[Prevalence and intervention effect of arteriovenous graft stenosis].

Objective: To evaluate the prevalence, intervention methods and effect of arteriovenous graft (AVG) stenosis. Methods: The clinical data of patients who received AVG in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. The patency rate, prevalence and intervention effect of AVG stenosis were analyzed. Results: A total of 475 patients aged (55.5±11.8) years were included, and there were 193 male cases (40.6%) and 282 female cases (59.4%). The patients were followed up for [M (Q1, Q3)] 19 (12, 30) months, and the primary, assisted primary and secondary patency were 14 (5, 27), 27 (13, 55), and 59 (33, 65) months, respectively. There were 799 access events which needed intervention, with a total standardized intervention rate of 0.90 per patient-year. Totally, 431(53.9%, 431/799) stenosis events occurred in 207 AVG. Among 422 AVG stenosis events with complete clinical data, 57.8% (244/422) were multi-site stenosis and 42.2% (178/422) were single-site stenosis. The most common sites of stenosis were graft-vein anastomosis (47.6%, 340/715), venous outflows (22.7%, 162/715), and puncture zone (20.0%, 143/715). In the 414 stenosis with intact follow-up data, 90.8% (376/414) were treated by balloon angioplasty, 8.5% (35/414) received covered stent insertion, and 0.7% (3/414) were intervened by open surgery. Clinical success rate was 98.1% (406/414). The primary patency time after endovascular treatment was 6 (4, 12) months. Covered stent significantly increased post-intervention primary patency time compared withballoon angioplasty [6 (3, 7) months vs 3 (1, 4) months, P=0.020]. Conclusions: Stenosis is the most common complication of AVG, and the most common sites are graft-vein anastomosis, venous outflows, and puncture zone. Intervention of AVG stenosis has a high clinical success rate, and a relatively low post-intervention patency. Covered stent insertion improves the post-intervention patency of AVG, which has a poor effect using balloon expansion.

[Clinical effects of different types of tissue flaps in repairing the wounds with steel plate exposure and infection after proximal tibial fracture surgery].

