Objective To investigate the time-effect relationship of angiogenesis induced by ultrasound.mediated microbubble destruction in the skeletal muscle of rats.Methods Forty-eight healthy SD rats were divided into 4 groups:ultrasound-mediated microbubble destruction group,ultrasound only group,microbubble only group and control group.In ultrasound-mediated mierobubble destruction group, microbubbles were inj ected by vein at a dose of 0.5 ml and the target skeletal muscle was radiated at 2.0W/cm2.In ultrasound only group,the target skeletal muscle was radiated at 2.0 W/cm2.In microbubble only group.microbubbles were injected by vein at a dose of 0.5 ml.The control rats were without ultrasound radiation and microbubbles.On the 3rd,7th,10th,14th,21st and 28th day after the ultrasound radiation,two rats in each group were sacrificed and the target skeletal muscle was harvested for HE staining to observe the microstructure of tissue,immunohistochemistry staining was used to count the microvessel density (MVD),enzyme 1inked inmmunosorbent assay(ELISA)was used to detect the expression of vascular endothelial grouth factor(VEGF).Results Angiogenesis was significant in ultrasound-mediated mierobubhle destruction group,but a little in ultrasound only group.There was not any angiogenesis in either microbubble only group or control group.MVD and VEGF expression of ultrasound-mediated microbubble destruction group arrived at a peak on the 1Oth day as well as on the 14th day of ultrasound group.Conclusions Ultrasound-mediated microbubble destruction can facilliate the endogenous secretion of VEGF quickly and more,and accelerate the angiogenesis in the skeletal muscle.

At present, there is still a lack of comprehensive diagnosis and treatment criteria for pancreatic exocrine insufficiency around the world. Pancreatic surgeons often ignore or misjudge pancreatic exocrine insufficiency secondary to pancreatic cancer, and as a result, pancreatic exocrine insufficiency is not adequately treated, which greatly affects the quality of life of patients with pancreatic cancer. This article summarizes the latest research advances in the pathogenesis, typical symptoms, and diagnostic methods of pancreatic exocrine insufficiency, as well as pancreatic enzyme replacement therapy in different stages of pancreatic cancer. It is pointed out that pancreatic enzyme replacement therapy can significantly improve the quality of life of patients with different stages of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a highly invasive malignant tumor of the digestive system with an extremely poor prognosis. Leukemia inhibitory factor is an important member of the interleukin-6 family and can regulate multiple physiological processes such as cell differentiation, growth, and renewing. This article reviews the mechanism of action of leukemia inhibitory factor in pancreatic ductal adenocarcinoma and the research advances in leukocyte inhibitory factor-targeted therapy based on literature evidence, and the analysis shows that leukemia inhibitory factor plays an important role in the progression, immune escape, and chemotherapy resistance of pancreatic ductal adenocarcinoma and may gradually become a potential biomarker and therapeutic target for pancreatic ductal adenocarcinoma.

ObjectiveTo systematically review the studies about Yiqing Capsules in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat-toxin syndrome and clarify the advantages and therapeutic characteristics of Yiqing capsules， thus providing reference for the decision-making by relevant departments and clues for the clinical and basic research. MethodThe multi-criteria decision analysis （MCDA） model and CSC v2.0 were employed to comprehensively evaluate Yiqing capsules from multiple aspects. ResultThe serious adverse reactions in the spontaneous reporting system （SRS） monitoring data of Yiqing capsules included pruritus， rash， an ddiarrhea， all of which were relieved or cured， without aggravation or interhospital transfer for treatment. Literature data showed that the main clinical adverse reactions were abdominal pain， diarrhea， etc. Both acute toxicity and long-term toxicity tests showed good safety， and thus the safety of Yiqing capsules was rated as grade B. The results of Meta-analysis showed that Yiqing capsules used alone or in combination with other medicines outperformed Niuhuang Jiedu capsules or Western medicine in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat toxin in terms of symptom alleviation， disappearance rate of main symptoms， and recurrence rate of aphtha. Pharmacological and pharmacodynamic studies showed that Yiqing capsules had antimicrobial， antiviral， and anti-inflammatory effects， with the effectiveness rated as grade B. The decision tree model was adopted to analyze the incremental cost-effectiveness ratio. With the threshold of 1 fold per capita GDP and the disappearing rate of pain in gingivitis as the indicator， Yiqing capsules had an economic advantage in the treatment of gingivitis due to heat-toxin compared with Niuhuang Jiedu capsules， and the incremental cost-effectiveness ratio was 0.39 yuan/%， which indicated acceptable cost， with the economy rated as grade B. Yiqing capsules can not only clear heat from Qi aspect but also purge blood fire， serving as the representative prescription of clearing and purging for heat-toxin syndrome. Considering the industrial service system and enterprise innovation， the comprehensive innovation of Yiqing capsules was rated as grade B. Generally， this product does not require personalized treatment plans and features convenient supply， storage， transportation， policy publicity， drug information standards， and easy operation for medical care and patients. The Chinese patent medicine information was complete and in line with national standards， and thus the suitability of Yiqing capsules was rated as grade A. With a low price and good availability and affordability， the accessibility of Yiqing capsules was rated as grade A. The Yiqing capsules prescription， Sanhuang Xiexin decoction， originated from ancient medical books， with rich real-world studies， and thus the traditional Chinese medicine characteristics of Yiqing capsules was rated as grade C. ConclusionThe clinical value of Yiqing capsules was rated as grade B from the "6+1" dimensions， suggesting that it could be conditionally converted into the relevant policy results of basic clinical drug management according to the procedure.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.