The Clinical Significance of Subtle Distal Fallopian Tube Abnormalities: A Multicentre Prospective Observational Study.

Background: Subtle distal fallopian tube abnormalities are a group of diseases characterised by small variations in tubal anatomy. The clinical significance of these abnormalities need to be studied. Objectives: The purpose of this multicentre prospective observational study was to investigate whether subtle distal fallopian tube abnormalities are related to infertility and endometriosis. Materials and Methods: The investigation was carried out in five medical centres in China and France from February to July 2021 and included reproductive-age patients who underwent gynaecological laparoscopy. Subtle abnormalities included Hydatid of Morgagni (HM) , fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis, and accessory fallopian tube. Results: 642 patients were enrolled in the study and 257 (40.0%) were diagnosed with subtle tube abnormalities. Hydatid of Morgagni was the most common abnormality (22.7%; n=146), followed by fimbrial agglutination (19.8%; n=127), tubal diverticula (6.9%; n=44), accessory tube (2.0%; n=13), and tubal accessory ostium (1.9%; n=12). Fimbrial phimosis was the least common abnormality (0.3%; n=2). The prevalence of subtle fallopian tube abnormalities was significantly higher among infertile patients (188/375, 50.1%) than those without history of infertility (69/267, 25.8%, ᶍ2=38.332, P=0.000). 209 patients were diagnosed with endometriosis during surgery, and the prevalence of subtle abnormalities was significantly higher in the endometriosis group than in those without endometriosis (61.2%, [128/209] vs. 29.8% [129/433], ᶍ2=58.086, P=0.000). Conclusions: Higher prevalence of subtle tubal abnormalities suggests that they may contribute to infertility. They are highly related to endometriosis and indicate fimbrial abnormalities of endometriosis. What is new?: This is the largest multicentre study to investigate the subtle distal fallopian tube abnormalities in infertile women. Compared to previous studies, this study includes the main subtle distal abnormalities and the control group patients without a history of infertility.

[Management strategy of femoral artery pseudoaneurysm combined with infectious wounds].

