Fully Human Bifunctional Intrabodies Achieve Graded Reduction of Intracellular Tau and Rescue Survival of MAPT Mutation iPSC-derived Neurons.

Tau protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP), spurring development of tau-lowering therapeutic strategies. Here, we report fully human bifunctional anti-tau-PEST intrabodies that bind the mid-domain of tau to block aggregation and degrade tau via the proteasome using the ornithine decarboxylase (ODC) PEST degron. They effectively reduced tau protein in human iPSC-derived cortical neurons in 2D cultures and 3D organoids, including those with the disease-associated tau mutations R5L, N279K, R406W, and V337M. Anti-tau-hPEST intrabodies facilitated efficient ubiquitin-independent proteolysis, in contrast to tau-lowering approaches that rely on the cell's ubiquitination system. Importantly, they counteracted the proteasome impairment observed in V337M patient-derived cortical neurons and significantly improved neuronal survival. By serial mutagenesis, we created variants of the PEST degron that achieved graded levels of tau reduction. Moderate reduction was as effective as high reduction against tau V337M-induced neural cell death.

Assessment of Attractant Combinations for the Management of Red Palm Weevils (Rhynchophorus ferrugineus) in the United Arab Emirates.

This study examined red palm weevil ecology in the United Arab Emirates to develop effective food baits, pheromone, and eco-friendly trapping methods. Three phases of investigation were conducted (from June to December 2023) on date palm farms in Ras Al Khaimah and Abu Dhabi. The first two phases, each 15 days long, were conducted in Ras Al Khaimah, whereas the third phase, 18 days long, was conducted in Abu Dhabi. Chemical attractants, such as existing pheromones and ethyl acetate, a newly synthesized ferruginol pheromone, and food baits, such as original dates, date paste, coconut water, and date palm syrup, were used to attract the weevils. Multi-funnel traps containing various attractant mixes were tested. The main activity of the red palm weevils was observed from 3:00 to 6:00 a.m., with 85.72 ± 3.39% being captured during this period, coinciding with cooler temperatures. When pheromones were added to the food bait, the capture rate increased by 6.95 ± 1.81 times. Combining food bait, ethyl acetate, and pheromones improved the capture rates by 3.14 ± 0.69 times compared to pheromones alone. The newly synthesized pheromone achieved capture rates 2.69 ± 0.07 times higher than those of the commercially available pheromone, confirming its suitability as a red palm weevil attractant.

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy / 中华妇产科杂志

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.@*METHODS@#Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.@*RESULTS@#Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).@*CONCLUSION@#KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma / 中华肿瘤杂志

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

Advances in research on the effects of platelet activation in acute lung injury (Review).

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency or failure caused by various factors inside and outside the lungs. ALI is associated with high morbidity and a poor prognosis in hospitalized patients. The lungs serve as a reservoir for platelet precursor megakaryocytes and are closely associated with platelets. Platelets not only play a central role in hemostasis, coagulation and wound healing, but can also act as inflammatory cells capable of stimulating non-hemostatic immune functions under inflammatory conditions, participating in the progression of various inflammatory diseases, and can result in tissue damage. Therefore, it was speculated that platelets may play an important role in the pathogenesis of ALI. In this review, the latest research progress on secretion of bioactive mediators from platelets, platelet activation-related signaling pathways, and the direct contact reactions between platelets and neutrophils with endothelial cells that result in ALI are described, providing evidence to support the importance of the consideration of platelets in the search for ALI interventional targets.

Experimental study and clinical significance of intravascular angiography in vivo / 中华骨科杂志

