Conversion to thoracotomy during minimally invasive esophagectomy: Retrospective analysis in a single center / 中国胸心血管外科临床杂志

@#Objective     To explore the causes of conversion to thoracotomy in patients with minimally invasive esophagectomy (MIE) in a surgical team, and to obtain a deeper understanding of the timing of conversion in MIE. Methods     The clinical data of patients who underwent MIE between September 9, 2011 and February 12, 2022 by a single surgical team in the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. The main influencing factors and perioperative mortality of patients who converted to thoracotomy in this group were analyzed. Results     In the cohort of 791 consecutive patients with MIE, there were 520 males and 271 females, including 29 patients of multiple esophageal cancer, 156 patients of upper thoracic cancer, 524 patients of middle thoracic cancer, and 82 patients of lower thoracic cancer. And 46 patients were converted to thoracotomy for different causes. The main causes for thoracotomy were advanced stage tumor (26 patients), anesthesia-related factors (5 patients), extensive thoracic adhesions (6 patients), and accidental injury of important structures (8 patients). There was a statistical difference in the distribution of tumor locations between patients who converted to thoracotomy and the MIE patients (P<0.05). The proportion of multiple and upper thoracic cancer in patients who converted to thoracotomy was higher than that in the MIE patients, while the proportion of lower thoracic cancer was lower than that in the MIE patients. The perioperative mortality of the thoracotomy patients was not significantly different from that of the MIE patients (P=1.000). Conclusion     In MIE, advanced-stage tumor, anesthesia-related factors,extensive thoracic adhesions, and accidental injury of important structures are the main causes of conversion to thoracotomy. The rate varies at different tumor locations. Intraoperative conversion to thoracotomy does not affect the perioperative mortality of MIE.

Mechanism of white matter lesion in patients with CADASIL / 国际脑血管病杂志

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a common hereditary cerebral small vessel disease, and white matter lesion is its classic pathological feature. MRI showed T 2 white matter hyperintensity, its pathogenesis is complex, and the effective preventive measures are still lacking. This article reviews the possible mechanism of white matter lesion in patients with CADASIL, and provides new ideas for clinical alleviation of white matter lesion and improvement of prognosis.

Establishment and evaluation of rabbit model of closed tibial fracture / 中国骨伤

OBJECTIVE@#To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture.@*METHODS@#The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation.@*RESULTS@#Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing.@*CONCLUSION@#The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.

Associations between plasma n-3 polyunsaturated fatty acids and gestational diabetes mellitus in the second trimester / 中华预防医学杂志

Objective: To examine the associations between plasma n-3 polyunsaturated fatty acids (PUFAs) in the second trimester and gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods: Based on data from the Tongji-Shuangliu Birth Cohort enrolled from 2017 to 2019 in the Shuangliu Maternal and Child Health Hospital, it conducted a case-control study among 269 GDM cases who were diagnosed by 75 g oral glucose tolerance test, and 538 non-GDM controls matched at a 1∶2 ratio on maternal age and gestational weeks. The age range of the 807 women was 18-40 years. Fasting plasma n-3 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester (24-28 weeks). Participants were categorized into quartiles (Q1-Q4) of plasma n-3 PUFAs based on distributions in the control group. Conditional logistic regression models were applied to estimate the associations between plasma n-3 PUFAs and GDM. Results: The median (interquartile) relative concentrations of plasma n-3 PUFA C22∶5n-3 was significantly lower in women with GDM 0.87 (0.72, 1.07) compared with women without GDM 0.94 (0.75, 1.19)(P=0.001). Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM, with an OR (95%CI) of 0.75 (0.62-0.90) for each SD increase of relative concentration. Compared with the Q1 group, the OR values and 95%CIs of Q2, Q3, and Q4 groups were 0.97 (0.62-1.51), 0.72 (0.45-1.15), and 0.54 (0.32-0.90), respectively (Ptrend<0.05). However, there were no significant associations of C18∶3n-3, C20∶5n-3, C22∶6n-3, and total n-3 PUFAs with GDM. Conclusion: Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM during the second trimester.

