BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Left atrial appendage is the most common site of thrombosis in patients with atrial fibrillation.Once the left atrial appendage thrombosis falls off,it will cause serious complications such as stroke and systemic embolism.Diabetes is not only an independent risk factor for atrial fibrillation,but also promotes left atrial appendicular dysfunction and thrombosis in patients with atrial fibrillation.In this article,we reviewed studies on left atrial appendicular function and thrombosis in the setting of diabetes by focusing the underlying mechanisms in order to define reliable evaluation and predictive indicators,as well as effective therapeutic targets.

Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.

Left atrial appendage is the most common site of thrombosis in patients with atrial fibrillation.Once the left atrial appendage thrombosis falls off,it will cause serious complications such as stroke and systemic embolism.Diabetes is not only an independent risk factor for atrial fibrillation,but also promotes left atrial appendicular dysfunction and thrombosis in patients with atrial fibrillation.In this article,we reviewed studies on left atrial appendicular function and thrombosis in the setting of diabetes by focusing the underlying mechanisms in order to define reliable evaluation and predictive indicators,as well as effective therapeutic targets.

Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.

Objective:To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Objective:To investigate the clinical effects of a single lateral-rectus approach (LRA) in the Ti-Robot-assisted treatment of acetabular fractures involving the posterior column.Methods:A retrospective study was conducted to analyze the clinical data of 16 patients with acetabular fracture who had been admitted to Department of Trauma Orthopedics, Taihe Hospital from August 2021 to March 2023. There were 13 males and 3 females with a mean age of 51.5 (35.8, 56.8) years. By the Judet-Letournel classification, there were 4 anterior and posterior semi-transverse fractures, 2 T-shaped fractures, and 10 double-column fractures. The time from injury to operation was 6.0 (5.3, 7.8) d. All their acetabular fractures involving the posterior column were treated by a single LRA with the assistance of a Ti-Robot. Operation time, blood loss, complications, quality of fracture reduction, modified Merle d'Aubigné & Postel scores and acetabular recovery at the last follow-up were recorded.Results:In this cohort, the operation time was (4.1±0.6) h and the blood loss 400 (300, 575) mL. By the Matta evaluation, the fracture reduction was excellent in 10 cases, good in 5 cases, and poor in 1 case. The follow-up time was (11.3±3.9) months. Bone union was achieved in all fractures after 3.0 (2.3, 4.0) months. By the modified Merle d'Aubigné & Postel scores at the last follow-up, 9 cases were excellent, 6 cases were good and 1 case was fair. Injury to the lateral femoral cutaneous nerve occurred in 1 patient, and deep venous thrombosis in 6 patients. Follow-ups revealed no iatrogenic vascular injury, loosening or rupture of internal fixation, or incision infection.Conclusion:A single LRA approach can be used in the minimally invasive treatment assisted by a Ti-Robot for acetabular fractures involving the posterior column, demonstrating advantages of minimal invasion, high reduction quality and good functional recovery of the hip joint.