Objective:To study the method of intravascular angiography in vivo, analyze the clinical significance, and supply the basis of diagnosis and treatment of related orthopaedic diseases.Methods:The development was realized by improving the developer to increase the local concentration. Based on the study of Lijianmin-Chengkun Complexes and using the theory of magnetic microspheres, Fe 3O 4 magnetic microspheres with amino (negatively charged) shell are used to adsorb the aggregated ionic developer meglumine diatrizoate (positively charged diatrizoate). That is, by improving the method of developer, the magnetic microspheres can carry the developer to make new nanoparticles magnetic imaging composite particles. Under the action of external magnetic field, the magnetic imaging composite particles brought by blood circulation continue to stay and gather in the blood vessels in the magnetic field area, and the developer carried by the magnetic microspheres in the blood vessels in the magnetic field area is concentrated to reach the imaging concentration, so as to realize in vivo intravascular vascular imaging. By adjusting the ratio of the two reagents, the charge can be neutralized and condensed into small groups to improve the development efficiency. Thus, the electron microscope experiment, CT in vivo experiment, rabbit imaging experiment, experimental rabbit tissue picture confirmation, CT in vivo human body (the author is a volunteer) imaging experiment were carried out step by step. Results:Electron microscope experiment: meglumine diatrizoate, scanning electron microscope, the particle diameter is about 20 nm. Scanning electron microscope showed that the diameter of the magnetic microspheres was about 100 nm and the distribution was uniform. After the two reagents are mixed in a certain proportion, the neutralizing charge condenses into small groups, but it still has magnetohydrodynamic properties and strong paramagnetism. In vivo rabbit imaging experiment: the ideal intraosseous vascular imaging of the proximal tibia was captured. The tissue pictures of experimental rabbits confirmed that the distribution of Fe 3O 4 was obviously visible in the blood vessels in the proximal tibia on the side with magnetic field, but not on the side without magnetic field. In vivo human imaging experiment: the ideal intraosseous vascular imaging of the proximal fibula was captured. Conclusion:Through the preparation of new reagent of magnetic imaging composite particles (magnetic microspheres + meglumine diatrizoate), the concentration of in vivo bone developer can be achieved under the action of external magnetic field, and the in vivo external diameter ≥ 0.5mm can be achieved under CT thin-layer scanning.

Ultrasonic differential diagnosis analysis of female urethral diverticulum and vaginal wall cyst / 中华超声影像学杂志

Objective:To explore the clinical and ultrasound image characteristics and differential diagnosis of female urethral diverticulum(UD) and vaginal wall cysts.Methods:A retrospective analysis of the clinical and ultrasound image features of 12 female patients with UD were collected as UD group and 30 patients with vaginal wall cysts confirmed by surgical pathology and clinical follow-up were collected as vaginal wall cysts group in Peking Union Medical College Hospital from January 2017 to May 2021. Ultrasound image characteristics, and the main points of the differential diagnosis of the two were analyzed and summarized.Results:There were no significant differences in the age of the patients and the maximum diameter of the lesions between UD group and vaginal wall cysts group(all P>0.05). Eight cases (66.7%) of female patients with UD had urinary system symptoms, 5 cases (16.7%) of vaginal wall cysts had urinary system symptoms, the difference was statistically significant ( P<0.05); In 10 cases (83.3%) the UD lesions were located in the upper middle and upper pelvic floor, and vaginal wall cyst lesions in 23 cases (76.7%) were located in the lower middle and lower pelvic floor, the difference was statistically significant ( P<0.05). In terms of ultrasound image characteristics, UD lesions were often irregular in shape, surrounding the urethra, with unclear borders, cyst wall thickness >0.1 cm, internal wall not smooth along with calcification, internal visible separation, partly visible to the urethra, and peripheral blood flow signals were abundant. Vaginal wall cysts were mostly round-shaped, not surrounding the urethra, clear borders, thin and smooth walls, less internal partitions, not communication with the urethra, and the peripheral blood flow signals were not abundant. The differences between the two group were statistically significant (all P<0.05). Whether the sound transmission inside the lesion was not statistically significant ( P>0.05). Conclusions:Combined with urinary system symptoms, lesion location, ultrasound characteristics (morphology, whether surrounding the urethra, boundary, cyst wall thickness, inner wall calcification, internal separation, whether it is connected to the urethra, blood flow distribution) can be used to distinguish between UD and vaginal wall cysts, whether the sound transmission inside the lesion cannot be used as the basis for the differential diagnosis of the two.