Objective: To investigate the clinical effects of different types of tissue flaps in repairing the wounds with steel plate exposure and infection after proximal tibial fracture surgery. Methods: A retrospective observational study was conducted. From January 2015 to December 2021, 11 patients with steel plate exposure and infected wounds after proximal tibial fracture surgery who met the inclusion criteria were admitted to Jiangxi Provincial General Hospital of Armed Police, including 9 males and 2 females, aged 26 to 61 years. The wounds were located on the lateral side of the proximal leg in 5 cases, on the medial side of the proximal leg in 2 cases, and on the medial side of the proximal leg and the anterior tibia below the knee in 4 cases. After debridement, the wound area was 14 cm×6 cm-22 cm×11 cm. The wounds were repaired with different types of tissue flaps, and the steel plates were removed immediately if necessary, according to the infection around the steel plates. The reverse anterolateral thigh myocutaneous flap pedicled with the muscle containing the terminal small branch of the descending branch of the lateral circumflex femoral artery was used in 3 cases; the medial gastrocnemius muscle flap combined with the medial half of soleus muscle flap was used in 6 cases, and the lateral gastrocnemius muscle flap combined with the anterior tibial muscle flap was used in 2 cases. After the muscle flaps had stable blood supply, the wounds were closed with thin intermediate thickness skin graft from the healthy thigh. The area of myocutaneous flap ranged from 15 cm×7 cm to 18 cm×8 cm, and the area of muscle flap ranged from 6.0 cm×4.0 cm to 18.0 cm×12.0 cm. Among the 3 patients who were treated with reverse anterolateral thigh myocutaneous flap, the wounds of flap donor site on thighs were closed by direct suturing in 2 cases, and the wound in the flap donor site of thigh in 1 case that was not closed after suture was repaired with thin intermediate thickness skin graft from healthy thigh. The incisions in the flap donor sites of 8 cases treated with calf muscle flaps were sutured directly. After surgery, the survivals of tissue flap and skin graft on the muscle flap, wound healing status and wound healing time in recipient sites of tissue flaps, suture site healing in flap donor site, and survival of skin graft were observed and recorded. Whether the steel plate was removed after operation and during follow-up was recorded. During follow-up, the shape and texture of tissue flap, whether the recipient site of tissue flap had redness, swelling, ulceration, or sinus formation were observed, the fracture healing time was recorded. At the last follow-up, the knee joint flexion and extension range of motion was measured and the knee joint function was evaluated according to Hohl's knee joint function evaluation criteria; the plantar flexor muscle strength of ankle joint was measured in 8 patients who were treated with calf muscle flaps for wound repair; the Vancouver scar scale (VSS) was used to evaluate the scar condition in the flap donor site, and whether the scar affected the movement of the affected limbs was observed. Results: Tissue flaps of 11 patients all survived after surgery. The distal end of the reverse anterolateral thigh myocutaneous flaps was necrotic in 1 patient, and the wound was healed after dressing change and grafting with thin intermediate thickness skin from healthy thigh. The distal muscle necrosis of the medial gastrocnemius muscle flap was observed in 2 patients, and the granulation tissue grew well after dressing change. The skin graft on the muscle flap survived well. All the wounds in the recipient sites of tissue flaps were healed, and the healing time was 13 to 42 days after tissue flap transplantation. The suture site of flap donor site healed, and the skin graft survived well. In 1 patient, the steel plate was removed when the wound was repaired with the medial gastrocnemius muscle flap combined with the medial half of soleus muscle flap. One patient still had exudation after 3 weeks of wound repair with the reverse anterolateral thigh myocutaneous flap pedicled with the muscle containing the terminal small branch of the descending branch of the lateral circumflex femoral artery, and the wound was healed after removing the steel plate. The steel plates of the other patients were preserved. During the follow-up of 6-25 months, except for 1 reverse anterolateral thigh myocutaneous flap had bloated pedicle, the other tissue flaps had good appearance and texture. One patient had redness and swelling in the recipient site of the tissue flap at 6 weeks after discharge, and the redness and swelling subsided without recurrence after anti-infection treatment. In 1 patient, repeated rupture and exudation occurred in the recipient site of tissue flap in 3 months after discharge, resulting in sinus tract formation, which was healed after the removing of steel plate. The fracture healing time of patients ranged from 6 to 15 months after injury. At the last follow-up, the knee joint function was evaluated as excellent in 4 cases, good in 6 cases, and poor in 1 case. Among the 8 patients who were treated with calf muscle flaps for wound repair, 7 patients had ankle joint plantar flexor muscle strength of grade Ⅵ, and 1 patient had ankle plantar flexor muscle strength of grade Ⅴ. The VSS scores of scars in the flap donor sites ranged from 2 to 7, and scars did not significantly affect the movement of the affected limbs. Conclusions: The reverse anterolateral thigh myocutaneous flap pedicled with the muscle containing the terminal small branch of the descending branch of the lateral circumflex femoral artery and the gastrocnemius muscle flap combined with soleus muscle flap or anterior tibial muscle flap are the derived types of the commonly used reverse anterolateral thigh myocutaneous flap and gastrocnemius muscle flap. Using them to repair the wounds with steel plate exposure and infection after proximal tibial fracture surgery can not only ensure the smooth operation, but also preserve the steel plate and promote fracture healing as much as possible, without significantly affecting the function of the affected limb.

[Establishment and validation of a predictive clinical model for postoperative surgical site infection in patients with colorectal surgery].

Objective: To investigate the risk factors of surgical site infection (SSI) after colorectal surgery, and to establish and validate a risk prediction model nomogram. Methods: An observational study was conducted to retrospectively collect data of 6527 patients aged ≥16 years who underwent colorectal surgery in 56 domestic hospitals from March 1, 2021 to February 28, 2022 from the national Surgical Site Infection Surveillance network. The incidence of SSI after surgery was 2.3% (149/6527). According to the ratio of 7:3, 6527 patients were randomly divided into the modeling cohort (4568 cases) and the validation cohort (1959 cases), and there was no statistically significant difference between the two datasets (P>0.05). Univariate analysis was performed using t test /Mann-Whitney U test /χ2 test. Multivariate analysis was performed using binary logistic regression to establish a preliminary model and select variables using Lasso analysis to establish an optimized model nomogram. The discrimination and calibration of the model were evaluated by ROC curve, calibration curve, and Hosmer-Lemeshow test. AUC value>0.7 is considered a good discrimination of the model. The Bootstrap method (repeated self-sampling 1000 times) was used to verify the constructed model internally and externally to evaluate the accuracy of the constructed model. Results: Multivariate analysis showed that history of chronic liver disease (OR=3.626, 95%CI: 1.297-10.137, P<0.001) and kidney disease (OR=1.567,95%CI:1.042-2.357,P=0.038), surgical antibiotic prophylaxis (OR=1.564, 95%CI:1.038-2.357,P=0.035), and emergency surgery (OR=1.432,95%CI: 1.089-1.885, P=0.021), open surgery (OR=1.418, 95%CI:1.045-1.924, P=0.042), preoperative stoma (OR=3.310, 95%CI:1.542-7.105,P<0.001), postoperative stoma (OR=2.323,95%CI: 1.537-8.134,P<0.001), surgical incision type above grade II (OR=1.619,95%CI:1.097-2.375,P=0.014), and each unit increase in total bilirubin (OR=1.003,95%CI:-0.994-1.012, P=0.238), alanine aminotransferase (OR=1.006, 95%CI:1.001-1.011,P=0.032), blood urea nitrogen (OR=1.003,95%CI:0.995-1.011,P=0.310), blood glucose (OR=1.024, 95%CI:1.005-1.043,P=0.027), C-reactive protein (OR=1.007, 95%CI:1.003-1.011,P<0.001), length of incision (OR=1.042, 95%CI:1.002-1.087,P=0.031), surgical duration (OR=1.003,95%CI:1.001-1.005,P=0.017), and surgical blood loss (OR=1.001,95%CI: 1.000-1.002,P=0.045) were risk factors for SSI after colorectal surgery. Each unit increase in albumin level (OR=0.969,95%CI:0.941-0.998,P=0.036) was an independent protective factor for SSI after colorectal surgery. The area under the curve of the optimized model obtained by internal and external validation were 0.768 (95%CI: 0.723-0.813) and 0.753 (95%CI: 0.680-0.832), respectively. The predicted value of the calibration curve was basically consistent with the actual value. Conclusions: The risk prediction model for SSI after colorectal surgery constructed in this study has good discrimination and calibration. The nomogram created in this model can provide an evaluation basis for the observed rate and expected event rate of SSI after clinical colorectal surgery.

