time quantitative polymerase chain reaction (real-time qPCR). 【Results】 The relative cell proliferation rate at 48 h was 100% in the blank control group, (86.9±7.8)% in the low-dose (5 μmol/L) group and (58.5±9.4)% in the high-dose (15 μmol/L) group;the wound healing rate at 24 h was (74.7±3.2)%, (61.8±2.9)% and (53.2±3.3)%;the relative percentage of migrated cells at 24 h was 100%, (32.4±11.2)% and (15.4±3.2)%;the cell apoptosis rate at 48 h was (9.3±1.4)%, (11.3±0.3)%, and (15.2±4.5)%, respectively, all P<0.05. After ELA treatment for 48 h, the genes related to fatty acid intake (SCPX, PLTP) and fatty acid oxidation (PDK1, ACOX2) were significantly down-regulated in the high-dose group, while the gene related to fatty acid deposition (PLIN2) was significantly up-regulated, indicating that the lipid metabolism pathway of DU145 cells was seriously interfered by the ELA treatment. 【Conclusion】 ELA can inhibit the proliferation and migration, and promote the apoptosis of prostate cancer cells by interfering in the lipid metabolism pathway, which exhibits remarkable potential of clinical translation in the field of anti-tumor chemotherapy.

Preoperative interventional embolization for intracranial hypervascular tumors / 中华神经医学杂志

Objective:To investigate the therapeutic value of interventional embolization on feeding artery in intracranial hypervascular tumors.Methods:Forty-five patients with intracranial hypervascular tumors, admitted to and accepted interventional embolization of the feeding artery before craniotomy in Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from March 2019 to August 2022, were chosen; a retrospective analysis was performed on the clinical data of these patients. The imaging characteristics, pathological types, preoperative embolization indications, embolization effects and embolism-related complications were summarized to evaluate the safety and effecacy of preoperative interventional embolization.Results:Among the 45 patients, 21 patients had hemangioblastomas, 15 had meningiomas, 5 had hemangiopericytomas, and 4 had glomus jugular tumors. The technical success rate of interventional embolization was 97.8% (44/45); in this frustrated case, the middle meningeal artery was too circuitous for microcatheter to pass. Among the successful ones, 41 patients used liquid embolism agent onyx and 3 patients applied liquid embolism agent NBCA. Seven, 26 and the rest 11 patients achieved complete embolization, sub-total embolization and partial embolization, respectively. Four patients had embolism-related complications, including 2 with rupture of middle meningeal arteries, 1 with Marathon catheter failed to be pulled out, and 1 with functional glomus jugular tumor having pheochromocytoma crisis; these 4 patients were treated timely without serious complications.Conclusion:For intracranial hypervascular tumors, preoperative interventional embolization is safe and effective; it is necessary to master embolization indications and select appropriate embolization methods and materials.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Multiscale low-rank plus sparsity modeling in fast ultra-high-field cerebrovascular 4D Flow imaging / 中华放射学杂志

Objective:To investigate the application of multiscale low-rank plus sparsity (MLRS) modeling in fast ultra-high-field intracranial 4D Flow imaging.Methods:Ten healthy volunteers, 5 males and 5 females, aged 23-35 (29±4) years old, recruited from October 2022 to January 2023 at Huashan Hospital of Fudan University, were prospectively collected. A MLRS model acceleration algorithm was proposed according to the characteristics of 4D Flow data based on the multiscale low-rank (MLR) model. Firstly, full sampling brain 4D Flow scans were performed on healthy volunteers using 7.0 T MR, and the acquired data were under-sampled with Gaussian distributions at different acceleration rates (R of 4, 8, 12, and 16, respectively). The root mean square error (RMSE) and peak signal-to-noise ratio (PSNR) of the compressed sensing algorithm (CS), low-rank plus sparse algorithm (L+S), MLR, and MLRS model were calculated at different acceleration rates, with fully sampled data as reference. And the comparison of models was performed using the paired-samples t-test or Wilcoxon signed rank test. Pearson′s test was used to assess the correlation between hemodynamic parameters of the 4 algorithms and the fully sampled reference values at different acceleration rates, and the correlation coefficients were compared using Wilcoxon signed rank test. Results:The RMSE under the same acceleration rates was MLRS, MLR, L+S, and CS models in ascending order, and the RMSE of the MLRS model was significantly lower than that of the MLR, L+S, and CS models ( P<0.05); the PSNR was MLRS, MLR, L+S, and CS models in descending order, and the PSNR of the MLRS model was significantly higher than that of the MLR, L+S, and CS model ( P<0.05). The correlation coefficients between the blood flow velocity measured by the MLRS model and the reference value were significantly higher than those of the MLR, L+S, and CS models for different acceleration rates ( P<0.05). Conclusion:The proposed MLRS algorithm is capable of accelerating ultra-high-field 4D Flow MR imaging of the brain while guaranteeing the image quality, and the MLRS model has higher reconstruction accuracy compared with conventional acceleration models at the same acceleration rate.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Anatomy of endoscopic odontoidectomy via submandibular approach / 解剖学报