A comparative study on the clinical effects of hip arthroplasty through direct anterior approach in lateral decubitus in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia / 中华地方病学杂志

Objective:To compare the clinical effects of hip arthroplasty through direct anterior approach (DAA) in lateral decubitus in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia.Methods:The prospective study method was used to select the patients who needed hip arthroplasty in the Fourth Department of Orthopedics, the Second Affiliated Hospital of Harbin Medical University from January 2015 to December 2019. All of them were operated with lateral decubitus DAA. According to the inclusion criteria, they were divided into Kacshin-Beck disease hip osteoarthritis group (group A) and congenital acetabular dysplasia hip osteoarthritis group (group B). Hip Harris score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS) score were conducted, and hip abduction angle and flexion angle were measured before surgery, 3, 14 days and 1, 3, and 12 months after surgery.Results:Nineteen and twenty-two patients were included in group A and group B, respectively. All patients successfully completed the surgery. There was no significant difference in Harris score between the two groups before surgery, 3, 14 days, and 1, 12 months after surgery ( P > 0.05). There were no significant differences in WOMAC score, VAS score, hip abduction angle and hip flexion angle between the two groups before surgery and each time point after surgery ( P > 0.05). In the same group, there were significant differences in Harris score, WOMAC score, VAS score, hip abduction angle and hip flexion angle at different time points ( P < 0.001). All postoperative indicators were significantly improved compared with those before surgery. Conclusions:There is no significant difference in the clinical effects of hip arthroplasty through lateral decubitus DAA in the treatment of hip osteoarthritis caused by Kaschin-Beck disease and congenital acetabular dysplasia. This surgical method has good therapeutic effect on both types of hip osteoarthritis.

Clinicopathological characteristics and prognostic factors analysis of patients with esopha-geal cancer / 中华消化外科杂志

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

Prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer using 99Tc m-3PRGD 2 imaging in comparison to 18F-FDG imaging / 中华核医学与分子影像杂志

Objective:To evaluate the value of 99Tc m-hydrazinonicotinamide-(poly-(ethylene glycol)) 4-E((poly-(ethylene glycol)) 4-c((Arg-Gly-Asp)fK)) 2 (3PRGD 2) imaging on predicting pathological complete response (pCR) outcomes to neoadjuvant chemotherapy (NAC) in patients with breast cancer and to compare it with 18F-FDG imaging. Methods:From October 2017 to October 2019, 41 patients (age: (61.5±7.8) years) who were diagnosed with stage Ⅱ and Ⅲ breast cancer and planned to receive preoperative NAC in the First Affiliated Hospital of Fujian Medical University and Xiehe Affiliated Hospital of Fujian Medical University were prospectively enrolled. All patients underwent both 99Tc m-3PRGD 2 and 18F-FDG imaging before NAC (baseline), and after the first and the fourth NAC cycle. The tumor/background ratio (T/B; 99Tc m-3PRGD 2) and SUV max ( 18F-FDG) in breast tumors and axillary lymph node (ALN) metastases were separately calculated. The relative T/B changes (ΔT/B 1, ΔT/B 2) and SUV max changes (ΔSUV max1, ΔSUV max2) after the first and the fourth NAC cycle compared to baseline were obtained. Patients underwent surgery after NAC and the pathology was used as the gold standard to determine whether patient achieved pCR. The predictive performance of ΔT/B and ΔSUV max regarding the identification of pCR or non-pCR was evaluated by using ROC analysis and the AUCs were compared by Delong test. Results:Of 41 patients, 13 (31.7%) were achieved pCR after NAC. For breast tumors, the AUCs of ΔT/B 1, ΔT/B 2, ΔSUV max1 and ΔSUV max2 were 0.827 ( P=0.001), 0.687 ( P=0.057), 0.859 ( P<0.001) and 0.713 ( P=0.030) respectively, and the AUCs of ΔT/B 1 and ΔSUV max1 had no significant difference ( z=0.33, P=0.740). For ALN metastases, the AUCs of ΔT/B 1, ΔT/B 2, ΔSUV max1 and ΔSUV max2 were 0.859 ( P=0.002), 0.778 ( P=0.014), 0.572 ( P=0.523) and 0.802 ( P=0.007) respectively, and the AUC of ΔT/B 1 was significantly higher than that of ΔSUV max1 ( z=2.10, P=0.035). Conclusion:The early relative changes of breast tumors and ALN metastases in 99Tc m-3PRGD 2 imaging during NAC can offer predictive information for pCR to NAC in patients with breast cancer, and early relative changes of ALN metastases in 99Tc m-3PRGD 2 imaging may have a higher predictive value for pCR than 18F-FDG imaging.