Objective:To analyze the clinicopathological characteristics, treatment responses and kidney outcomes of patients with atypical membranous nephropathy (MN), and to provide information for the clinical practice.Methods:The clinical data of patients with atypical MN and synchronous primary MN who were diagnosed, treated and followed up in Peking University First Hospital from January 2008 to June 2020 were retrospectively collected and analyzed. Clinicopathological features, treatment responses and kidney prognosis were compared between the two groups. The expression of phospholipase A2 receptor (PLA2R) in kidney tissues was detected by immunofluorescence. Serum anti-PLA2R antibody was detected by enzyme-linked immunosorbent assay. Clinicopathological indexes were compared between PLA2R-related MN group and non-PLA2R-related MN group. Kaplan-Meier (Log-rank test) survival curve and multivariate Cox regression analysis methods were used to analyze the influencing factors of kidney prognosis in patients with atypical MN. The primary endpoint of renal adverse outcome was renal insufficiency, defined as end-stage renal disease or estimated glomerular filtration rate (eGFR) decline>30% baseline and<60 ml·min -1·(1.73 m 2) -1. Results:A total of 65 atypical MN patients were enrolled in this study. Compared with primary MN ( n=324), patients with atypical MN had younger age ( Z=-4.229, P<0.001), higher proportion of hematuria ( χ2=5.555, P=0.018), higher level of urinary protein ( Z=2.228, P=0.026) and lower level of eGFR ( t=-5.108, P<0.001); the proportion of IgG4 deposition in kidneys was lower ( χ2=8.081, P=0.004), and the proportions of IgA ( χ2=16.969, P<0.001) and IgM ( χ2=9.281, P=0.002) deposition were higher. There was no significant difference on gender, serum albumin, positive proportion of anti-PLA2R antibody, anti-PLA2R antibody level and kidney C3/C1q deposition between the two groups (all P>0.05). The proportions of atypical MN patients receiving renin-angiotensin aldosterone system inhibitors (49.3% vs 57.1%), calcineurin inhibitors (27.7% vs 19.1%) and cyclophosphamide (21.5% vs 23.8%) were comparable to those of primary MN patients (all P>0.05). The rates of clinical remission (80.0% vs 77.2%), partial remission (44.6% vs 44.1%), complete remission (35.4% vs 33.1%), spontaneous remission (36.9% vs 42.6%), response to cyclophosphamide (85.7% vs 81.8%), response to calcineurin inhibitor (88.9% vs 79.0%), and relapse (30.8% vs 26.8%) in atypical MN patients were comparable to those in primary MN patients (all P>0.05). During the follow-up 30.0(21.5, 61.5) months, 15 atypical MN patients (23.1%) had eGFR reduction>30%, among whom 7 patients (10.8%) had eGFR reduction>50% and 3 patients (4.6%) had end-stage kidney disease. There was no significant difference on poor kidney prognosis between the two groups (all P>0.05). Kaplan-Meier survival curve showed that patients with age>39 years old ( χ2=10.092, P=0.001), eGFR≤100 ml·min -1·(1.73 m 2) -1( χ2=5.491, P=0.019), tubular interstitial lesion ( χ2=6.999, P=0.008) and no nephropathy remission ( χ2=22.952, P<0.001) had earlier poor renal prognosis. Multivariate Cox regression analysis showed that no nephropathy remission ( HR=12.604, 95% CI 2.691-59.037, P=0.001) was an independent influencing factor for poor renal prognosis in atypical MN patients. Conclusion:No significant difference is found between atypical MN and primary MN on treatment responses and kidney prognosis, which implies that clinical practice of atypical MN can be performed by referring to the guidelines and experience of primary MN.

Adult ; Cyclosporine ; Glomerulosclerosis, Focal Segmental/drug therapy* ; Humans ; Leflunomide/therapeutic use* ; Nephrosis, Lipoid/drug therapy* ; Nephrotic Syndrome ; Steroids

Objective:To explore the risk factors for atrial fibrillation(AF)in elderly Chinese patients with severe valvular heart disease(VHD).Methods:This was a cross-sectional study and consecutively enrolled 978 elderly patients with severe VHD diagnosed in 18 Class A tertiary hospitals across the country from September 2021 to March 2022, including 322(32.9%)patients with concurrent AF.Clinical and echocardiographic data were collected to analyze the risk factors for AF.Results:Among VHD patients, compared with the non-AF group, the AF group was older, had a higher female ratio, higher diastolic blood pressure, higher proportions with cerebrovascular disease and chronic kidney disease, lower serum low density lipoprotein cholesterol and higher serum creatinine, amino-terminal A-type natriuretion peptide and glycosylated hemoglobin.As for echocardiographic parameters, the left atrial diameter was larger, the left ventricular end-diastolic diameter, interventricular septum thickness, and left ventricular posterior wall thickness were smaller in the AF group than in the non-AF group.All of the differences were statistically significant(all P<0.05). The results of multivariate Logistic regression analysis showed that the left atrial anteroposterior diameter increased( OR=1.166, P<0.01), the left ventricular end-diastolic diameter decreased( OR=0.929, P<0.01), and advanced age( OR=1.051, P<0.05)was an independent risk factor for elderly VHD patients with concurrent AF. Conclusions:In elderly patients with severe VHD, advanced age, an increased left atrial anteroposterior diameter, and a decreased left ventricular end-diastolic diameter were independently associated with AF.Therefore, evaluation of cardiac structure and regular follow-up should be performed in elderly patients with severe VHD for early intervention to reduce the incidence of AF.