Objective: To investigate the surgical treatment methods of femoral artery pseudoaneurysm combined with infectious wounds and to evaluate the clinical effects. Methods: The retrospective observational research method was used. Twelve patients with femoral artery pseudoaneurysm combined with infectious wounds who met the inclusion criteria were admitted to Nanjing University of Chinese Medicine Wuxi Integrated Traditional Chinese and Western Medicine Hospital (Affiliated Hospital of Jiangnan University) from October 2014 to September 2022, including 6 males and 6 females, aged from 46 to 78 years. In the primary operation, debridement, tumor resection, and artery suture/venous grafting to repair the artery/artery ligation were performed, and the wound area after tumor resection ranged from 4.0 cm×1.5 cm to 12.0 cm×6.5 cm. Wounds that could be sutured were treated with tension reduction suture and extracutaneous continuous vacuum sealing drainage (VSD), while large wounds that could not be sutured were treated with VSD to control infection. In the secondary operation, tension reduction suture was performed to repair the wounds that could be sutured; large wounds were repaired with adjacent translocated flaps with area of 9.0 cm×5.0 cm to 15.0 cm×7.0 cm. Additionally, when the length of the exposed femoral artery was equal to or over 3.0 cm, the wounds were repaired with additional rectus femoris muscle flap with length of 15.0 to 18.0 cm. The donor areas of the flaps were directly sutured. The wound with artery ligation was treated with stamp skin grafting and continuous VSD. The bacterial culture results of the wound exudate samples on admission were recorded. The intraoperative blood loss, the location of femoral artery rupture, the artery treatment method, and the wound repair method in the primary operation were recorded, and the durations of catheter lavage, catheter drainage, and VSD treatment, and the drainage volume after the operation were recorded. The repair method of wounds in the secondary operation, the durations of catheter drainage and VSD treatment, and the total drainage volume after the operation were recorded. The survivals of flap/muscle flap/stamp skin grafts were observed, and the wound healing time was recorded. Follow-up after discharge was performed to evaluate the quality of wound healing and the walking function and to check whether the pulsatile mass disappeared. B-ultrasound or computed tomography angiography (CTA) was performed again to observe potential pseudoaneurysm recurrence and evaluate the patency of blood flow of the femoral artery. Results: The bacterial culture results of wound exudate samples of all the patients were positive on admission. The blood loss was 150 to 750 mL in the primary operation. The arterial ruptures were located in the femoral artery in 8 cases, in the external iliac artery in 2 cases, and in the femoral arteriovenous fistula in 2 cases. Six cases received direct artery suture, 4 cases received autologous great saphenous vein grafting to repair the artery, 1 case received autologous great saphenous vein bypass surgery, and 1 case received artery ligation. The primary wound suture was performed in 4 cases, along with catheter lavage for 3 to 5 days, catheter drainage for 4 to 6 days, VSD treatment for 5 to 7 days, and a total drainage volume of 80 to 450 mL after the surgery. In the secondary operation, the wounds were sutured directly in 3 cases along with catheter drainage for 2 to 3 days, the wound was repaired with scalp stamp skin graft and VSD treatment for 5 days in 1 case, the wounds were repaired with adjacent translocated flaps in 2 cases with catheter drainage for 2 to 3 days, and the wounds were repaired with rectus femoris muscle flaps+adjacent translocated flaps in 2 cases with catheter drainage for 3 to 5 days . The total drainage volume after the secondary operation ranged from 150 to 400 mL. All the skin flaps/muscle flaps/skin grafts survived after operation. The wound healing time ranged from 15 to 36 days after the primary operation. Follow-up of 2 to 8 months after discharge showed that the wounds of all patients healed well. One patient who underwent femoral artery ligation had calf amputation due to foot ischemic necrosis, and the rest of the patients regained normal walking ability. The pulsatile mass disappeared in inguinal region of all patients. B-ultrasound or CTA re-examination in 6 patients showed that the blood flow of femoral artery had good patency, and there was no pseudoaneurysm recurrence. Conclusions: Early debridement, tumor resection, and individualized artery treatment should be performed in patients with femoral artery pseudoaneurysm combined with infected wounds. Besides, proper drainage and personalized repair strategy should be conducted according to the wound condition to achieve a good outcome.

Application of B-flow imaging and its enhanced mode in perforator mapping.

AIM: To explore the value of B-flow (B-mode blood flow) imaging and its enhanced mode in perforator mapping. MATERIALS AND METHODS: Before surgery, B-flow imaging, enhanced B-flow imaging, colour Doppler flow imaging (CDFI), and contrast-enhanced ultrasound (CEUS) were used to detect the skin-perforating vessels and small vessels in the fat layer of the donor site. Taking the intra-operative results as the reference standard, the diagnostic consistency and efficiency of the four modes were compared. Statistical analysis was performed using the Friedman M-test, Cochran's Q-test, and the Z-test. RESULTS: Thirty flaps were excised, with 34 skin-perforating vessels and 25 non-skin-perforating vessels, as confirmed during surgery. In order of the number of skin-perforating vessels detected, the results showed that enhanced B-flow imaging detected more vessels than B-flow imaging and CDFI (all p<0.05), CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05), B-flow imaging detected more vessels than CDFI (p<0.05). All four modes had remarkable and satisfactory diagnostic consistency and effectiveness, but B-flow imaging was the best (sensitivity 100%, specificity 92%, Youden index 0.92). In order of the number of small vessels in the fat layer detected, the results showed that enhanced B-flow imaging detected more vessels than CEUS, B-flow imaging, and CDFI (all p<0.05). CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05). CONCLUSION: B-flow imaging is an alternative method for perforator mapping. Enhanced B-flow imaging can reveal the microcirculation of flaps.

[Application and prospect of tissue engineering strategies based on decellularized extracellular matrix in bone-tendon injuries].