Objective To provide the basis for endoscopic craniocervical junction surgery through cervical CT image and endoscopic odontoid process anatomy of atlas, axis and odontoid. Methods A total of 150 cases of cervical vertebrae were selected for high resolution thin slice plain CT measurement to evaluate the atlantoaxial structure and its adjacent structure, and to estimate the safe boundary of odontoid process resection. The atlantoaxial odontoid process was anatomized on 3 cadaver head specimens under endoscope through the submandibular approach using STORZ endoscopy system and endoscopic surgical instruments. Results The average length of atlas anterior arch and other anatomical marks were measured by CT, and the safety boundary area of odontoidectomy was estimated to be（240.9 ± 39.92）mm~2, male:（248.3 ± 49.64）mm~2, Female:（233.2 ± 24.54）mm~2. Through the submandibular endoscopic approach, the atlantoaxial anatomy and odontoidectomy anatomy made a transverse incision at the midpoint of the connecting line between one mandibular angle and hyoid bone to expose the submandibular triangle area. Under the endoscope, the digastric muscle and the greater angle of hyoid bone were exposed through the submandibular triangle area, and the retropharyngeal space was passively separated layer by layer to the prevertebral space to expose the prevertebral fascia. After removing the prevertebral tissue, the atlas, the dentate process of the axis, the atlantooccipital joint, the atlantoaxial joint, and part of the foramen magnum were fully exposed. Conclusion Estimating odontoid resection safety boundary area by CT image, in combination with endoscopic odontoidectomy anatomy via sunbmandibular approach, we can perform the surgery safely and efficiently under the bright of endoscope with surgical instruments, which can significantly reduce the incidence of cerebrospinal fluid leakage and postoperative infection while decompressing.

Changes of serum sex hormones, 25 (OH) D3 levels, islet function and their internal relationship in patients with gestational diabetes / 中华内分泌外科杂志

Objective:To investigate the changes of serum sex hormones, 25-hydroxyvitamin D3, 25 (OH) D3] levels and islet function in patients with gestational diabetes mdlitus (GDM) , and to analyze their intrinsic relationships.Methods:50 GDM patients admitted to the Department of Clinical Medicine of Wuhan Traditional Chinese Medicine Hospital from Mar. 2018 to Sep. 2019 were selected as the study group, and 50 healthy pregnant women were selected as the control group. Serum level of sex hormones, 25 (OH) D3 level, islet function [Fasting insulin (FINS) , Insulin resistance index (HOMA-IR) , Islet β cell function index (HOMA-β) ], the correlations between serum sex hormones, 25 (OH) D3 levels, and islet function changes were analyzed using Person, and the influencing factors of GDM were analyzed using binary logistic.Results:The estrogen level, progesterone level, FINS level and HOMA-IR of the observation group were significantly higher than those of the control group[ (6525.28±2095.51) vs (2259.02±717.75) pg/ml, (554.34±32.85) vs (385.34±24.59) ng/ml, (12.69±3.93) vs (9.68±3.19) mU/L, (3.06±1.06) vs (2.01±0.63) ]. 25 (OH) D3 and HOMA-β in the observation group were significantly lower than those in the control group[ (17.46±5.59) vs (21.51±7.14) ng/ml, (137.31±32.11) vs (281.76±54.02) ], the differences were statistically significant ( P<0.05) . According to Pearson analysis, sex hormones were positively correlated with FINS and HOMA-IR ( P<0.05) and negatively correlated with HOMA-β ( P<0.05) ; 25 (OH) D3 was positively correlated with HOMA-β ( P<0.05) and progestin was negatively correlated ( P<0.05) ; FINS was positively correlated with HOMA-IR ( P<0.05) , and HOMA-IR was negatively correlated with HOMA-β ( P<0.05) . 25 (OH) D3 and HOMA-β were risk factors for GDM ( P<0.05) , and FINS and HOMA-IR were protective factors for GDM ( P<0.05) . Conclusions:GDM patients have higher levels of sex hormones, lower levels of25 (OH) D3, HOMA-β, vitamin D deficiency or deficiency, and decreased insulin secretion. There is a correlation between 25 (OH) D3 and HOMA-β.