Comparison of efficacy of femoral tunnel creation with figure-of-four position and traditional knee hyperflexed position for arthroscopic anterior cruciate ligament reconstruction using tendon autograft / 中华创伤杂志

Objective:To compare the efficacy of arthroscopic anterior cruciate ligament reconstruction using tendon autograft with figure-of-four position and traditional knee hyperflexed position for femoral tunnel creation.Methods:A retrospective case series study was conducted to analyze the clinical data of 46 patients with ACL injury admitted to Second Affiliated Hospital of Harbin Medical University from August 2019 to October 2019, including 26 males and 20 females; aged 24-40 years [(31.1±7.5)years]. All patients underwent arthroscopic ACL reconstruction using tendon autograft. The femoral tunnel was created with figure-of-four position in 21 patients (figure-of-four position group) and with traditional knee hyperflexed position in 25 patients (knee hyperflexed position group). The operation time was compared between the two groups. The center position, length and angle of femoral tunnel were evaluated and measured by three dimensional CT reconstruction and Bernard quadrant method at 8 weeks postoperatively. The knee function was assessed by knee Lysholm score preoperatively, at 8 weeks and at 1 year postoperatively. Complications were observed as well.Results:All patients were followed up for 2-20 months [(15.3±2.1)months]. The operation time was (28.5±2.6)minutes in figure-of-four position group, significantly less than (39.5±2.4)minutes in knee hyperflexed position group ( P<0.05). The tunnel center position was located at (27.1±1.4)% and (25.1±2.6)% within the Bernard quadrant in figure-of-four position group, similar with (28.1±2.8)% and (26.1±3.1)% in knee hyperflexed position group (all P>0.05). Total tunnel length and thick tunnel length were (42.1±2.4)mm and (34.1±2.4)mm in figure-of-four position group, significantly longer than (38.2±2.5)mm and (31.1±2.7)mm in knee hyperflexed position group (all P<0.05). The coronal plane angle of the tunnel was (41.1±2.4)° in figure-of-four position group, significantly smaller than (47.5±2.6)° in knee hyperflexed position group ( P<0.05). The sagittal plane angle of the tunnel was (42.1±1.4)° in figure-of-four position group, significantly greater than (37.1±1.8)° in knee hyperflexed position group ( P<0.05). Figure-of-four position group showed the knee Lysholm score of (53.4±5.2)points preoperatively, (97.1±1.4)points at 8 weeks postoperatively and (98.3±2.3)points at 1 year postoperatively. Knee hyperflexed position group showed the knee Lysholm score of (54.3±7.4)points preoperatively, (97.1±1.6)points at 8 weeks postoperatively and (98.1±1.3)points at 1 year postoperatively. The knee Lysholm score did not differ significantly between the two groups (all P>0.05), but the knee function was significantly improved in both groups when compared with that before the operation (all P<0.05). There were 1 patient with femoral tunnel fracture, one with injury to the medial condylar cartilage and one with injury to the posterior root of lateral meniscus in knee hyperflexed position group, while no above-mentioned complications occurred in figure-of-four position group ( P<0.05). Conclusion:Arthroscopic ACL reconstruction using tendon autograft with femoral tunnel creation through figure-of-four position and traditional knee hyperflexed position can both contribute knee functional recovery, but the figure-of-four position has the advantages of short operation time, accurate tunnel positioning, favorable length and angle of the tunnel and less complications.

