Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

The morbidity and mortality rate of cardiogenic stroke caused by atrial fibrillation is high,and anticoagulant therapy is the first therapeutic choice in the management of atrial fibrillation.International normalized ratio of warfarin should be strictly controlled at 2.0-3.0.The efficacy of direct oral anticoagulants for preventing embolism events is non-inferior to warfarin,but the risk of bleeding is significantly lower.Severe renal function decline has a great impact on the efficacy and safety of oral anticoagulants.The use of oral anticoagulants in patients with end-stage renal disease is now still controversial.This article reviews the research progress of oral anticoagulant therapy in patients with non-valvular atrial fibrillation complicated with end-stage renal disease.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

The morbidity and mortality rate of cardiogenic stroke caused by atrial fibrillation is high,and anticoagulant therapy is the first therapeutic choice in the management of atrial fibrillation.International normalized ratio of warfarin should be strictly controlled at 2.0-3.0.The efficacy of direct oral anticoagulants for preventing embolism events is non-inferior to warfarin,but the risk of bleeding is significantly lower.Severe renal function decline has a great impact on the efficacy and safety of oral anticoagulants.The use of oral anticoagulants in patients with end-stage renal disease is now still controversial.This article reviews the research progress of oral anticoagulant therapy in patients with non-valvular atrial fibrillation complicated with end-stage renal disease.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Bariatric and metabolic surgery has been in China for more than 30 years, which has developed rapidly. However, it can be predicted that there will be many opportunities and challenges in the future development of bariatric and metabolic surgery, including the replacement of classic surgical methods, the guarantee of surgical safety, the brave exploration of new surgical methods, the decisive abandonment of bad surgical methods, the implementation of surgical standardization, and the breakthrough of basic and clinical research all mean more efforts. With the continuous rise of the incidence rate of metabolic syndrome and the continuous improvement of people′s health needs, these opportunities and challenges are particularly significant. Bariatric and metabolic surgery will also play a crucial role in overcoming obesity and metabolic diseases.

To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. A cell model of colitis was established by co-culture of human colon cancer cell line Caco-2 and human monocyte cell line THP-1. The colitis model cells were treated with metformin at concentration of for Flow cytometry was used to detect Caco-2 cell apoptosis, and Western blotting was used to detect the protein expression of tight junction proteins and endoplasmic reticulum stress-related proteins. After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05). In addition, the expression levels of endoplasmic reticulum-related proteins glucose regulated protein (GRP) 78, C/EBP homologous protein (CHOP) and caspase-12, as well as the phosphorylation level of PRKR-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) decreased (all <0.05). Metformin may alleviate the intestinal epithelial barrier damage in colitis by reducing intestinal epithelial cell apoptosis and increasing the expression of tight junction proteins, which may be associated with the inhibition of endoplasmic reticulum stress-induced apoptotic pathway.
Apoptosis ; Caco-2 Cells ; Colitis, Ulcerative ; Endoplasmic Reticulum Stress ; Humans ; Metformin/pharmacology*

Objective To observe the clinical efficacy of HE’s needling method (three ways for unblocking) in treating mild simple obesity due to dampness from spleen deficiency.Method Forty eligible subjects with mild simple obesity due to dampness from spleen deficiency were randomized into group A and group B, 20 cases in each group. Group A was intervened by mild unblocking method plus intensive unblocking method from HE’s needling method, and group B was by mild unblocking method plus warm unblocking method. The obesity-related indexes were observed before and after treatment, and the clinical efficacies were compared.Result The body weight and Body Mass Index (BMI) were significantly changed after intervention in the treatment group (P<0.05). The body weight was significantly changed after treatment in the control group (P<0.05). After treatment, there were no significant differences in comparing the obesity-related indexes (body weight, BMI, waist circumference, hip circumference, and waist-hip ratio) between the two groups (P>0.05). The total effective rate was 55.0% in the treatment group versus 10.0% in the control group, and the difference was statistically significant (P<0.01).Conclusion HE’s needling method is effective in treating mild simple obesity due to dampness from spleen deficiency, and mild unblocking method plus intensive unblocking method can produce a more significant efficacy compared to mild unblocking method plus warm unblocking method.

OBJECTIVEThe aim of this study was to investigate the value of free anterolateral thigh myocutaneous flap (ALTMF) and computed tomography angiography (CTA) for the reconstruction of mouth-floor defects after the resection of middle-late stage carcinoma of the mouth floor.

METHODSSixteen cases of middle-late stage carcinomas of the mouth floor underwent radical resection, and mouth-floor and tongue defects were reconstructed with ALTMF. CTA was applied to plan the lateral circumflex femoral artery (LCFA) and its perforating vessel, which was verified during the operation.

RESULTSThe position of the perforating vessel in the operation was fully consistent with that designed by the preoperative CTA. All 16 flaps completely survived. The appearance and function of all cases were both satisfactory. All donor sites were primarily closed and healed without functional morbidity. During the follow-up period of 6-36 months, 15 cases survived with acceptable aesthetic and functional results in mouth floor and tongue reconstruction, except for 1 case (T4N2M0) that died of metastasis carcinoma 10 months after operation.

CONCLUSIONCTA can accurately locate the LCFA and artery perforator. Preoperative perforator planning using CTA in ALTMF transplantation is a reliable and useful method thatresults in safe operation with optimal outcome. The ALTMF is an ideal choice for the reconstruction of soft tissue defects after the resection of middle-late staie carcinoma of the mouth floor

Angiography ; Carcinoma ; Free Tissue Flaps ; Humans ; Mouth Floor ; Myocutaneous Flap ; Patient Care Planning ; Reconstructive Surgical Procedures ; Thigh ; Tomography ; Tongue

OBJECTIVEThis study aims to evaluate the effect of customized titanium mesh, which was designed by mirror imaging and rapid prototyping technique, with Medpor applied for orbital fracture with enophthalmos.

METHODSOrbital axial, coronal, and sagittal CT scan, and three-dimension CT examination were performed routinely in. 18 cases of orbital fracture with enophthalmos preoperatively. Based on the CT data, prosthesis model was designed by reverse engineering and rapid prototyping technique. The customized titanium mesh and Medpor were applied for orbital reconstruction and enophthalmos correction. Orbital reduction and globe projection were evaluated by postoperative CT scan and clinical follow-up visits.

RESULTSCT scans revealed that the customized titanium mesh with Medpor had great accuracy to reconstruct the orbital fracture and correct the enophthalmos in all patients without serious complications. The eye and facial appearance and function recovered significantly. No serious complication occurred in the operation and after operation.

CONCLUSIONThe customized titanium mesh, based on mirror imaging and rapid prototyping technique, can accurately reconstruct the orbital fractures with enophthalmos. The application of Medpor can effectively correct enophthalmos and eyeball mobility malformation.

Enophthalmos ; therapy ; Facial Bones ; Humans ; Orbit ; Orbital Fractures ; surgery ; Polyethylenes ; Postoperative Period ; Prostheses and Implants ; Reconstructive Surgical Procedures ; Surgical Mesh ; Titanium ; Tomography, X-Ray Computed