The bone morphogenetic protein(BMP),as a member of the transforming growth factor beta(TGF-?) family,plays a pivotal role in the formation,induction,maintenance and repair of the bone.The expression level of BMPs has a direct influence on the differentiation of mesenchymal osteoprogenitors and the regulation of osteoblastic features.Among BMPs,BMP-2 is the most widely studied and has the strongest activity in inducing bone formation.This article reviews the current advances in researches on BMP-2 for bone repair.

Objective:To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the maturation and differentiation of dendritic cells (DCs) and the mechanism involved in the regulation of inflammation in patients with severe acute pancreatitis (SAP).Methods:The full-term fetal umbilical cords(about 4-5 cm) were collected from Zhengzhou Central Hospital Affiliated to Zhengzhou University after cesarean section. hUC-MSCs were isolated and cultured in primary culture. Flow cytometry was used for phenotype identification, adipogenic and osteogenic staining. 20 ml peripheral blood samples from 5 SAP patients were collected, and monocytes were isolated using lymphocyte separation solution and then induced by adding granulocyte macrophage colony-stimulating factor (GM-CSF), IL-4 and tumor necrosis factor (TNF)-α and cultured as DCs. According to different culture methods, DCs were divided into DCs group, hUC-MSCs+ DCs group and hUC-MSCs+ DCs+ NS398 group (NS398 was a specific inhibitor of COX-2, a downstream regulatory gene of NF-κB). The phenotype of DCs was detected by flow cytometry, and the levels of IL-1β, IL-lα, IL-2, IL-6 and IL-10 in the supernatant of cell culture for 24 hours were determined. The expression of toll like receptor (TLR)-4, IKKα and NF-κB-p65 were detected by Western blot.Results:The hUC-MSCs were successfully cultured, and their surface markers CD 90, CD 105 and CD 73 were positively expressed, and they could differentiate into adipocytes and bone cells. With the prolongation of culture time, DCs differentiated from immature to mature cells. Compared with the DCs group, the proportion of regulatory DCs (regDCs) was increased in the hUC-MSCs+ DCs group, and the marker CD 11b was significantly up regulated [(14.26±1.25)% vs (4. 87±0.58)%], CD 1a and CD 11c were significantly down regulated [(2.81±0.34)% vs (13.62±1.52)%, (3.88±0.5)% vs (11. 8±1.22)%]. All the difference were statistically significant ( P<0.05). The expression of IL-1β, INF-γ and IL-6 in culture supernatant were down regulated, but the difference was not statistically significant; The pro-inflammatory factor IL-1α was significantly decreased [(14.91±2.58)ng/L vs (30.19±7.75)ng/L], and the anti-inflammatory factor IL-10 was significantly increased [ (17.03±4.69)ng/L vs (1.83±0.14)ng/L]. The expression levels of NF-κB-p65 and TLR4 were significantly down regulated (0.74±0.02 vs 0.97±0.01, 0.89±0.01 vs 1.72±0.01), and the expression of IKKα protein was significantly up regulated (1.12±0.01 vs 0.21±0.01) in hUC-MSCs-DCs group. All the differences were statistically significant (all P value<0.05). Compared with DCs group and hUC-MSCs+ DCs group, the expression levels of NF-κB-p65 and TLR4 were significantly down regulated (0.34±0.01 vs 0.97±0.01, 0.74±0.02 and 0.14±0.01 vs 1.72±0.01, 0.89±0.01), while the expression of IKKα protein was significantly up regulated (1.68±0.01 vs 0.21±0.01, 1.12±0.01) in hUC-MSCs+ DCS+ NS398 group. All the differences were statistically significant (all P value<0.05). Conclusions:In SAP patients, hUC-MSCs can inhibit the maturation and differentiation of DCs, and induce CD 11bhigh CD 1alow CD 11clowrregDCs to participate in immune regulation, which may play an anti-inflammatory role by inhibiting the inflammatory cascade through TLR4/IKKα/NF-κB/COX-2 pathway.

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′s exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.