27-P-CAUA induces apoptosis and mitochondrial autophagy in breast cancer cells by inhibiting HER2/PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of 27-P-coumayl-ursolic acid (27-P-CAUA), the active ingredient in triterpenoids from the leaves of Ilex latifolia Thunb, against breast cancer cells and explore the underlying mechanism.@*METHODS@#CCK-8 assay was used to assess the changes in viability of breast cancer HCC-1806 cells after 27-P-CAUA treatment for 24, 48, or 72 h. The inhibitory effect of 27-P-CAUA on proliferation of the cells was determined by clonogenic assay. JC-1 was used to detect the changes in mitochondrial membrane potential and flow cytometry was performed for analyzing cell apoptosis following 27-P-CAUA treatment. Immunofluorescence assay was used to observe the expression of cl-caspase-3 and P62 in the treated cells. Western blotting was performed to observe the effect of 27-P-CAUA and chloroquine pretreatment on the expressions of LC3I/II, P62 and HER2 signaling pathway proteins in the cells.@*RESULTS@#The results of CCK-8 and clonogenic assays showed that 27-P-CAUA treatment significantly inhibited the proliferation of HCC-1806 cells (P < 0.01) with IC50 values of 81.473, 48.392 and 18.467 μmol/L at 24, 48, and 72 h, respectively. 27-P-CAUA treatment also caused obvious changes in mitochondrial membrane potential (P < 0.01) and induced cell apoptosis in HCC-1806 cells with a 3.34% increase of the early apoptosis rate. Immunofluorescence assay revealed a significant increase of cl-caspase3 expression in 27-P-CAUA-treated HCC-1806 cells, and treatment with 40 μmol/L 27-P-CAUA resulted in significant cell apoptosis (P < 0.01). 27-P-CAUA obviously reduced the expression of LC3II, caused P62 degradation and induced autophagy in HCC-1806 cells. Chloroquine pretreatment obviously blocked the autophagy-inducing effect of 27-P-CAUA. 27-P-CAUA treatment also inhibited the phosphorylation of HER2 and AKT proteins and progressively lowered the expressions of HER2 and phosphorylated AKT protein in HCC-1806 cells (P < 0.01).@*CONCLUSION@#27-P-CAUA can inhibit the proliferation and induce mitochondrial autophagy and apoptosis of HCC-1806 cells by inhibiting the HER2/PI3K/AKT signaling pathway.

Predictors and Dynamic Nomogram to Determine the Individual Risk of Malignant Brain Edema After Endovascular Thrombectomy in Acute Ischemic Stroke

Background@#and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). @*Methods@#We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. @*Results@#MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of 0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). @*Conclusions@#Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

Galectin-3 Derived from HucMSC Exosomes Promoted Myocardial Fibroblast-to-Myofibroblast Differentiation Associated with β-catenin Upregulation

Background and Objectives@#Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. @*Methods@#and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. @*Conclusions@#HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.

Genetic testing and prenatal diagnosis for a pedigree affected with tuberous sclerosis complex / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for Chinese pedigree affected with tuberous sclerosis complex (TSC).@*METHODS@#The proband and his family members were subjected to Sanger sequencing for variants of the TSC1 and TSC2 genes.@*RESULTS@#The proband was found to harbor a c.2837+1dupG splicing variant at a donor site of the TSC2 gene. The same variant was not found among his family members and the fetus during his mother's subsequent pregnancy.@*CONCLUSION@#The c.2837+1dupG splicing variant of the TSC2 gene has probably predisposed to the TSC in this pedigree. Above finding has enriched the spectrum of pathogenic variants associated with this disease.

