In recent years， mesenchymal stem cells （MSC） have been widely explored in the treatment of liver diseases due to their characteristics of multipotential differentiation and immunomodulatory capabilities. Current evidence has shown that MSC therapy can improve liver function， alleviate fibrosis， and promote hepatocyte regeneration in end-stage liver diseases such as liver cirrhosis and liver failure. However， safety concerns have emerged with the increasing clinical use of MSC. This article systematically reviews the acute adverse reactions and long-term safety of MSC-based therapies for liver diseases. It is shown that MSC therapy has a good overall safety profile， with common acute adverse reactions of fever， rash， and mild allergy， most of which are self-limiting or can be alleviated by symptomatic treatment. No clear evidence of tumorigenesis has been reported in long-term follow-up， but some studies have suggested a potential association between MSC and the development of hepatocellular carcinoma. In addition， the risks of embolism， immune rejection， and infection susceptibility should be monitored continuously. Overall， MSC therapy shows good prospects in short-term efficacy and safety in the treatment of liver diseases， but clinical studies with a large sample size and a long follow-up period are needed to further validate its long-term safety and efficacy.

To summarize the clinical characteristics, antibody spectrum and neuroelectrophysiological features of autoimmune nodopathy(AN), and to explore the phenotypic differences among different antibody-positive subgroups.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Objective:To evaluate the clinical features and risk factors of anastomotic leakage (AL) in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (nCRT) followed by laparoscopic radical resection and proctocol ostomy.Method:Clinicla data of LARC patients receiving neoadjuvant chemoradiotherapy followed by laparoscopic radical resection and proctocol ostomy admitted to Peking Union Medical College Hospital between Jan 2019 and Oct 2023 was enrolled. According to the occurrence of AL, patients were divided into AL group and non-AL group.Results:After propersity matching score(PSM), there were 40 patients (33.4%) and 80 patients (66.6%) in the AL and non-AL group, respectively. The first-onset symptoms of AL were abnormal character and color of the drainage (23 cases, 57.5%) and fever (14 cases, 35.0%). About 82.5% of the AL were graded as B,and all 36 patients (90.0%) were managed consveratively by fully drainage anti-infection therapy. Logistic regression analysis indicated that tumor circumferential range more than 1/2 cycle ( OR=5.95, 95% CI:2.12-1.67, P=0.004), male ( OR=4.28, 95% CI:1.22-15.00, P=0.023) and high-ligation of Inferior mesenteric artery ( OR=8.08, 95% CI:1.86-37.78, P=0.006) were independent risk factors of AL. Conclusions:In this series, grade-B AL ranks the top of the incidence, and all were cured by conservative therapy. Special attention should be paid to those patients with the characteristics of male, tumor circumferential range more than 1/2 cycle, and high-ligation of inferior mesenteric artery.

Objective:To detect the association of tumor circumferential involvement range (CIR) with neoadjuvant chemoradiotherapy (NCRT) efficacy and long-term survival outcomes in locally advanced rectal cancer (LARC) patients.Methods:Clinical data of 451 patients admitted to our hospital from January, 2018 to January, 2022 were retrospectively collected. According to the CIRs as determined by rectal magnetic resonance imaging, patients were divided into the High group (≥2/3 cycle, 270 patients) and the Low group (＜2/3 cycle, 181 patients). The primary outcome was three-year disease-free survival. The baseline characteristics, pathological features, and survival outcomes were compared.Results:Compared to patients in the Low group, patients in the High group exhibited significantly larger tumor vertical diameters [(4.7±1.7) vs. (3.6±1.4)cm, P＜0.001], higher rates of mrT4 stage (37.8% vs. 13.2%, P＜0.001), and higher rates of positive mesorectal fascia (54.1% vs. 29.8%, P＜0.001) and extramural vascular invasion (55.6% vs. 38.1%, P＜0.001). Patients in the High group were mainly pT3-4 stages (46.7% vs. 30.9%, P=0.002), with significantly lower rates of pathological complete response (22.2% vs. 33.1%, P=0.010) , poorer tumor regression grades (48.9% vs. 60.8%, P=0.013), and higher rates of positive peripheral nerve invasion (11.5% vs. 5.5%, P=0.031), as compared to patients in the Low group. The median follow-up time was 40 months. About 11 (2.4%) and 48 patients (10.6%) experienced tumor local recurrence and distant metastasis, respectively. The recurrence rates were 2.2% and 2.6%, and the distant metastasis rates were 7.7% and 12.6%, respectively, in the Low group and the High group, with no statistical significance ( P=0.957, P=0.096). The three-year disease-free survival in the High group was significantly lower than that in the Low group (84.4% vs. 92.4%, P=0.014). Conclusions:The CIR is closely related to tumor burden, which can judge tumor response to NCRT, and is negatively related to survival prognosis. For patients who have more than a 2/3 cycle of CIR, intensified or consolidated treatments may be required to improve survival outcomes.