Under the rapid development of national health and fitness, the incidence rates of bone-tendon injuries have been increasing observably. Bone-to-tendon healing poses a formidable clinical challenge due to the complex structure, composition and mechanics of the interface. A variety of strategies, including advanced biomaterials, bioactive growth factors and multiple stem cell lineages, have been developed, providing new adjuvant therapies for the repair of motor system injuries. Among them, tissue engineering of decellularized extracellular matrix materials is one of the most promising approaches. The well-designed shapes of scaffolds, the improvements of acellular protocols, the bioactivity enhancement of materials and the appropriate seed cells in biomimetic applications have been proved to have more satisfactory clinical efficacy and application prospects. This review intends to provide a reference for future innovations in bone-tendon injury by summarizing the research progresses of tissue engineering strategies in recent years.

[Effects of porcine urinary bladder matrix on motility and polarization of bone marrow-derived macrophages in mice].

Objective: To explore the effects of porcine urinary bladder matrix (UBM) on the motility and polarization of bone marrow-derived macrophages in mice, so as to provide evidence for the rational selection of stent in clinical wound repair. Methods: The method of experimental research was used. The microstructure of porcine UBM and absorbable dressing was observed under scanning electron microscope. Polyacrylamide gel electrophoresis was used to observe the protein distribution of the two stent extracts. The primary macrophages were induced from bone marrow-derived cells isolated from six 6-8-week-old male C57BL/6J mice (mouse age, sex, and strain, the same below) and identified. Three batches of macrophages were divided into porcine UBM extract group and absorbable dressing extract group. The cells in each group were cultured with Dulbecco's modified Eagle medium/F12 medium containing the corresponding extracts. The cell migration rate was detected and calculated on 1, 3, and 7 d after scratching by scratch test. The number of migrated cells at 12 and 24 h of culture was detected by Transwell experiment. The percentages of CD206 and CD86 positive cells at 24 h of culture was detected by flow cytometer. The numbers of sample in the above cell experiments were all 3. An incision was prepared on the left and right back of twelve mice, respectively. The left incision of each mouse was included in porcine UBM group and the right incision was included in absorbable dressing group, and the corresponding stents were implanted into the incisions respectively. On post operation day (POD) 7 and 14, the number of inflammatory cells infiltrated in the stent was detected by hematoxylin-eosin staining; the number of F4/80, transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), and matrix metalloprotein-9 (MMP-9) positive cells and type Ⅰ collagen deposition in stents were observed by immunohistochemistry; the percentages of F4/80, CD86, and CD206 positive cells were observed by immunofluorescence staining. The numbers of sample in the above animal experiments were all 6. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, and independent sample t test. Results: Porcine UBM has a dense basement membrane structure on one side and porous propria containing a fibrous structures on the other. Both sides of the absorbable dressing had three-dimensional porous structure. In the molecular weight range of (50-70)×103, multiple non-type Ⅰ collagen bands appeared in the lanes of porcine UBM extract, while no obvious bands appeared in the lanes of absorbable dressing extract. It had been identified that mouse bone marrow-derived cells had been successfully induced into macrophages. The cell migration rates in porcine UBM extract group were significantly higher than those in absorbable dressing extract group on 1, 3, and 7 d after scratching (with t values of 15.31, 19.76, and 20.58, respectively, P<0.05). The numbers of migrated cells in porcine UBM extract group were significantly more than those in absorbable dressing extract group at 12 and 24 h of culture (with t values of 12.20 and 33.26, respectively, P<0.05). At 24 h of culture, the percentage of CD86 positive cells in porcine UBM extract group ((1.27±0.19)%) was significantly lower than (7.34±0.14)% in absorbable dressing extract group (t=17.03, P<0.05);the percentage of CD206 positive cells in porcine UBM extract group was (73.4±0.7)%, significantly higher than (32.2±0.5)% in absorbable dressing extract group (t=119.10, P<0.05). On POD 7 and 14, the numbers of inflammatory cells infiltrated in the stents in porcine UBM group was significantly more than those in absorbable dressing group (with t values of 6.58 and 10.70, respectively, P<0.05). On POD 7 and 14, the numbers of F4/80, TGF-ß1, VEGF, and MMP-9 positive cells in the stents in porcine UBM group were significantly more than those in absorbable dressing group (with t values of 46.11, 40.69, 13.90, 14.15, 19.79, 32.93, 12.16, and 13.21, respectively, P<0.05); type Ⅰ collagen deposition in the stents in porcine UBM group was more pronounced than that in absorbable dressing group; the percentages of CD206 positive cells in the stents in porcine UBM group were significantly higher than those in absorbable dressing group (with t values of 5.05 and 4.13, respectively, P<0.05), while the percentages of CD86 positive cells were significantly lower than those in absorbable dressing group (with t values of 20.90 and 19.64, respectively, P<0.05), and more M2-type macrophages were seen in the stents in porcine UBM group and more M1-type macrophages were seen in the stents in absorbable dressing group. Conclusions: Porcine UBM can enhance macrophage motility, induce M2 polarization and paracrine function, create a microenvironment containing growth factors such as TGF-ß1 and MMP-9 tissue remodeling molecules, and promote tissue regeneration and extracellular matrix remodeling in mice.