Pharmacokinetic study of Erlong Zuoci Pill in rats / 中国药科大学学报

@#To establish a quantitative LC-MS/MS method for the simultaneous detection of components of Erlong Zuoci Pill in rat plasma: verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin, and to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill in rats, plasma samples were purified by protein precipitation using methanol as a protein precipitant.Methanol was used as the organic phase and aqueous solution containing 0.1% formic acid was used as the water phase.The quantitative analysis method of verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin was established in negative ion mode, and the validation of bioanalytical method was carried out.Healthy SD rats were selected, and 20 mL/kg (equivalent to the original drug 10 g/kg dose) of Erlong Zuoci Pill extract was administered by intragastric administration.The plasma concentration of the target compounds at different time intervals after administration was determined using the established method, and the pharmacokinetic parameters was calculated by the Phoenix WinNonlin8.3 software using the non-compartmental model.The method validation results showed that verbascoside (r = 0.993 7) and oxypaeoniflorin (r = 0.994 6) had good linear relationship in the concentration range of 0.5-50 ng/mL, echinacoside (r = 0.993 6) and benzoylpaeoniflorin (r = 0.992 6) had good linear relationship in the concentration range of 1-100 ng/mL.The relative standard deviations of the inter- and intra- batch precision of the four compounds were all less than 15%, and the inter- batch and intra- accuracies were between 85% and 115%.Extraction recovery, matrix effect and stability met the relevant requirements.After a single gavage of Erlong Zuoci Pill extract in rats, all the four compounds were rapidly absorbed and eliminated.Oxypaeoniflorin, echinacoside, and benzoylpaeoniflorin showed two peaks in their drug concentration-time curves.Compared with the other three compounds, oxypaeoniflorin has the highest concentration in rat plasma with cmax1 of (24.40 ± 4.78) ng/mL and cmax2 of (22.50 ± 2.70) ng/mL. The results show that the validation results of this method are in line with the guiding principles of biological sample analysis methods, and it can be used to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill extract in rats.

Tirofiban interferes with antibody-mediated transfusion-related acute lung injury by inhibiting platelet-neutrophil binding / 中国输血杂志

【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.

Activation of death receptor 3 signaling pathway prevents antibody-mediated transfusion-related acute lung injury via αDR3 antibody / 中国输血杂志

【Objective】 To explore the efficacy and possible mechanisms of activation of Death receptor 3 (DR3) signaling pathway in the prevention of antibody-mediated transfusion-related acute lung injury (TRALI) via DR3 agonistic (αDR3) antibody. 【Methods】 8-10-week-old male wild-type Balb/c mice (40) were randomly divided into Naïve group, isotype control group, TRALI model group, and intervention group. Mice without any treatment served as Naïve group. Isotype and TRALI model were established by intraperitoneally priming 8-10-week Balb/c mice with LPS 18 h prior to injection of an IgG2a isotype antibody and anti-MHC-Ⅰ antibody via tail vein, respectively. Intervention group: mice were intraperitoneally injected with a single dose of αDR3 antibody (1 mg/kg) on day 1; after 3 days, the mice were challenged with LPS 18 h prior to injection of an anti-MHC-I antibody. The lung tissues and spleens of mice in each group were collected at the mice died or 2 hours after TRALI modeling for the lung injury severity. Spleens were collected to measure the proportion of Treg by flow cytometry. Foxp3, iNOS, and CD206 immunohistochemical staining combining with optical density analysis of lung tissues were used to represent Treg, M1 macrophages and M2 macrophages, respectively. The concentration of IL-6, IL-1β, TNF-α, and IL-10 cytokines in lung tissues was detected via Cytometric Beads Array. 【Results】 Compared with TRALI group, 1) the lung injury of mice were significantly alleviated in intervention group; 2) the proportion of Treg(%) in the spleens (9.295±1.349 vs 2.257±0.610, P<0.05), Foxp3 expression of Treg in the lungs (0.302 6±0.052 6 vs 0.230 2±0.016 3, P<0.05), and the concentration of Treg derived cytokines IL-10 in the lungs (29.52±8.885 vs 8.045±1.911, P<0.05) increased significantly in intervention group; 3) the iNOS expression of M1 macrophages (0.209 6±0.013 9 vs 0.279 6±0.045 2) and the concentration of M1 macrophage derived cytokines IL-6 (23.22±19.35 vs 301.1±157.7), IL-1β (46.76±25.34 vs 307.6±183.8), and TNF-α (45.99±14.16 vs 143.9±44.43) in the lungs was significantly reduced(P<0.05), while CD206 expression of M2 macrophages (0.291 2±0.032 1 vs 0.221 5±0.012 7) and the concentration of M2 macrophage derived IL-10 cytokines (29.52±8.885 vs 8.045±1.911) in the lungs increased significantly in intervention group(P<0.05). 【Conclusion】 Activation of DR3 signaling pathway by αDR3 antibody prevents antibody-mediated TRALI via expanding Treg, which regulates macrophage polarization by IL-10 derived from Treg.