[Surgical site infection after colorectal surgery in China from 2018 to 2020].

Objective: This study aims to survey the incidence of surgical site infection (SSI) in China and to analyze its risk factors, so as to prevent and control SSI after colorectal surgery. Methods: An observative study was conducted. Based on a program of Chinese SSI Surveillance from 2018 to 2020, the clinical data of all adult patients undergoing colorectal surgery during this time period were extracted. These included demographic characteristics and perioperative clinical parameters. Minors, pregnant women, obstetric or gynecological surgery, urological system surgery, retroperitoneal surgery, resection of superficial soft tissue masses, and mesh or other implants were excluded. A total of 2122 patients undergoing colorectal surgery from 50 hospitals were included, including 1252 males and 870 females. The median age was 63 (16) years and the median BMI was 23 (4.58) kg/m2. The primary outcome was the incidence of SSI within 30 days after colorectal surgery. The secondary outcomes were mortality within 30 days postoperatively, length of ICU stays and postoperative hospital stays, and cost of hospitalization. Patients were divided into the SSI group and non-SSI group based on the occurrence of SSI. Multivariable logistic regression was performed to analyze risk factors of SSI after colorectal surgery, and subgroup analysis was conducted for open and laparoscopic surgery. Results: The incidence of SSI after colorectal surgery was 5.6% (119/2122), including 47 cases (47/119, 39.5%) with superficial incisional infections, 24 cases (24/119, 20.2%) with deep incisional infections, and 48 cases (48/119, 40.3%) with organ/space infections. The occurrence of SSI significantly increased mortality [2.5% (3/119) vs. 0.1%(3/2003), χ2=22.400, P=0.003], the length of ICU stay [0 (1) day vs. 0(0) day, U=131 339, P<0.001], postoperative hospital stay [18.5 (12.8) days vs. 9.0 (6.0) days, U=167 902, P<0.001], and medical expenses [75 000 (49 000) yuan vs. 60 000 (31 000) yuan, U=126 189, P<0.001] (P<0.05). Multivariate analysis revealed that hypertension (OR=1.782, 95%CI: 1.173-2.709, P=0.007), preoperative albumin level (OR=1.680, 95%CI: 1.089-2.592, P=0.019), a contaminated or infected incision (OR= 1.993, 95%CI: 1.076-3.689, P=0.028), emergency surgery (OR=2.067, 95%CI: 1.076-3.972, P=0.029), open surgery (OR=2.132, 95%CI: 1.396-3.255, P<0.001), and surgical duration (OR=1.804, 95%CI: 1.188-2.740, P=0.006) were risk factors for SSI, while preoperative skin preparation (OR=0.478, 95%CI: 0.310-0.737, P=0.001) was a protective factor for SSI. Subgroup analysis was performed on patients undergoing open or laparoscopic surgery. The incidence of SSI in the open surgery group was 10.2%, which was significantly higher than that in the laparoscopic or robotic group (3.5%, χ2=39.816, P<0.001). Subgroup analysis identified that a contaminated or infected incision (OR=2.168, 95%CI: 1.042-4.510, P=0.038) and surgical duration (OR=2.072, 95%CI: 1.171-3.664, P=0.012) were risk factors for SSI after open surgery, while mechanical bowel preparation (OR=0.428, 95%CI: 0.227-0.807, P=0.009) and preoperative skin preparation (OR=0.356, 95%CI: 0.199-0.634, P<0.001) were protective factors for SSI after open surgery. In laparoscopic surgery, diabetes mellitus (OR= 2.292, 95%CI: 1.138-4.617, P=0.020) and hypertension (OR=2.265, 95%CI: 1.234-4.159, P=0.008) were risk factors for SSI. Conclusions: The incidence of SSI after colorectal surgery is 5.6%. Minimally invasive surgery should be selected to reduce the occurrence of postoperative SSI. To prevent the occurrence of SSI after open surgery, skin preparation and mechanical bowel preparation should be performed before the operation, and the duration of the operation should be shortened as much as possible. In the perioperative period, care of patients with hypertension, diabetes, and contaminated or infected incisions should be given particular attention.

[Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing].

Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.

Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9.

The article "Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9, by Z.-H. Liu, W.-J. Liu, X.-Y. Yu, X.-L. Qi, C.-C. Sunu, published in Eur Rev Med Pharmacol Sci 2020; 24 (20): 10375-10382-DOI: 10.26355/eurrev_202010_23387-PMID: 33155193" has been retracted by the authors due to inaccuracies related to the misuse of Table I. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23387.

[Research advances on mesenchymal stem cell-derived extracellular vesicles in promoting angiogenesis of diabetic ulcers].

Extracellular vesicles are nanoparticles secreted by most eukaryotic cells and play important roles in material transport and information transmission between cells, involved in inflammation, angiogenesis, antigen presentation, cell apoptosis, cell differentiation, and other biological processes. The culture supernatant of mesenchymal stem cells is rich in extracellular vesicles, and the extracellular vesicles can regulate the formation of new blood vessels, a key step in wound healing and tissue repair. The persistence of diabetic ulcers is closely related to the blocked formation of wound vascular network. This article reviews the role of extracellular vesicles derived from mesenchymal stem cells in promoting angiogenesis of diabetic ulcers, in order to provide a new idea for the treatment of diabetic ulcers.

[Establishment of morphological reference values for the differential count of white blood cells in peripheral blood smear, as well as nucleated cells and megakaryocytes in bone marrow smear].

Objective: To establish the morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear. Methods: From April 2012 to June 2020, 4 221 healthy donors for hematopoietic stem cell transplantation in Hebei Yanda Lu Daopei Hospital were selected. The median age was 36 (3-72) years old, including 2 520 males and 1 701 females. They were divided into four groups according to age: children group, with age≤14 years old [n=334, 11 (3-14) years old], youth group, with age >14 years old and <45 years old [n=2 855, 33 (15-44) years old], middle-aged adult group, with age ≥45 years old and < 60 years old [n=929, 49 (45-59) years old], and older adult group, with age ≥60 years old [n=103, 62 (60-72) years old]. Gender subgroups were established in each age group. According to different hematopoietic characteristics, the children group were divided into two subgroups: children group 1 [n=48, 6 (3-7) years old] and children group 2 [n=286, 11 (8-14) years old]. According to the clinical routine, 100 white blood cells in peripheral blood, 200 nucleated cells in bone marrow, and cell numbers/4.5 cm2 for megakaryocytes were classified and counted. The results of cell count in different age and gender groups were compared, and the reference values of morphological classification were established for different groups with statistical or clinical significance. Results: Due to the existence of statistically significant differences between children and adult groups and different gender subgroups in adults (all P<0.05), the reference values were established for children group and adult gender subgroups. The counts of segmented neutrophils and lymphocytes in peripheral blood were 46.65(43.97-49.32)% and 44.00(10.60-65.10)% in children group 1, 50.73(49.50-51.96)% and 39.55 (38.36-40.74)% in children group 2, and 57.00 (39.00-75.23) % and 33.00 (17.00-52.00) % in adult group, respectively. Bone marrow segmented neutrophils, orthochromatic erythroblasts, and mature lymphocytes were 11.54 (10.68-12.41)%, 14.20 (13.19-15.21)%, and 23.99 (22.06-25.92)% in children group 1, 12.50 (7.00-21.50)%, 15.00(9.50-25.50)%, and 21.02 (20.24-21.81)% in children group 2, 13.50 (7.50-21.00)%, 16.50 (10.50-26.00)%, and 15.50 (7.50-26.00)% in adult male group, and 14.50 (8.00-24.50)%, 14.50 (9.00-23.00)%, and 17.50 (8.50-29.00)% in adult female group, respectively. The myelopoiesis/erythropoiesis ratio in children group, adult male group and adult female group was 1.86∶1 (1.14∶1-3.23∶1), 1.96∶1 (1.12∶1-3.19∶1), 2.22∶1 (1.30∶1-3.69∶1), respectively. The numbers of granular megakaryocytes and thromocytogenic megakaryocytes were 138 (25-567) cells/4.5cm2 and 86 (13-328) cells/4.5 cm2 in children group, and 92 (13-338) cells/4.5 cm2 and 38 (3-162) cells/4.5 cm2 in adult group, respectively. Conclusion: The morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear are successfully established, which is helpful to improve the application of morphological examination in disease screening, diagnosis and monitoring.