Application value of different surgical approaches in the radical resection of Siewert type Ⅱ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the application value of different surgical approaches in the radical resection of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 84 patients with Siewert Ⅱ AEG who were admitted to the Fourth Hospital of Hebei Medical University from March 2018 to March 2019 were collected. There were 65 males and 19 females, aged from 43 to 82 years, with a median age of 66 years. Of 84 patients, 24 cases undergoing radical resection of AEG via abdominal transhiatal approach (TH) were allocated into TH group, 32 cases undergoing radical resection of AEG via left thoracic approach (Sweet) were allocated into Sweet group, 28 cases undergoing radical resection of AEG via right thoracoabdominal approach (RTA) were allocated into RTA group. Observation indicators: (1) surgical and postoperative conditions of Siewert Ⅱ AEG patients in the 3 groups; (2) postoperative complications of Siewert Ⅱ AEG patients in the 3 groups. (3) Follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect postoperative life quality, tumor recurrence and survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the ANOVA. Measurement data with skewed distribution were represented as M (range), comparison among multiple groups was analyzed using the Kruskal-Wallis H test, and comparison between two groups was analyzed using the Dunn Bonferroni test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Surgical and postoperative conditions of Siewert Ⅱ AEG patients in the 3 groups: the operation time for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 216 minutes (range, 190-230 minutes), 174 minutes (range, 152-185 minutes) and 295 minutes (range, 261-337 minutes), respectively, showing a significant difference among the 3 groups ( H=57.977, P<0.05). There were significant differences between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P<0.05). There was also a significant difference between the Sweet group and the RTA group ( P<0.05). The volume of intraoperative blood loss for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 150 mL (range, 100-163 mL), 150 mL (range, 150-200 mL) and 200 mL (range, 150-263 mL), respectively, showing a significant difference among the 3 groups ( H=11.097, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 15 (range, 9-19), 17 (range, 10-21) and 30 (range, 24-40), respectively, showing a significant difference among the 3 groups ( H=29.775, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of thoracic lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 0, 2 (range, 1-3) and 6 (range, 3-9), respec-tively, showing a significant difference among the 3 groups ( H=48.140, P<0.05). There were significant differences between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P<0.05). There was also a significant difference between the Sweet group and the RTA group ( P<0.05). The number of abdominal lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 15 (range, 9-19), 12 (range, 8-19), and 24 (range, 17-35), respectively, showing a significant difference among the 3 groups ( H=18.149, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of positive lymph node for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 2 (range, 0-3), 0 (range, 0-3), and 5 (range, 1-6), respectively, showing a significant difference among the 3 groups ( H=7.729, P<0.05). There was no significant difference between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P>0.05). There was a significant difference between the Sweet group and the RTA group ( P<0.05). The time to postoperative first flatus of Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 3 days (range, 3-4 days), 3 days (range, 3-4 days), and 4 days (range, 3-5 days), respectively, showing no significant difference among the 3 groups ( H=3.125, P>0.05). The duration of postoperative hospital stay for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 16 days (range, 14-17 days), 14 days (range, 12-15 days), and 19 days (range, 18-21 days), respectively, showing a significant difference among the 3 groups ( H=35.244, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). (2) Postoperative complications of Siewert Ⅱ AEG patients in the 3 groups: there were 6, 6, 11 Siewert type Ⅱ AEG patients of the TH group, Sweet group and RTA group with cardiopulmonary complication, respectively, 1, 1, 2 patients with anastomotic leakage and 1, 0, 1 patients with AEG-related death, showing no significant difference in the above indicators among the 3 groups ( χ2=3.263, 0.754, 1.595, P>0.05). (3) Follow-up: 78 of 84 Siewert type Ⅱ AEG patients were followed up for 9.0 to 24.0 months, with a median follow-up time of 16.6 months. Cases with reduced respiratory function at postoperative 3 months for the TH group, Sweet group and RTA group were 4, 3, 5, respectively. Cases with gastroesophageal reflux at postoperative 3 months for the 3 groups were 3, 6, 7, respectively. Cases with weight loss at post-operative 3 months for the 3 groups were 3, 2, 4, respectively. There was no significant difference in the above indicators among the 3 groups ( χ2=1.009, 1.107, 1.112, P>0.05). Cases tumor recurrence and metastasis in the TH group, Sweet group and RTA group were 5, 7, 4, cases who survived at postoperative 1 year in the 3 groups were 19, 24, 25, respectively. There was no significant difference in the above indicators among the 3 groups ( χ2=0.897, 1.261, P>0.05). Conclusion:RTA appiled in Siewert type Ⅱ AEG patients has a longer postoperative operation time, increased intra-operative blood loss and longer hospital stay, while has better advantages in lymph node dissection.

