Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered—namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants’ onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.

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.

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.

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.

Objective To compare the clinical outcomes of mini-invasive plate osteosynthesis ( MIPO ) and conventional open plating for complex fractures of midshaft clavicle. Methods The authors retrospec-tively reviewed the data of complex fractures of midshaft clavicle ( AO/OTA types 15-B2 and 15-B3 ) which had been treated with MIPO or conventional open plating between January 2010 to February 2016. Forty-one patients were treated with MIPO and 43 with conventional open plating. The 2 groups were compared in terms of incision length, hospital stay, bone union time, postoperative Constant score and Disabilities of the Arm, Shoulder and Hand ( DASH ) score, patients'satisfaction and complications. Results The average follow-up was 21. 2 ± 9. 2 months for MIPO group and 23. 1 ± 11. 8 months for conventional open plating group. The incision length ( 4. 3 ± 0. 5 cm ) , hospital stay ( 7. 7 ± 1. 9 d ) and union time ( 10. 6 ± 3. 2 w ) in the MIPO group were signifi-cantly shorter than those in the conventional open plating group ( 8. 4 ± 1. 3 cm, 9. 6 ± 3. 1 d and 12. 3 ± 3. 9 w, respectively ) ( P <0. 05 ) . The MIPO group had significantly lower incidences of hypertrophic scarring and dysesthesia in the area of incision but significantly higher patients'satisfaction than the conventional open plating group ( P <0. 05 ) . There were no significant differences in the Constant score or DASH score at 3 months, 6 months and the final follow-up ( P > 0. 05 ) . Conclusion In the treatment of complex fractures of midshaft clavicle, although both MIPO and conventional open plating can lead to similar functional outcomes, MIPO may be advantageous over conventional open plating in smaller surgical incision, more rapid fracture union, shorter hospital stay and higher patients'satisfaction.

Objective To evaluate the clinical outcomes of split fractures of humeral greater tuberosity treated by our self-designed new type of anatomical locking plate.Methods From September 2012 to February 2017,23 patients were treated for acute split fracture of the humeral greater tuberosity using our self-designed new type of anatomical locking plate.They were 13 males and 10 females with a mean age of 52.8 years (range,from 25 to 81 years).Of them,6 were beyond 60 years old, 12 had comminuted fracture,10 were complicated with glenohumeral dislocation,and 12 with rotator cuff tear.The patients were evaluated clinically with Constant-Murley score,visual analog scale (VAS),range of motion and complications at the last follow-ups.Results This series were followed up for 12 to 30 months (mean,23.2 months).All the fractures healed after an average time of 10.6 weeks (range,from 8 to 12 weeks).Their mean Constant-Murley Score was 92.1 points (range,from 70 to 100 points),giving an excellent and good rate of 95.7％ (22/23);their VAS scores averaged 0.8 points (range,from 0 to 4 points).Their forward flexion averaged 160.6°,abduction 157.8°,external rotation 46.4°,and internal rotation up to the T11 level,respectively.Their complications rate was 17.4％ (4/23).One case of axillary nerve injury,one case of relapse of glenohumeral dislocation at sports,and 2 cases of stiff shoulder were observed.Conclusion Split fractures of the humeral greater tuberosity can be successfully treated with our new type of anatomical locking plate which serves as a new alternative treatment.