[Application of electric tube stapler in laparoscopic colorectal tumor surgery].

Objective: To investigate the application of electric tube stapler in laparoscopic colorectal tumor surgery. Methods: A descriptive case series study was conducted. Clinical data of patients who underwent laparoscopic colorectal surgery in Peking Union Medical College Hospital in August 2021 using domestic electric tube stapler were collected to analyze the occurrence of postoperative anastomotic leakage, anastomotic bleeding and other complications as well as postoperative intestinal function recovery. Results: A total of 11 patients with colorectal tumor were enrolled in this study, including 8 males and 3 females. Eight patients underwent laparoscopic low anterior resection (1 patient underwent protective ileostomy), and three patients underwent laparoscopic sigmoid carcinoma radical resection. During operation, power system failure of stapler occurred in 1 patient, and the replacement manual device was used to complete the anastomosis. No anastomotic leakage or bleeding occurred in the cohort of patients. There was no conversion to laparotomy or conventional anastomosis. One patient developed acute myocardial infarction 2 days after surgery. The average time to the first flatus after surgery was (2.4±0.8) days and the average length of hospital stay was (10.0±6.1) days. Conclusions: The application of electric tube stapler in laparoscopic colorectal tumor surgery has many advantages, such as safe and effective anastomosis, low morbidity of postoperative complications, and rapid recovery of intestinal function. Domestic electric tube stapler can be applied in minimally invasive surgery for colorectal tumor.

Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p.

The article "Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p, by Y. Mu, W.-J. Liu, L.-Y. Bie, X.-Q. Mu, Y.-Q. Zhao, published in Eur Rev Med Pharmacol Sci 2021; 25 (1): 145-153-DOI: 10.26355/eurrev_202101_24378-PMID: 33506902" has been withdrawn from the authors since the design of the manuscript was not rigorous enough (there were some flaws in some experiments). The authors explain that they will perform further experiments. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/24378.

Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p.

OBJECTIVE: The incidence of pulmonary adenocarcinoma locates first in all the malignant tumors in the world. At present, there are many diagnostic methods for pulmonary adenocarcinoma, but there are a few methods that are mature or have ideal application prospects. We aim to explore the role of VRK2 in the occurrence and development of pulmonary adenocarcinoma and its possible regulatory mechanism. PATIENTS AND METHODS: Western blot and qRT-PCR were performed to assess the expression of VRK2. Flow cytometry, Western blot, and Caspase-3 colorimetric assay Kit were used to evaluate the apoptosis level. The proliferation, migration, and invasion ability were measured via cell cycle assay, wound healing, and transwell invasion assay. Luciferase assay verified the relationship between VRK2 and miR-145-5p. The effect of FGD5-AS1 on tumorigenesis of glioma was detected by the xenograft nude mice model. RESULTS: VRK2 was significantly increased in tumor tissues and cell lines. Loss of VRK2 promoted apoptosis level and inhibited the proliferation, migration, and invasion in A549 cells via regulating the ERK1/2/AKT signal pathway. Luciferase assay reported that VRK2 could bind with miR-145-5p. The level of miR-145-5p was negatively correlated with the expression of VRK2 and involved in VRK2 regulating tumor progression. The tumor growth assay showed that the silencing of VRK2 inhibited tumorigenesis with the inactivating ERK1/2/AKT pathway. CONCLUSIONS: Knockdown of VRK2 inhibited the development of pulmonary adenocarcinoma via regulating the ERK1/2/AKT signal pathway by targeting miR-145-5p, which providing some novel experimental basis for clinical treatment of pulmonary adenocarcinoma.

[Clinical features and prognosis of low triiodothyronine syndrome in patients with acute myeloid leukemia].