Mechanism of Chinese Medicine in Induction of Apoptosis of Lung Cancer Cells： A Review / 中国实验方剂学杂志

Lung cancer， a malignancy with high incidence rate and mortality rate， is a major threat to human life and health. At present， the common methods for the treatment of lung cancer include surgical resection， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， but these methods generally have the problems of severe toxic/side effect and high treatment cost. Traditional Chinese medicine（TCM） has a history of more than 2 000 years of application in China and has its unique advantages in the treatment of tumors. Modern pharmacological experiments have found that TCM can inhibit tumor growth， prolong patients' survival， and improve clinical symptoms and patients' quality of life by inducing tumor cell apoptosis， inhibiting tumor angiogenesis， and reducing tumor cell drug resistance. Apoptosis is a process of spontaneous programmed cell death， which is closely related to the occurrence and development of the tumor. Studies have shown that many Chinese medicines can inhibit the development of lung cancer by inducing apoptosis. This study searched， analyzed， and summarized the available papers on the mechanism of TCM in the treatment of lung cancer by inducing apoptosis. It is found that Chinese medicine induces lung cancer cell apoptosis mainly by regulating apoptosis-related factors and apoptosis-related signaling pathways ［inhibitor of apoptosis proteins （IAPs）， B cell lymphoma-2 （Bcl-2）， p53 protein， the second mitochondria-derived activator of caspase （SMAC）/direct IAP-binding protein with low isoelectric point （DIABLO）， extrinsic apoptotic pathway， endogenous mitochondrial pathway， Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. In addition， the Wnt/β-catenin/survivin signaling pathway and the Notch signaling pathway also play an important role in inducing apoptosis.

Role of hsa_circ_0081596 in oxygen-glucose deprivation and restoration injury to human neurons / 中华麻醉学杂志

Objective:To evaluate the role of hsa_circ_0081596 in oxygen-glucose deprivation and restoration (OGD/R) injury to human neurons. Methods:SK-N-SH cells were cultured and the cells within 5 generations were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), OGD/R group (group O), OGD/R+ siRNA group (group S) and OGD/R+ siRNA negative control group (group I). The cells in C group were cultured under normal conditions of 37 ℃ and 5% CO 2.The cells in group O were placed in 6- or 96-well plates until they were completely attached to the wall, and then subjected to oxygen-glucose deprivation for 4 h, followed by restoration of oxygen-glucose for 24 h. In group S and group I, the cells were transfected with hsa_circ_0081596 siRNA and its negative control, respectively, and 72 h later OGD/R model was established.The expression of hsa_circ_0081596 and mitochondrial fission protein 1 (Fis1) mRNA was detected using quantitative real-time polymerase chain reaction.The expression of Fis1 was determined by Western blot, the cell survival rate was determined by CCK-8 assay and the apoptosis rate was determined by flow cytometry. Results:Compared with group C, the expression of hsa_circ_0081596, Fis1 and its mRNA was significantly up-regulated, the cell survival rate was decreased, and the apoptosis rate was increased in group O ( P<0.05). Compared with group O, the expression of hsa_circ_0081596 and Fis1 was significantly down-regulated, the cell survival rate was increased and the apoptosis rate was decreased in group S, and the expression of hsa_circ_0081596 and Fis1 was significantly up-regulated, the cell survival rate was decreased and the apoptosis rate was increased in group I ( P>0.05). Conclusion:hsa_circ_0081596 is involved in the pathophysiological mechanism of OGD/R through up-regulating the expression of Fis1 in human neurons.

