Tendon-bone healing is a complex biological process. Multiple signaling pathways are involved in tendon-bone healing， including transforming growth factor-β signaling pathway， bone morphogenetic protein signaling pathway， Wnt signaling pathway， fibroblast growth factor signaling pathway and nuclear transcription factor-κB signaling pathway. This paper summarizes the research status of traditional Chinese medicine regulating related signaling pathways to promote tendon-bone healing. It is found that a variety of traditional Chinese medicine monomers or herbal extracts （such as baicalein， icariin， total flavonoids of Drynaria fortunei， parthenolide， total saponins of Panax notoginseng， etc.） and traditional Chinese medicine compounds （such as Taohong siwu decoction， Liuwei dihuang pill， Xujin jiegu liquid， etc.） can promote bone formation， anti-inflammatory， anti-oxidation， by regulating the above signaling pathways， thereby effectively promoting tendon-bone healing.

Interleukin-1 receptor-related kinase (IRAK4) is a widely expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 plays a pivotal role as a key kinase within the downstream signaling pathway cascades of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs). The signaling pathways orchestrated by IRAK4 are integral to inflammatory responses, and its overexpression is implicated in the pathogenesis of inflammatory diseases, autoimmune disorders, and cancer. Consequently, targeting IRAK4-mediated signaling pathways has emerged as a promising therapeutic strategy. Small molecule inhibitors and degraders designed to modulate IRAK4 have shown efficacy in mitigating related diseases. In this paper, we will provide a detailed description of the structure and function of IRAK4, the role of IRAK4 in related diseases, as well as the currently reported small molecule inhibitors and degraders of IRAK4. It is expected to provide new directions for enriching the clinical treatment of inflammation and related diseases.

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6C^hi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF⁺CD4⁺ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39⁺CD73⁺ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A_2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Objective: By investigating the genotype and evolutionary variation of hantavirus (HV) in Tiantai county, a national surveillance site for hemorrhagic fever with renal syndrome (HFRS) was set in Zhejiang province, from 2011 to 2018, to reveal the molecular epidemiological characteristics of hantavirus (HV) in Tiantai. Methods: Total RNA was extracted from ultrasound treated HV antigen- positive rat lung samples in Tiantai from 2011 to 2018. After cDNA was prepared, nested PCR was used to amplify partial sequence of M fragments by using specific primers of HV. The sequences of HV in Tiantai from 2011 to 2018 were compared with other known HV sequences in order to identify the genotype and analyze the evolution and variation of the virus. Results: In 67 HV antigen-positive lung specimens, 31 were positive in nested PCR amplification with type-specific primers, including 30 Hantaan virus (HTNV) positive samples, 1 Seoul virus (SEOV) positive sample, and all the 31 samples were from Apodemus agrarius. The phylogenetic tree based on partial M segment was divided into monophyletic group, 30 strains were distributed in HTNV group and 1 was in SEOV group. The HTNV strain Tiantai T2018-130 was independently in one branch, sharing 84.8%-87.9% homology with other strains both at home and abroad, including 29 strains in HTNV group in Tiantai. The other 29 HTNV strains in Tiantai showed closer relationship. The SEOV strain T2016-31 from Apodemus agrarius showed closer relationship with previous strains of SEOV, Tiantai ZT71, ZT10 and Z37 strains of Wenzhou, Zhejiang province. Conclusions HTNV, the main genotype of HV in Tiantai of Zhejiang province, showed obvious geographic clustering, but the strain T2018-130 was distinct from the others in Tiantai. Meanwhile, by sequence analysis, we confirmed that The SEOV strain T2016-31 existed in in Apodemus agrarius, indicating there was a phenomenon of "spillover" between virus and host in SEOV evolution.

Objective: To investigate the imaging characteristics and the cause for the misdiagnosis and mistreatment of epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) in order to improve the accuracy of preoperative diagnosis. Methods: The clinical and imaging data of 8 patients with ECIPAS confirmed by pathology in Zhejiang Provincial People′s Hospital between June 2008 and February 2018 were collected. The reason for doctor visit included CA19-9 elevation (n=1) and pancreatic occupying mass (n=9) during physical examination and no obvious symptoms were reported. CT and MRI imaging features, diagnosis and treatment were analyzed. Results: The lesions in 8 cases of ECIPAS were all located in the tail of the pancreas and were cystic and solid. The lesions in 3 cases were mainly cystic and the cystic wall was linear, whose CT density, MRI signal and enhancement pattern cannot be compared with those of the spleen. Solid components can be seen in 5 cases, and the CT density or MR signal of the solid part was similar to that of the spleen. After enhancement, the solid part at the artery stage was uniformly enhanced and the enhancement degree was higher than that of the pancreas. Similar to the spleen, it was uniformly enhanced at the portal vein stage and the enhancement degree of the spleen was consistent. All 8 patients were diagnosed with pancreatic neoplastic lesions before surgery, and 1 patient had pancreatic fistula and peripancreatic necrosis after surgery. Postoperative pathology confirmed the diagnosis of ECIPAS. Conclusions Improving the radiologists and clinicians′ cognition of the imaging manifestations of ECIPAS can improve the accuracy of preoperative diagnosis and avoid unnecessary surgery due to misdiagnosis.

Cerebral artery embolism is a rare but serious complication of facial plastic surgery. This paper reports a case of severe total cerebral arterial fat embolism caused by facial autologous fat injection. The patient past away after 40 hours of treatment. The cause of this total cerebral artery embolism patient was analyzed by tracing relevant medical history and cephalic CTA examination. By studying this case, we hope to reduce the occurrence of similar situations in the future.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
Abdomen ; surgery ; China ; Drainage ; methods ; Evidence-Based Medicine ; Humans ; Practice Guidelines as Topic ; Societies, Medical ; organization & administration ; Surgical Wound Infection ; prevention & control ; Traumatology ; organization & administration ; Vacuum

Eight new C-diterpenoid alkaloid arabinosides, named aconicarmichosides E-L (-), were isolated from an aqueous extract of the lateral roots of (Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds -, together with the previously reported four neoline 14--arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg (i.p.), as compared with the black control, compounds , , and - exhibited analgesic effects with >65.6% inhibitions against acetic acid-induced writhing of mice. Structure-activity relationship was also discussed.

Chronic inflammatory response often involves in the progression of disease in all organ system.While inflammation has been a highlight topic of study in many decades for patho-genesis or identifying drug targets to disease-associated inflam-mation.In this paper,the main fundamental research areas of projects funded by NSFC on inflammation during 2010 ~2015 are reviewed.The features and research types of projects are an-alyzed.