Objective: To investigate the clinical features and prognosis of low triiodothyronine syndrome (LT3S) in patients with acute myeloid leukemia (AML) . Methods: A total of two 236 patients with AML who presented at the Jiangsu Provincial Hospital between January 2013 and December 2019 were included, and their data were retrospectively reviewed. The patients were divided into two groups, including the LT3S group and the non-LT3S group, according to their serum thyroxine level. The clinical characteristics and prognosis of the two groups were compared. Results: Among the 236 patients, 62 (26.3%) patients had LT3S. Serum-free T3 level was positively correlated with albumin (r=0.443, P<0.001) and hemoglobin (r=0.187, P=0.005) levels and negatively correlated with C-reactive protein (r=-0.406, P<0.001) and lactate dehydrogenase (r=-0.274, P<0.001) levels. The overall survival (OS) (7.5 months vs 29.9 months, P<0.001) and progression-free survival (PFS) (2.0 months vs 24.0 months, P<0.001) were significantly shortened in the LT3S group compared with the non-LT3S group. After propensity score matching, the OS (9.6 months vs 30.4 months, P=0.010) and PFS (3.0 months vs 30.0 months, P=0.014) were still significantly reduced in the LT3S group compared with the non-LT3S group. Therefore, LT3S was an independent risk factor for OS (HR=2.553, 95% CI 1.666-3.912, P<0.001) and PFS (HR=1.701, 95% CI 1.114-2.597, P=0.014) in patients with AML. Subgroup analysis suggested that patients with LT3S had a worse prognosis in patients with AML who were obese, fragile, or treated with standard chemotherapy. Conclusions: The occurrence of LT3S reflects the poor clinical status and prognosis of patients with AML.

Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9.

OBJECTIVE: Our purpose was to assess the relationship between circ_0005276 and clinical features of epithelial ovarian cancer (EOC), and to illustrate the regulatory effect of circ_0005276 on migratory potential in EOC cells. PATIENTS AND METHODS: EOC tissues and adjacent normal ones were collected from 49 EOC patients. Relative levels of circ_0005276 and ADAM9 in EOC tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ_0005276 and clinical features of EOC patients was analyzed. Moreover, migratory potentials of CAOV3 and SKOV3 cells affected by circ_0005276 were examined by transwell and wound healing assay. Regulatory effects of circ_0005276/ADAM9 feedback loop on the development of EOC were finally detected by Luciferase assay and rescue experiments. RESULTS: It was found that circ_0005276 was upregulated in EOC tissues and its level was positively linked to rates of lymphatic metastasis and distant metastasis in EOC patients. Survival analysis showed worse OS and DFS in EOC patients expressing a high level of circ_0005276 than those with a low level. Besides, knockdown of circ_0005276 attenuated migratory potentials in EOC cells. ADAM9 was verified to be the target gene binding circ_0005276, and its level was positively regulated by circ_0005276. Notably, circ_0005276 aggravated the development of EOC by targeting ADAM9. CONCLUSIONS: Circ_0005276 is highly expressed in EOC tissues, and its level is positively linked to metastasis. Serving as an unfavorable gene in the prognosis of EOC, circ_0005276 aggravates the development of EOC by upregulating ADAM9.

Role of visfatin in promoting proliferation and invasion of colorectal cancer cells by downregulating SDF-1/CXCR4-mediated miR-140-3p expression.

OBJECTIVE: Visfatin is significantly upregulated in colorectal cancer (CRC). However, its exact role in CRC progression and the regulatory mechanism involved in this process have not been fully illuminated. The aim of this study was to investigate the roles of visfatin in CRC progression and the potential molecular mechanism. MATERIALS AND METHODS: In vitro, two CRC cell lines (DLD-1 and SW480) were transfected with visfatin, si-visfatin, and their control vectors. Some cells were transfected with miR-140-3p mimics or miRNA negative control. Cell Counting Kit-8 and transwell invasive assays were used to detect cell proliferation and invasion ability. Luciferase reporter assays were performed to confirm whether CXC motif chemokine receptor 4 (CXCR4) directly targets miR-140-3p. Western blotting and qRT-PCR analyses were respectively conducted to evaluate the protein and mRNA levels of stromal cell-derived factor-1 (SDF-1) and CXCR4. In vivo, DLD-1 cells transfected with visfatin construct or vector control were inoculated into nude mice. After 5 weeks, the mice were sacrificed, and the tumor nodules were weighed. The expression of visfatin, SDF-1, and CXCR4 in tumor tissues was detected via immunohistochemistry analysis. RESULTS: In vitro, the transfection of visfatin promoted the proliferation and invasion of CRC cells, as well as upregulated the expression of SDF-1/CXCR4. MiR-140-3p directly targets the 3'untranslated region of CXCR4. MiR-140-3p expression was downregulated by treatment with visfatin, and miR-140-3p exerted similar effects to those of visfatin knockdown on the proliferation and invasion of CRC cells. In vivo, visfatin stimulated CRC tumor growth and downregulated miR-140-3p expression, whereas it upregulated SDF-1/CXCR4 expression. CONCLUSIONS: Visfatin promotes CRC progression by downregulating the SDF-1/CXCR4-mediated expression of miR-140-3p both in vitro and in vivo.