[The prevalence and risk factors of diabetic peripheral artery disease in Chinese communities].

Objective: To investigate the prevalence and risk factors of diabetic peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) managed in primary health care in China. Methods: A total of 2 528 T2DM patients were selected using a two-stage cluster random sampling method based on the baseline survey of the "China Diabetic Foot Prevention Model Project." The study was conducted in 2015 among T2DM patients in 8 primary healthcare centers in Changshu county and Jiang'an district of Wuhan, China. Data collection methods included a questionnaire, body measurement, and blood glucose detection. The Ankle-Brachial Index (ABI) is the most widely used noninvasive vascular test. A binary logistic regression model was used to analyze the influence factors. Results: The prevalence of PAD was 11.2% among the diabetic patients managed in primary health care in the two cities. The prevalence of PAD under 55 years old, 55- years old, 65- years old, and ≥75 years old were 7.8%, 6.0%, 12.9% and 22.5%, respectively. Multivariate stepwise logistic regression identified influence factors included older age, higher education level, smoking, drinking, postprandial glucose uncontrol, and prior myocardial infarction or angina. Compared to age <55 years, the odds ratio for PAD were 0.74 for 55- years (95%CI: 0.43-1.28), 1.72 for 65- years (95%CI: 1.05-2.81), 3.56 for 75 years and above (95%CI: 2.07-6.11), respectively. Compared to patients with education in primary school and below, the odds ratio was 1.37 (95%CI: 0.97-1.94), 2.48 (95%CI: 1.73-3.55), 1.99 (95%CI: 1.26-3.13) for those with education levels of junior high school, senior high school, and college, respectively. Current smoking (OR=1.49, 95%CI: 1.02-2.17), current drinking (OR=0.45, 95%CI: 0.28-0.71), postprandial glucose uncontrol (2 h postprandial plasma glucose >10.0 mmol/L: OR=1.72, 95%CI: 1.22-2.43), and prior myocardial infarction or angina (OR=2.32, 95%CI: 1.50-3.61) were influencing factors of PAD. Conclusions: Despite the high prevalence of PAD in diabetes managed in primary health care; multiple risk factors are not effectively aware of and under control. It is urgent to promote ABI screening and standardized management for diabetes, especially in primary health care.

[Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria].

Objective: To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored. Methods: The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children's Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively. Results: There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions: The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

[Establishment and analysis of prediction model for invasive subsolid pulmonary nodules based on radiomics].