Galectin-3 Derived from HucMSC Exosomes Promoted Myocardial Fibroblast-to-Myofibroblast Differentiation Associated with β-catenin Upregulation

Background and Objectives@#Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study. @*Methods@#and Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS＋hucMSC-ex, LPS＋negative control-siRNA-ex (NC-ex), or LPS＋ Galectin-3-siRNA-ex (si-ex) in vitro. The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex in vivo. Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. β-catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and β-catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities. @*Conclusions@#HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased β-catenin levels.

Content Determination and Cluster Analysis of 7 Kinds of Triterpenes in Poria cocos from Different Habitats / 中国药房

OBJECTIVE：To establish a method for th e content determination of 7 kinds of triterpenoids in Poria cocos ，and to compare the differences of the above components in P. cocos from different habitats ，so as to provide reference for the quality control of P. cocos . METHODS ：Using 36 batches of P. cocos from different habitats as samples ，HPLC method was used for content determination of dehydrotomorphic acid ， polyporhinic acid C ， 3-epidehydrotomorphic acid ， 3-O-acetyl-16 α-hydroxy-hydrogenolysaccharic acid ，dehydrotomorphic acid ，pachymic acid and dehydrotrametenolic acid. The column was performed on Thermo Acclaim 120 C18 with mobile phase consisted of acetonitrile-phosphoric acid water （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 210 nm. The column temperature was 30 ℃，and the injection volume was 20 μL. SPSS 21.0 statistical software was used for cluster analysis of 36 batches of P. cocos from different habitats. RESULTS ： The linearity of 7 triterpenoids was good in the range of their mass concentration （all r≥0.999 0）；average recoveries were 96.74％-104.04％（RSD＝0.54％-1.55％，n＝6）. RSDs of precision ，and reproducibility stability （24 h）tests were all lower than 3.0％（n＝6）. RSD of durability test was lower than 5.0％（n＝2）. There were some differences in the single content of 7 indicator components among samples from different habitats ，but the total content difference was not obvious （the total content of most samples was in the range of 1.3-1.9 mg/g）. After cluster analysis ，36 batches of sample were clustered into 5 categories，i.e. S 27 was clustered into class Ⅰ；S30 and S 34 were clustered into class Ⅱ；S2，S8 and S 9 were clustered into class Ⅲ；S10，S11，S12 and S 14 were clustered into class Ⅳ；and the remaining 26 batches of samples were clustered into class Ⅴ. CONCLUSIONS ：The method is simple ，and has good precision ，repeatability and durability. It can be used for the simultaneous determination of above 7 components in P. cocos . There has no significant difference in the quality of P. cocos from different habitats. The content of P. cocos in most producing areas is uniform in content and stable in quality ，only a few of them are different. Δ 基金项目 ：国家重点研发计划中医药现代化研究重点专项

Combination of Evodiamine with Berberine Reveals a Regulatory Effect on the Phenotypic Transition of Colon Epithelial Cells Induced by CCD-18Co / 中国医学科学杂志(英文版)

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. This study aimed to explore the effect of combination of evodiamine with berberine (cBerEvo) on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts, as well as the involved mechanisms.Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18Co, a human colon myofibroblast line, to induce epithelial-mesenchymal transition. Phase contrast microscope was used to observe the morphological changes. Epithelial-mesenchymal transition markers including E-cadherin, vimentin and alpha-smooth muscle actin (α-SMA) were observed with immunofluorescence microscopy. Migration was assessed by wound healing assay. Western blotting was used to detect the expressions of E-cadherin, vimentin, α-SMA, Snail, ZEB1 and Smads. Results In contrast to the control, the tumor-associated fibroblasts-like CCD-18Co cells induced down-regulation of E-cadherin and up-regulation of vimentin, α-SMA, Snail and ZEB1 (<0.05), and promoted migration of HCoEpiCs (<0.05), with over expression of Smads including Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 (<0.05), which were abolished by a transforming growth factor-β (TGF-β) receptor inhibitor LY364947 and by cBerEvo in a concentration dependent manner. In addition, cBerEvo-inhibited ratios of p-Smad2/Smad2 and p-Smad3/Smad3 were also dose dependent.Conclusion The above results suggest that cBerEvo can regulate the differentiation of colon epithelial cells induced by CCD-18Co through suppressing activity of TGF-β/Smads signaling pathway.