Osteopontin accelerates chondrocyte proliferation in osteoarthritis rats through the NF-κb signaling pathway.

OBJECTIVE: To explore the influence of osteopontin (OPN) on the chondrocyte proliferation in osteoarthritis (OA) rats. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were divided in the control group (n=10), model group (n=10), and OPN knockdown group (n=10). No treatment was performed in the control group, while OA rats were administrated with control adenovirus in the model group and OPN knockdown adenovirus in the OPN knockdown group. After sampling, the degree of OA was evaluated via hematoxylin-eosin (HE) staining, and the mRNA expression of OPN was detected. Moreover, the expression of the proliferation-associated protein cyclin D1 was detected using immunohistochemistry. The chondrocytes were isolated from the normal rats, cultured, and transfected with OPN overexpression vector or si-OPN. Methyl thiazolyl tetrazolium (MTT) assay was adopted to determine the proliferative capacity of chondrocytes, and Caspase3 activity was measured to evaluate the changes in the apoptotic capacity of chondrocytes. Meanwhile, Western blotting was performed to verify the influences of OPN on the pathways on chondrocyte proliferation. RESULTS: After the OA model was established, the expression level of OPN significantly increased. According to HE staining results, OPN knockdown effectively inhibited the onset of OA. Compared with that in the control group, the expression level of cyclin D1 in the model group was raised. However, upregulated cyclin D1 in OA rats was repressed in OPN knockdown group. OPN overexpression promoted the proliferation of chondrocytes, but suppressed their apoptosis, while OPN knockdown had the opposite effects. Besides, OPN overexpression upregulated nuclear factor-κB (NF-κB), and NF-κB knockdown eliminated the regulatory effects of OPN on proliferation and apoptosis of chondrocytes. CONCLUSIONS: OPN promotes the expression of NF-κB signals to accelerate chondrocyte proliferation, thereby inducing OA in rats.

[Risk factor analysis on anastomotic leakage after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and establishment of a nomogram prediction model].

Objective: To investigate the risk factors of anastomotic leakage (AL) after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and construct a nomogram prediction model. Methods: This study was a retrospective case-control study that collected and reviewed the clinicopathological data of 359 patients who underwent laparoscopic surgery from January 2012 to January 2018, including 202 patients from the Department of General Surgery, Nanfang Hospital of Southern Medical University and 157 patients from the Department of Gastrointestinal Surgery of Fujian Provincial Cancer Hospital. Inclusion criteria: (1) age ≥ 18 years old; (2) diagnosis as rectal cancer by biopsy before treatment; (3) distance from tumor to anus within 12 cm; (4) locally advanced stage (T3-T4 or N+) diagnosed by imaging (CT, MRI, PET or ultrasound); (5) standardized neoadjuvant therapy followed by laparoscopic radical operation. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) short-term or incomplete standardized neoadjuvant therapy; (3) Miles, Hartmann, emergency surgery, palliative resection; (4) conversion to open surgery. Clinicopathological data, including age, gender, body mass index (BMI), preoperative albumin, distance from tumor to anus, operation hospital, American Society of Anesthesiologists score (ASA score), operation time, T stage, N stage, M stage, TNM stage, pathological complete response (pCR) were analyzed with univariate analysis to identify predictors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. Then, incorporated predictors of AL, which were screened by multivariate logistic regression, were plotted by the "rms" package in R software to establish a nomogram model. According to the scale of the nomogram of each risk factor, the total score could be obtained by adding each single score, then the corresponding probability of postoperative AL could be acquired. The area under ROC curve (AUC) was used to evaluate the predictive ability of each risk factor and nomogram on model. AUC > 0.75 indicated that the model had good predictive ability. The Bootstrap method (1000 bootstrapping resamples) was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index) whose rage was 0.5 to 1.0. Higher C-index indicated better consistency with actual risk. The calibration curve was used to assess the calibration of prediction model. The Hosmer-Lemeshow test yielding a non-significant statistic (P>0.05) suggested no departure from the perfect fit. Results: Of 359 cases, 224 were male, 135 were female, 189 were ≥ 55 years old, 98 had a BMI > 24 kg/m(2), 176 had preoperative albumin ≤ 40 g/L, 128 had distance from tumor to anus ≤ 5 cm, 257 were TNM 0-II stage, 102 were TNM III-IV stage, and 84 achieved pCR after neoadjuvant therapy. The incidence of postoperative AL was 9.5% (34/359). Univariate analysis showed that gender, preoperative albumin and distance from tumor to the anus were associated with postoperative AL (All P<0.05). Multivariate logistic regression analysis revealed that male (OR=2.480, 95% CI: 1.012-6.077, P=0.047), preoperative albumin ≤40 g/L (OR=5.319, 95% CI: 2.106-13.433, P<0.001) and distance from tumor to anus ≤ 5 cm (OR=4.339, 95% CI: 1.990-9.458, P<0.001) were significant independent risk factors for postoperative AL. According to these results, a nomogram prediction model was constructed. The male was for 55 points, the preoperative albumin ≤ 40 g/L was for 100 points, and the distance from tumor to the anus ≤ 5 cm was for 88 points. Adding all the points of each risk factor, the corresponding probability of total score would indicated the morbidity of postoperative AL predicted by this nomogram modal. The AUC of the nomogram was 0.792 (95% CI: 0.729-0.856), and the C-index was 0.792 after internal verification. The calibration curve showed that the predictive results were well correlated with the actual results (P=0.562). Conclusions: Male, preoperative albumin ≤ 40 g/L and distance from tumor to the anus ≤ 5 cm are independent risk factors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. The nomogram prediction model is helpful to predict the probability of AL after surgery.