Efficacy analysis of von Willebrand factor in human coagulation factor FⅧ concentrates in China / 中国输血杂志

【Objective】 To obtain the quality information of von Willebrand factor (vWF) in coagulation factor Ⅷ (FⅧ) concentrates in China. 【Methods】 FⅧ concentrates produced by 7 domestic blood product manufactures and 1 foreign manufacture were collected, then FⅧ and vWF contained in FⅧ concentrates were evaluated. 【Results】 The activity loss of vWF was more than 25% in 2 of the 7 domestic FⅧ concentrates. The ratio of vWF activity to FⅧ activity in FⅧ concentrates from different domestic manufactures was significantly different (P<0.05). The ratio in FⅧ concentrates prepared by C, D, F manufacturer was greater than 1, which was similar to that in willate@ approved abroad for the treatment of vWD. The ratio in FⅧ concentrates prepared by E manufacturer was greater than 0.7 and less than 1, and by A, B, G manufacturers was less than 0.5. In addition, the specific activities of FⅧ and vWF were significantly different among different FⅧ concentrates in China (P<0.05), and the specific activities of FⅧ and vWF were much lower than that of willate@. 【Conclusion】 The variation of vWF quality between domestic FⅧ concentrates and willate@ is mainly due to the different in vWF content. After the comprehensive consideration of various indicators, the FⅧ concentrates made by C and D manufacturers may be used in the treatment of vWD.

Potential of modulating fibrinolytic activity in intervention of transfusion-related acute lung injury / 中国输血杂志

Transfusion-related acute lung injury (TRALI), with clinical manifestation, diagnosis and pathological mechanism consistent with acute lung injury(ALI), belongs to a sub-category of ALI. Excessive deposition of fibrin in lung is one of the characteristic of ALI, and reversing fibrin formation is of great significance to intervene ALI. The decrease of fibrinolytic activity is one of the important causes of excessive deposition of fibrin in lung, and also the important pathological feature of TRALI. This article discusses the potential of modulating fibrinolytic activity to intervene TRALI from the perspective of regulating the effectiveness of fibrinolytic activity to intervene ALI.

Research Progress on Anti-atherosclerosis Mechanism of Mongolian Medicine / 中国实验方剂学杂志

Atherosclerosis is one of the most common diseases that threaten human health. How to effectively inhibit atherosclerosis， extend the survival time and improve the quality of life has become one of the most urgent issues to be solved clinically. Mongolian medicine， with a long history of managing human diseases， is an important part in traditional Chinese medicine （TCM） and has distinct ethnic characteristics. It has been gradually formed and developed by absorbing some theories of Tibetan medicine， Indian medicine and relevant knowledge of TCM. Mongolian medicine has many advantages， including but not limited to， low toxicity and diverse structure. However， the action mechanism of Mongolian medicine in preventing and managing atherosclerosis has yet to be fully clarified， which has been a major obstacle for further promotion and application of Mongolian medicine in clinical settings. In this review， the up-to-date research findings on Mongolian medicine were collected， analyzed and summarized， and the anti-atherogenic action mechanism of Mongolian medicine were reviewed from the aspects of anti-inflammatory， lipid-lowering， anti-oxidative stress， vascular endothelial cell protection， and inhibition of vascular smooth muscle cell proliferation and migration.

Ultrasound diagnosis of pelvic lipomatosis and misdiagnosis analysis / 中华超声影像学杂志

Objective:To discuss the value of ultrasound in the diagnosis of pelvic lipomatosis and analyze the causes of misdiagnosis.Methods:A retrospective analysis of 68 cases of pelvic lipomatosis confirmed by operation or imaging in Peking Union Medical College Hospital from January 2000 to December 2018 was made to summarize the characteristics of ultrasonic manifestations.Results:Ultrasonographic findings were as follows: 6 cases (8.8%) had increased fat-like hyperecho in pelvic cavity; 60 cases (88.2%) had abnormal bladder; 42 cases (61.7%) had pyelectasis and 24 cases (35.3%) had ureterectasis. Of the 68 cases, 6 cases (8.8%) were correctly diagnosed; 54 cases (79.4%) were missed; 8 cases (11.8%) were misdiagnosed, including 7 cases (10.3%) of bladder tumor and 1 case (1.5%) of retroperitoneal giant mass.Conclusions:Pelvic lipomatosis has characteristic sonographic features.When urinary tract obstruction and bladder wall thickening are observed, pelvic lipomatosis should be considered. Bladder shape and existence of increasing fat-like hyperecho in the pelvis should be further scanned to reduce the misdiagnosis rate of pelvic lipomatosis.