Advance in Flexible Variable Stiffness Actuator of Rehabilitation Robot (review) / 中国康复理论与实践

Flexible variable stiffness actuator is divided into four categories including elastic element, pneumatic element, electric-magnetic element and intelligent material. It is gradually applied in rehabilitation robot. It could adapt the change of patient's impedance in the upper and lower limb rehabilitation robots, ensure the safety of the wearer in the exoskeleton, and improve the biomimetics in the prosthesis. Variable stiffness driving mechanism for rehabilitation robot still has some disadvantages. It is proposed to have compact structure, low power consumption, good stiffness characteristics, high response rate and progressive output torque curve, etc.

Follow-up and further intervention for postoperative pulmonary venous obstruction of total anomalous pulmonary venous connection / 中华胸心血管外科杂志

Objective:Postoperative venous obstruction (PVO) is the most severe complication of total anomalous pulmonary venous connection (TAPVC), and facing challenging re-intervention with high mortality. We aimed to review and analyze the follow-up and management of postoperative PVO in our center.Methods:We conducted a retrospective study of the patients with isolated TAPVC admitted in our center from October 2013 to October 2019. All available data and images of PVO patients were reviewed, such as the initial perioperative medical records, patients’ follow-up records, results of patients’ echo and CT angiography. Re-intervention including hybrid technique, sutureless technique, and patch augmentation, were carried out for postoperative PVO patients. The results were reviewed and analyzed to find the risk factors for adverse prognosis.Results:A series of 174 isolated TAPVC patients were admitted in our center and 169 received surgical treatment and 26 (26/169, 15.4%) had postoperative PVO. The diagnosis was made at a median time of 11.5 (0-77) weeks after initial operation and within 6 months of surgery in 22 (22/26, 84.6%) of the 26 patients. The subtype of TAPVC patients with postoperative PVO were: supracardiac 11 cases (11/26, 42.3%), cardiac 7 cases (7/26, 26.9%), infracardiac 5 cases (5/26, 19.2%), and mixed 3 cases (3/26, 11.5%). Bilateral obstruction and stenosis with diffusely small pulmonary veins were in 12 (12/26, 46.2%) and 3 cases (3/26, 11.5%) respectively. PVO progressed to worse condition in all the 26 cases during follow-up period. 8 (8/26, 30.8%) postoperative PVO patients underwent 10 re-interventions: one cases had 3 re-interventions. Five-year survival for patients with postoperative PVO was worse than those without postoperative PVO ( HR=6.46, 95% CI: 2.34-17.85, P<0.01). Risk factors for death or re-intervention in postoperative PVO patients were earlier presentation after TAPVC repair ( HR=0.85, 95% CI: 0.73-0.99, P=0.04) and an increased number of lung segments affected by obstruction ( HR=1.74, 95% CI: 1.01-2.99, P=0.04). Conclusion:Risk factors for death or re-intervention in postoperative PVO patients were earlier presentation after TAPVC repair and an increased number of lung segments affected, which should be focused on during strict follow-up period. Early re-intervention should be taken before irreversible secondary changes occur in these patients.

Effect of Drought Stress on Growth and Photosynthetic Physiological Parameters of Acanthopanax senticosus / 中国实验方剂学杂志

Objective:To study the effects of different drought conditions on the growth and photosynthetic physiological parameters of Acanthopanax senticosus，in order to provide the theoretical basis for standardized planting and rational development and utilization of A. senticosus. Method:In this study，three-year-old A. senticosus was used as experimental samples. The growth parameters，photosynthetic parameters，and photosynthetic physiological parameters were determined to study the effects of different drought conditions on the growth and photosynthesis of A. senticosus. Result:The plant height and leaf number were significantly lower than the control group under drought stress conditions，and the leaf area was higher than the control group under drought stress. Net photosynthetic rate，stomata conductance and transpiration rate were not significantly different between the control group and the moderate drought stress group. They were significantly decreased in the severe drought stress group，while the intercellular carbon dioxide concentration increased with the severity of drought stress. With the treatment time，the initial fluorescence was higher in the severe drought stress group than in the control group，and the moderate drought stress group was lower than the control group，the maximum fluorescence was significantly lower in the severe drought stress group than in the control group， potential photochemical efficiency and maximum photochemical efficiency were significantly elevated in the moderate drought stress group. Conclusion:Drought stress can significantly inhibit the growth of A. senticosus. Severe drought conditions can significantly inhibit the photosynthesis of A. senticosus leaves. This effect is related to the regulation of stomatal size，but not related to the activity of photoreaction center.