Mechanism of resistance and therapeutic prospect of leukemia mediated by signaling pathway in bone marrow microenvironment.

Leukemia is a malignant disease of the blood system. Although the current research on the pathogenesis of leukemia is more and more in-depth and has an influential guiding significance for the ongoing clinical treatment of leukemia, its resistance and recurrence is still a challenging problem that needs to be solved. At present, several studies have indicated that the bone marrow microenvironment played an essential role in drug resistance of leukemia, forming a protective spot for them by interacting with leukemic cells, offering protective effects of leukemia cells from cytotoxic drugs. The bone marrow microenvironment can mediate the development of drug resistance in leukemia through many signal pathways, by affecting the growth, propagation, and apoptosis of leukemia cells. The microenvironment can promote cell survival, proliferation, and anti-apoptosis, and then mediate the drug resistance of leukemia. It is considered as a better guidance of clinical treatment by understanding the drug resistance mechanism of leukemia.

Low plasma miR-25 expression is a favorite prognosis factor in non-small cell lung cancer.

OBJECTIVE: Circulating microRNAs (miRNAs) are promising biomarkers for the diagnosis and prognosis prediction of cancer. In the study, we aimed to investigate the potential clinical significance of the plasma miR-25 in non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We first compared the miRNAs expression pattern between NSCLC tissues and adjacent normal tissues then, bioinformatic analysis of the downstream targets of miR-25 was performed. The diagnostic and prognostic value of the plasma miR-25 in NSCLC was then evaluated. RESULTS: The expression level of miR-25 was increased in NSCLC tissues compared to the adjacent normal tissues. In addition, bioinformatic analysis of the downstream-targeted genes of miR-25 revealed that many gene ontology functions and pathways were associated with cancer progression. The levels of plasma miR-25 were significantly upregulated in NSCLC patients compared to normal controls. In addition, the plasma miR-25 levels were especially higher in NSCLC patients with positive lymph node metastasis, poorly differentiation or advanced clinical stage. Subsequently, we found that the plasma miR-25 expression levels were dramatically decreased in 45 NSCLC patients after receiving surgical treatment. The receiver operating characteristic (ROC) curve analysis indicated that the plasma miR-25 exhibited high diagnostic sensitivity and specificity to discriminate NSCLC cases from healthy subjects. More interestingly, the combination of the plasma miR-25 and carcinoembryonic antigen (CEA) could effectively enhance the accuracy for distinguishing NSCLC patients from normal controls. Moreover, the plasma miR-25 overexpression was closely correlated with aggressive clinical characteristics and poor survival. Finally, the plasma miR-25 was identified as an independent prognostic marker for the overall survival of NSCLC. CONCLUSIONS: Collectively, our findings demonstrated that the plasma miR-25 might serve as a novel promising biomarker in the diagnosis and prognosis prediction of NSCLC.