Black phosphorus loaded with zinc ions for enhanced photothermal therapy of prostate cancer / 药学学报

Prostate cancer is the most common malignant tumor of male reproductive system, which seriously threatens men's health. It has been shown that the existence of zinc ions can inhibit the growth of prostate cancer cells. In addition, photothermal treatment of cancer is attracting more and more attention due to its high accuracy and efficiency. In this study, zinc ions loaded black phosphorus nanosheets (BP-Zn) were prepared, and the photothermal therapy efficiency of the system on human prostate cancer cells (PC-3) was evaluated. The inhibition effect of zinc ions on PC-3 cells was studied. It was demonstrated that the toxicity of zinc ions on PC-3 cells was concentration- and time-dependent. Moreover, it can be seen from in vitro photothermal therapy that the treatment effect of black phosphorus assisted by zinc ions is superior to that of black phosphorus alone. This study further studied the in vivo therapeutic effect of BP-Zn. The results once again confirmed that the combinational photothermal treatment of zinc ions and BP had excellent anti-tumor effect. The animal procedures were approved by the Animal Ethics Committee of Tsinghua Shenzhen International Graduate School.

miR-548c-5p inhibits colorectal cancer cell proliferation by targeting PGK1.

Accumulating studies have implicated that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, the role of miR-548c-5p, a novel identified miRNA in malignancies, in colorectal carcinogenesis remains largely unknown. The present study is aimed to investigate the effect and molecular mechanism of miR-548c-5p in CRC by a sequence of cellular experiments. miR-548c-5p was significantly downregulated, whereas phosphoglycerate kinase 1 (PGK1), a key enzyme for glycolysis, was obviously upregulated in peripheral blood mononuclear cells and cancer tissues from patients with CRC. Besides, miR-548c-5p and PGK1 were negatively associated with each other. The luciferase reporter assay revealed that PGK1 was a targeted gene of miR-548c-5p. Moreover, the proliferation and generation of inflammatory cytokines (TNF-α and IL-6) were significantly inhibited in miR-548c-5p-overexpressed SW480 CRC cells stimulated by lipopolysaccharide (LPS). Accordingly, miR-548c-5p may serve as a cancer suppressor in CRC by targeting PGK1.

Rapid identification of constituents of Urtica hyperborea using UPLC-ESI-Q-TOF-MS/MS method / 中国中药杂志

This paper deals with the application of ultra-performance liquid chromatography tandem quadrupole time of flight mass spectrometry(UPLC-ESI-Q-TOF-MS/MS) method to rapidly determine and analyze the chemical constituents of methanol extract of Urtica hyperborea. We employed UPLC YMC-Triart C18(2. 1 mm×100 mm,1. 9 μm) column to UPLC analysis with acetonitrile-water(containing 0. 4% formic acid) in gradient as mobile phase. The flow rate was 0. 3 m L·min-1 gradient elution and column temperature was 30℃; the injection volume was 4 μL. ESI ion source was used to ensure the data collected in anegative ion mode. The chemical components of U. hyperborea were identified through retention time,exact relative molecular mass,cleavage fragments of MS/MS and reported data.The results indicated that a total of 31 compounds were identified,including 8 flavonoids,14 phenolic compounds,8 phenylpropanoids(4 coumarins and 4 lignans),and 1 steroidal compound,13 of which were confirmed by comparison. The UPLC-ESI-Q-TOF-MS/MS method could rapid identify the chemical components of U. hyperborea. The above compounds were discovered in U. hyperborea for the first time,which could provide theoretical foundation for further research on the basis of the pharmacodynamics of U. hyperborea.

Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS).@*METHODS@#Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing.@*RESULTS@#The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological.@*CONCLUSION@#Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome / 中华医学遗传学杂志

Objective@#To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS).@*Methods@#Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing.@*Results@#The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c. 3779+ 1G>A and c. 5052_c.5053insT, were respectively identified in the 2 patients. Among these, c. 3779+ 1G>A was a previously known pathological mutation, while c. 5052_c.5053insT was unreported previously. Both variants were predicted to be pathological.@*Conclusion@#Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.