Objective: To evaluate the best radiomic features based prediction model for identifying the histopathological subtypes of invasive adenocarcinoma or noninvasive pulmonary nodules appearing as subsolid nodules. Methods: A total of 352 patients (108 males and 244 females, median age was [M(Q1,Q3)]57 (50,65), underwent high-resolution chest CT and appearing as subsolid nodules and further treated by surgical resection whose subsequently pathological results were classified as atypical adenomatous hyperplasia (AAH), carcinoma in situ (AIS), microinvasive carcinoma (MIA), invasive adenocarcinoma (IA), from January 2015 to September 2019, in Radiology Department of Zhongda Hospital Affiliated to Southeast University and Jinling Hospital, Medical School of Nanjing University were retrospectively collected. They were divided into non-invasive group (n=233) and invasive group (n=119) according to pathological findings. According to the ratio of training set: internal test set: external test set, which is about 3∶1∶1,the patients in Zhongda Hospital Affiliated to Southeast University were randomly divided into training set (n=215, non-IA∶IA 155∶60) and internal test set(n=69, non-IA∶IA 52∶17), meanwhile a certain number of patients in Jinling Hospital, Medical School of Nanjing University(n=68, non-IA∶IA 26∶42)were randomly selected as an independent external test set. Particular quantitative parameters of the nodules, radiomic features, morphological characteristics, clinical data, and serum tumor markers were recorded. Radiomic label was constructed using LASSO regression method. The morphological model, CT model and comprehensive model were constructed by binary logistic regression and were verified in test sets, respectively. Results: Shape_MinorAxis(Gradient),Glszm_ZoneEntropy(LBP) were selected as the two most significant features based on training set. Radiomic tag=1.065 75×Shape_MinorAxis(Gradient)+0.030 58×Glszm_ZoneEntropy(LBP). Comparing the prediction performance of all models in each data cohort, the CT model (Ln(P/1-P)=-2.417 11+1.031 60×Radimic tag+1.203 06×Diameter+1.614 21×(Pleural indentation sign = Y) constructed by radiomic label, pleural depression, and quantitative parameters (diameter, average density) was much better than other models and was chosen as the optimal model, with an AUC of CT models in training cohort and test cohort was 0.954 (95%CI: 0.927-0.981), 0.865 (95%CI:0.764-0.966), better than morphological model 0.857 (95%CI:0.796-0.918), 0.818(95%CI: 0.686-0.949) and comprehensive model 0.951(95%CI: 0.921-0.981), 0.856(95%CI: 0.730-0.982), respectively. Conclusion: The integrative CT model has a better prediction efficiency for identifying invasive or noninvasive nodules appearing as subsolid nodules.

[New bioactive materials for promoting wound repair and skin regeneration].

The modulation of microenvironment is a key technology towards promoting wound repair and skin regeneration. In recent years, a series of new bioactive materials that modulate the microenvironment and cell behaviors have been developed, demonstrating highly efficient capability of inducing wound repair and skin appendage regeneration. This article summarizes the research development of related new bioactive materials and their mechanisms of action.

[Application of cloud-based information platform in China National Birth Cohort].

Birth cohort is an important observational study which can continuously and dynamically collect the exposure changes and health outcomes from gametophyte development to adolescence and even old age. However, because of its complex design and difficult implementation, how to construct birth cohort with high quality and high efficiency is the main difficulty faced by epidemiologists at home and abroad. In 2016, China National Birth Cohort was officially launched. The network and information technology were used to explore, and a set of "cloud-based information platform" was established to support this queue construction, containing 16 units in China. After four years of development, the platform has formed a complete set of programs about the construction of cohort information platform, which including recruitment and follow-up management of participants, real-time data interaction, queue quality control, multi-level authority management and function division. The relevant design framework and functional elements provide the references to the future information construction of large-scale birth cohort and even population-based research in China.

[The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort].

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

[Metabolism and transport pathway of prostaglandin E2 and its role in liver regeneration].