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Aim To investigate the role of RNF8 in the proliferation,invasion and migration of hepatocellular carcinoma and in the promotion of epithelial-mesenchy-mal transition(EMT);to clarify the regulatory mecha-nism of RNF8 on hepatocellular carcinoma cells.Methods Immunohistochemistry was used to detect the expression of RNF8 and RhoA in human hepatocel-lular carcinoma tissues and adjacent tissues;Western blot and RT-PCR were used to detect the expression levels of RNF8 and RhoA in human normal hepatocytes and hepatocellular carcinoma cells.RNF8 was overex-pressed in HepG2 cells,and siRNA interference was used to downregulate the expression of RNF8.The cell experimental groups were as follows:control group(Control,normal HepG2 cells),RNF8 overexpression group,RNF8 low expression group(siRNA RNF8),RNF8 overexpression+Rhosin(20 μmol·L-1,RhoA blocker)group.The cell proliferation ability was detected by CCK-8 method;the cell migration ability was detected by scratch test;the cell invasion ability was detected by Transwell test;finally,the expression levels of RNF8,RhoA,PCNA,CyclinD1,N-cadherin,vimentin,Slug,and E-cadherin proteins and mRNA were detected by Western blot and RT-PCR.Results The expression of RNF8 and RhoA in liver cancer tissues and liver cancer cells significantly increased;after RNF8 knockdown,the proliferation,migration,in-vasion and EMT of liver cancer cells were significantly inhibited,while overexpression of RNF8 significantly increased the proliferation,migration,invasion ability of liver cancer cells and promoted EMT.RhoA showed a positive correlation with knockdown and overexpression of RNF8.When RNF8 was overexpressed and RhoA blocker was given at the same time,the phenomenon of overexpression of RNF8 increasing the proliferation,mi-gration,invasion ability and promoting EMT of liver cancer cells was significantly reversed.Conclusions RNF8 can promote the proliferation,migration,invasion and EMT of liver cancer cells,and at the same time promote the expression of RhoA.RNF8 promotes the progression of hepatocellular carcinoma by regulating RhoA to promote EMT.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To analyze the types and characteristics of post-operative complications in colorectal cancer patients aged over 85 years undergoing laparoscopic surgery, and to summarize peri-operative management strategies.Methods:This was an observational study. Inclusion criteria: pathologically confirmed adenocarcinoma; tumor located in ileocecum, ascending colon, transverse colon, descending colon, sigmoid colon, or rectum; undergoing laparoscopic radical resection for colorectal cancer; complete clinical data. Exclusion criteria included distant metastasis, synchronous resection of multiple primary cancers, simultaneous liver metastasis surgery, and follow-up duration <1 month. A retrospective analysis was conducted on 191 patients of colorectal cancer patients aged over 85 years who underwent laparoscopic radical surgery in the General Surgery Department at Peking Union Medical College Hospital from January 2019 to January 2024. Among 191 patients, 107 patients (56.0%) had colon cancer and 84 (44.0%) rectal cancer. All patients received "home-based prehabilitation" and post-operative "enhanced recovery after surgery" protocols. Patient characteristics, peri-operative complication types, treatments, and outcomes were analyzed.Results:Post-operative complications occurred in 97 patients (50.8%), including 53 colon cancer patients (54.6%) and 44 rectal cancer patients (45.4%). Comorbidities existed in 88 patients (90.7%), with 93 patients (95.9%) classified as ASA II-III pre-operatively and 86 (88.7%) having nutritional risks. Surgical procedures included Dixon procedure (38 patients, 39.2%), right hemicolectomy (33 patients, 34.0%), sigmoidectomy (10 patients, 10.3%), and 17 patients (17.5%) received prophylactic stomas. Complication types comprised non-anastomotic infections (38 patients, 19.9%), intestinal flora disorder (26 patients, 13.6%), anastomotic/wound/stoma-related complications (16 patients, 8.4%), thrombotic/hemorrhagic events (6 patients, 3.1%), and others (11 patients, 5.8%). By Clavien-Dindo classification: Grade I (12 patients, 6.3%), Grade II (69 patients, 36.1%), Grade III (12 patients, 6.3%), and Grade IV (4 patients, 2.1%). Except for 5 patients (2.6%) requiring unplanned re-operation, all complications resolved with conservative treatment. The median duration of post-operative hospitalization was 9.5 days (7–13).Conclusion:Non-anastomotic infections and intestinal flora disorder constitute predominant complications after laparoscopic surgery in colorectal cancer patients aged over 85 years, mostly manageable with conservative treatment. Strengthened peri-operative management incorporating pre-operative prehabilitation and post-operative enhanced recovery after surgery protocols is crucial for patients aged over 85 years.