Chemical constituents of Cassia occidentalis / 中国中药杂志

Compounds(1-6) were isolated and identified from 90% ethanol extract of the stems and leaves of Cassia occidentalis through column chromatography with silica gel, ODS, and Sephadex LH-20. These compounds were identified as 7-hydroxy-5-(3-hydroxy-2-oxopropyl)-2-methyl-4H-chromen-4-one(1), saccharonol A(2), S-6-hydroxymullein(3), 2-methyl-5-acetonyl-7-hydroxy-chromone(4), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(5) and 7,4'-dihydroxyflavone(6) based on their physicochemical and spectroscopic data. Among them, compound 1 was a new compound, and all the compounds were isolated from this plant for the first time. DPPH method was employed to determine the antioxidant activities of these compounds in vitro. Six compounds exhibited weak antioxidant activities.

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via a Network Pharmacology Approach / 中国结合医学杂志

OBJECTIVE@#To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment.@*METHODS@#A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets.@*RESULTS@#Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway.@*CONCLUSIONS@#The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Effect of electroacupuncture at Lower He-Sea points including Yanglingquan (GB 34) on nuclear factor-κB and interleukin-1β in guinea pigs with acute cholecystitis / 针灸推拿医学（英文版）

Objective: To observe the effect of electroacupuncture (EA) at Lower He-Sea points on the expression levels of interleukin-1β (IL-1β) in the serum and gallbladder tissues, and nuclear factor-κB (NF-κB) in gallbladder tissues of the guinea pigs with acute cholecystitis (AC), and to explore whether Yanglingquan (GB 34), the Lower He-Sea point pertaining to Dan Fu (gallbladder), is relatively specific for the Dan Fu (gallbladder) disorders. Methods: Eighty-two healthy guinea pigs were randomly divided into 6 groups according to the random number table method, a blank group, a model group, a Yanglingquan (GB 34) group, a Zusanli (ST 36) group, a Shangjuxu (ST 37) group, and a Xiajuxu (ST 39) group, with 12 guinea pigs in the blank group while 14 in the other groups, respectively, half males and half females in each group. Except for the blank group, guinea pigs in the other groups were injected with E. coli into the gallbladder to establish AC models. Guinea pigs in the blank group were fed routinely without special treatment; those in the model group were daily tied up for 30 min without EA treatment; those in the 4 groups receiving EA treatment were acupunctured at the corresponding Lower He-Sea points after daily binding and stimulated with the SDZ-V EA instrument. After successful modeling and treatment for 5 d, blood was collected from the abdominal aorta of the guinea pigs, and the gallbladder tissues in each group were isolated for hematoxylin-eosin (HE) staining to observe the morphological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-1β level, and immunohistochemistry (IHC) was used to detect the expression levels of NF-κB and IL-1β in gallbladder. Results: On the 3rd day after modeling, the guinea pigs in the five groups with modeling were mentally depressed with decreased appetite, significantly reduced activities, slouch, lassitude, slack and matted fur, and loose stools; two guinea pigs were selected from each group (one male and one female, not included in the final statistics) to isolate the gallbladder after sacrifice; macroscopic observation showed that the gallbladder wall was differently thickened; the bile color was dark green and opaque with particles suspended or accumulated; light microscope observation showed that the submucosal blood vessels of the gallbladder were congested, along with mucosal edema, ulceration, necrosis, shedding, and a large number of inflammatory cells infiltrating in the lamina propria, indicating that the AC model was successfully prepared. Compared with the model group, the gallbladder tissue injuries of the four groups receiving EA treatment were all differently repaired, the serum IL-1β levels were reduced (P<0.01 or P<0.05), and the IL-1β levels in the gallbladder tissues were reduced (P<0.01 or P<0.05). Compared with the model group, the NF-κB expression level in the Yanglingquan (GB 34) group was significantly reduced (P<0.01), but was not statistical different in the Zusanli (ST 36) group, Shangjuxu (ST 37) group and Xiajuxu (ST 39) group (all P>0.05). Compared with the Yanglingquan (GB 34) group, the gallbladder tissues of the Zusanli (ST 36) group, Shangjuxu (ST 37) group and Xiajuxu (ST 39) group were more severely damaged, and the expression levels of serum IL-1β, the NF-κB and IL-1β in the gallbladder tissues were increased (P<0.01 or P<0.05). Intervention effect of Yanglingquan (GB 34) on AC guinea pigs was superior to that of Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). Conclusion: EA at the Lower He-Sea points of the stomach, large intestine, small intestine and gallbladder can produce curative effects on AC guinea pigs and reduced the inflammatory symptoms. Intervention effect of Yanglingquan (GB 34) on AC guinea pigs is superior to that of Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). The mechanism of EA at Yanglingquan (GB 34) in treating AC may be regulating IL-1β and NF-κB to control the inflammatory response and improve the gallbladder tissue damage.