The liver is an organ with regenerative capacity and is essential for maintaining the body homeostasis. Under pathological conditions, such as chronic hepatitis, liver cirrhosis and so on, the impairment of liver regeneration can lead to insufficient liver function or even liver failure. Therefore, promoting liver regeneration can improve the patient's prognosis. Prostaglandin E2 is a hormone-like messenger with physiological activity that can promote tissue regeneration. This article reviews the metabolism and transport pathways of prostaglandin E2 and its mechanism of action in liver tissue regeneration, and proposes that prostaglandin E2 is an important cytokine involved in the liver regeneration process, and has potential clinical application prospects for the treatment of liver injury.

[Cytocompatibility of angiogenesis-promoting acidified silk protein sponge matrices and its effects on wound healing of full-thickness skin defects in rats].

Objective: To analyze the mechanism of acidified silk protein sponge matrices and methanolized silk protein sponge matrices in promoting wound healing. Methods: The experimental method was conducted. Acidified silk protein sponge matrices with vascularization ability and methanolized silk protein sponge matrices without vascularization ability were prepared by improved freeze-drying method. General observation was performed. Internal morphology was observed with scanning electron microscope. The secondary structure was observed with X-ray diffractometer (XRD) and infrared spectrometer. Compressive modulus was tested by tensile machine. Two 3-week-old male Sprague-Dawley (SD) rats were used to isolate bone marrow mesenchymal stem cells (BMSCs) cultured in above-mentioned two silk protein sponge matrices, the number of cells was counted under laser scanning confocal microscope after 1, 6 days of culture. Four full-thickness skin defect wounds were made on each one of twelve 8-week-old male SD rats, which were divided into methanolized silk group (24 wounds) and acidified silk group (24 wounds) covered with the corresponding silk protein sponge matrices. On post operation day (POD) 3, 7, 10, and 14, general observation was performed and the remaining wound area was recorded. On POD 3, 7, and 14, the wounds and marginal tissue were collected for hematoxylin-eosin staining (HE) staining and Masson staining to observe growth of new tissue and collagen deposition and CD34 immunohistochemical staining to observe vascularization. Sample number of each index of each group at every time point in animal experiment was 6. Data were statistically analyzed with analysis of variance of factorial design, analysis of variance for repeated measurement, independent-samples t test, and Bonferroni correction. Results: Methanolized silk protein sponge matrices and acidified silk protein sponge matrices had the same composition and similar porous structure, with pore size of 300-500 µm. XRD showed that methanolized silk protein sponge matrices showed a significant crystallization peak, while acidified silk protein sponge matrices was mainly composed of amorphous structure. Infrared spectrometer showed that acidified silk protein sponge matrices appeared a strong absorption peak at 1 650 cm(-1), and the methanolized silk protein sponge matrices appeared a strong absorption peak at 1 630 cm(-1). Compressive modulus of methanolized silk protein sponge matrices was (23.8±1.3) kPa, which was significantly higher than (6.1±0.9) kPa of acidified silk protein sponge matrices (t=19.550, P<0.01). After one day of culture, BMSCs successfully adhered to the two kinds of silk protein sponge matrices, and the cells were not spread. After six days of culture, BMSCs were spread on the two kinds of silk protein sponge matrices, and the number of cells on the acidified silk protein sponge matrices increased significantly. On POD 3, the wounds of the 2 groups did not shrink significantly. On POD 7, the wound area in acidified silk group was significantly smaller than that in methanolized silk group, and new epithelium growth occurred at the wound edge. On POD 14, the wounds of acidified silk group basically healed, and the wounds of methanolized silk group were dry and shrinked significantly. Remaining wound area of acidified silk group on POD 3, 7, 10, and 14 were significantly smaller compared with that in methanolized silk group ( t=7.782, 10.620, 3.707, 6.830, P<0.05 or P<0.01). HE staining, Masson staining, and CD34 immunohistochemical staining showed on POD 3, new tissue growing into silk protein sponge matrices of wounds of acidified silk group was more than that in methanolized silk group, the former group secreted a small amount of collagen, collagen formation was not observed in the latter group, the number of vascular endothelial cells migrated into the matrices were more in the former group than the latter group; on POD 7, the area of new tissue covering matrices hole of wounds of acidified silk group was larger than that in methanolized silk group, collagen in the former group was more than that in the latter group and was evenly distributed, the number of blood vessels in the former group was more than that on POD 3, and the new blood vessels in the latter group were scattered; on POD 14, the new tissue in acidified silk group was similar in structure to normal skin tissue and formed a certain thickness, the new tissue in methanolized silk group basically grew into the matrices, the former group had rich collagen deposition, the latter group had scattered collagen, and blood vessels in the former group distributed uniformly and density of blood vessels was significantly higher than that in the latter group ((55.7±6.0) and (34.1±1.0) pieces/mm(2), respectively, t=9.042, P<0.01). Conclusions: Angiogenesis-promoting acidified silk protein sponge matrices have good cytocompatibility, which can facilitate the rapid formation of vascular network in wound area, providing sufficient blood supply to accelerate the tissue regeneration and collagen deposition, thereby promoting wound healing and improving healing quality, these effects are better than methanolized silk protein sponge matrices.