OBJECTIVE: To investigate the long-term outcome of organ preservation with local excision or "watch and wait" strategy for mid-low rectal cancer patients evaluated as clinical complete remission (cCR) or near-cCR following neoadjuvant chemoradiotherapy (NCRT). METHODS: Clinical data of 62 mid-low rectal cancer patients evaluated as cCR/near-cCR after NCRT undergoing organ preservation surgery with local excision or receiving "watch and wait" strategy at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from March 2011 to August 2017 were retrospectively analyzed. According to the approximate 1:2 pairing, 123 patients who underwent radical resection with complete pathological remission(ypCR) after neoadjuvant chemotherapy during the same period were selected for prognosis comparison. The primary endpoint of the study was 3-year non-regrowth disease-free survival (NR-DFS) and tumor specific survival (CSS). Survival analysis was performed using the Kaplan-Meier curve (Log-rank method). The secondary endpoint of the study was 3-year organ preservation and sphincter preservation. RESULTS: The retrospective study included 38 male and 24 female patients. The median age was 60 (31-79) years and the median distance from tumor to anal verge was 4(1-8) cm. The ratio of cCR and near-cCR was 79.0%(49/62) and 21.0%(13/62) respectively. Local regrowth rate was 24.2%(15/62). Of 15 with tumor regrowth, 9 patients received salvage radical rectal resection and no local recurrence was found during follow-up; 4 patients received salvage local excision among whom one patient had a local recurrence occurred patient; 2 patients refused further surgery. The overall metastasis rate was 8.1%(5/62), including resectable metastasis(4.8%,3/62) and unresectable metastasis (3.2%,2/62). The valid 3-year organ preservation rate and sphincter preservation rate were 85.5%(53/62) and 95.2%(59/62) respectively. The median follow-up was 36.2(8.6-89.0) months. The 3-year NR-DFS of patients with cCR and near-cCR was 88.6% and 83.1% respectively, which was not significantly different to that of patients with ypCR (94.7%, P=0.217). The 3-year CSS of patients with cCR and near-cCR was both 100%, which was not significantly different to that of patients with ypCR(93.4%, P=0.186). CONCLUSIONS Mid-low rectal cancer patients with cCR or near-cCR after NCRT undergoing organ preservation with local excision or receiving "watch and wait" strategy have good long-term prognosis with low rates of local tumor regrowth and distant metastasis, which is similar to those with ypCR after radical surgery. This treatment mode may be used as an option for organ preservation in mid-low rectal cancer patients with good tumor remission after NCRT.
Adult ; Aged ; Chemoradiotherapy ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; diagnosis ; therapy ; Retrospective Studies ; Treatment Outcome ; Watchful Waiting

OBJECTIVETo investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT).

METHODFrom March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years.

RESULTSA total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%.

CONCLUSIONSOrgan preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.

Adult ; Aged ; Anal Canal ; surgery ; Biopsy ; Chemoradiotherapy ; Digestive System Surgical Procedures ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; secondary ; surgery ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; prevention & control ; Organ Preservation ; Quality of Life ; Rectal Neoplasms ; mortality ; surgery ; therapy ; Reoperation ; Salvage Therapy ; Survival Rate ; Treatment Outcome ; Watchful Waiting ; methods

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on autophagy and the secretion of chemokine receptor CXCR4 induced by low-dose immunosuppressive durgs.Methods Flow cytometry was used to detect the changes of hUC-MSCs surface markers after treatment with low-dose tacrolimus and rapamycin.The effect of treatment with tacrolimus and rapamycin on proliferation of hUC-MSCs was analyzed with WST-1 assay.Regular RT-PCR was applied to analyze the mRNAs expression of ligands such as LC3B,Atg5 and Beclin1 in hUC-MSCs.Western blotting was carried out to detect the expression of LC3B,Atg5,Beclin1 and p-ULK1 in hUC-MSCs after treatment with tacrolimus and rapamycin.The secretion of chemokine receptor CXCR4 in hUC-MSCs was analyzed under the state of autophay by flow cytometry.Results Flow cytometry analysis confirmed low-dose immunosuppressive drugs tacrolimus and rapamycin did not cause changes in hUC-MSCs phenotypes significantly.Low-dose tacrolimus had no cytotoxic effect on hUC-MSCs,while,rapamycin could inhibit the proliferation of hUC-MSCs after 24 h or 48 h,with survival rate being 73.66％ and 68.81％ (P＜0.05) of controls,respectively.Moreover,both tacrolimus and rapamycin could inhibit PI3K/AKt/mTOR signaling pathway to activate hUC-MSCs autophagy,and the related proteins of LC3B,Atg5 and Beclin1 increased significantly and induced the up-regulation of CXCR4 secretion.Conclusion Our results here demonstrated that low-dose tacrolimus and rapamycin induce autophagy in hUC-MSCs and promote the secretion of CXCR4.