Research progress of epidemiology and non-pharmaceutical intervention of Alzheimer's disease: an update / 中华老年医学杂志

A community-based,comprehensive intervention approach can not only improve the condition of AD patients from cognitive,memory and mood,improve the quality of life,stimulate of nerve cell growth and self-care,but also reduce the pressure on the patient's family and caregivers,and on society.This paper mainly focuses on the current status of AD epidemiology and the nonpharmaceutical interventions at home and abroad,and provides a reference for improving the quality of life of the elderly.

A feasibility study of fetal intelligent navigation echocardiography in the prenatal screening of right aortic arch with left-sided ductus arteriosus / 中华超声影像学杂志

Objective:To investigate the feasibility of applying Fetal Intelligent Navigation Echocardiography (FINE) combined with Virtual Intelligent Sonographer Assistance (VIS-Assistance ?) in the prenatal screening of right aortic arch (RAA) with left-sided ductus arteriosus (LDA). Methods:A total of 32 fetuses with RAA and LDA during middle and late pregnancy in Zhejiang University Medical College Affiliated Sir Run Run Shaw Hospital from Jauary 2018 to Jauary 2020 were included in this retrospective study, and the datas about fetal cardiac three-dimensional volume were analyzed. The time-space correlation imaging (STIC) volume data were collected by using FINE by Senior doctor A. The two diagnostic elements of the transverse aortic arch on the right side of the trachea and the "U" -shaped vascular ring, as well as the three-vessel tracheal diagnostic section were obtained by low-aged doctor B and middle-aged doctor C by using VIS-Assistance ? technology. And then the detection rates of diagnostic sections and diagnostic elements for fetuses with RAA and LDA were calculated. The postpartum outcomes of fetuses with RAA and LDA were followed up. Results:Thirty-two fetuses were included in the study after excluding 2 cases due to the poor quality images, and the datas about fetal cardiac three-dimensional volume of the 32 fetuses were analyzed. The detection rate of one diagnostic element (the aortic arch on the right side of the trachea) were 84.4% vs 87.5% before VIS-Assistance ?, and 93.8% vs 93.8% after VIS-Assistance ? for each doctor B and doctor C , respectively. Another diagnostic element ( "U" -shaped vascular ring) were 78.1% vs 87.3% before VIS-Assistance ?, and 90.6% vs 90.6% after VIS-Assistance ? for doctor B and doctor C, respectively. But no significant difference was found before and after VIS-Assistance ? between the two each doctors(all P>0.05). The detection rate of three-vascular tracheal diagnosis view were 65.6% vs 71.9% before VIS-Assistance ? and 84.4% vs 87.5% after VIS-Assistance ? for doctor B and doctor C, respectively. There was significant difference before and after VIS-Assistance ? of doctor C( P<0.05). The scores of image quality after VIS-Assistance ? were significantly higher than that before VIS-Assistance ? for doctor B and doctor C, respectively [3(2.5, 3) vs 3.25(3.0, 3.5), and 3(2.5, 3.5) vs 3.5(3.0, 3.5)]. The agreement between two doctors performing VIS-Assistance ? was investigated using Bland-Altman analysis and the result showed that within 95% of the differences fall in the agreement interval. No obvious clinical symptoms of compression were found in 32 neonates after follow-up. Conclusions:The application of FINE combined with VIS-Assistance ? technology can easily and reliably obtain the key diagnostic view of RAA with LDA (three-vessel and tracheal view), and clearly display all diagnostic elements, having high repeatability and stability. VIS-Assistance ? technology can improve the detection rate and image quality even if the doctor was lack of experience. So it can be used as an effective supplementary means for prenatal screening of RAA and LDA.