[A prospective randomized controlled clinical study on the treatment of hypertrophic scar after burn by fractional carbon dioxide laser combined with autologous fat injection].

Objective: To explore the clinical effects of fractional carbon dioxide laser combined with autologous fat injection in the treatment of hypertrophic scar after burn. Methods: From April 2018 to April 2019, 12 patients with hypertrophic scar after burn who met the inclusion criteria were admitted to the Department of Plastic Surgery and Burns of Xuzhou Renci Hospital, and were included in this prospective randomized controlled clinical study. There were 7 males and 5 females with age of (32±11) years and scar area of (612±195) cm(2). One scar was selected from each patient and divided into two equal area scars, and they were divided into combined treatment group and laser alone group with 12 scars in each group according to the random number table. The scar in laser alone group was only treated with fractional carbon dioxide laser, while the scar in combined treatment group was injected with autologous granular fat and then treated with fractional carbon dioxide laser. Scars in the two groups were treated once every 2 months, totally 3 times. Before the first treatment and 6 months after the last treatment, the scars in the two groups were evaluated by modified Vancouver Scar Scale (mVSS), hematoxylin-eosin staining and color Doppler ultrasound. Six months after the last treatment, the curative effect of scars in the two groups was evaluated, and the effective number of scar treatment was calculated. The adverse reactions during the whole treatment were recorded. Data were statistically analyzed with independent sample t test, paired sample t test, and McNemar exact probability method test. Results: Six months after the last treatment, the mVSS score of scars in combined treatment group was (4.5±0.4) points, which was significantly lower than (7.8±0.6) points in laser alone group (t=10.000, P<0.01). Six months after the last treatment, the mVSS scores of scars in combined treatment group and laser alone group were significantly lower than those before the first treatment ((13.5±0.7) and (13.8±0.6) points, t=8.805, 9.010, P<0.01). The effective number of scar treatment in combined treatment group was significantly more than that in laser alone group (P<0.05). There was no scar aggravation, infection, or other adverse reactions during the treatment of scars in both groups. Before the first treatment, the scars in both groups had large collagen, disordered arrangement, proliferation of capillaries, infiltration of some inflammatory cells, and disappearance of skin appendages. Six months after the last treatment, the scar collagen in both groups was sparse and orderly arranged, and the vascular density was reduced. The improvement of scars in combined treatment group was more obvious than that of laser alone group. Six months after the last treatment, the scar thickness in combined treatment group was significantly smaller than that in laser alone group (t=2.657, P<0.05). Before the first treatment, the blood flow of scars in both groups was abundant; 6 months after the last treatment, the blood flow of scars in combined treatment group was significantly less than that in laser alone group. Conclusions: Fractional carbon dioxide laser combined with autologous fat injection in the treatment of hypertrophic scar after burn can significantly reduce the pain and itching symptoms of scar, and improve the thickness, texture, and congestion of scar. The combined treatment has synergistic effect and less adverse reactions, providing a more effective treatment for patients with hypertrophic scar.

[Influence of porcine urinary bladder matrix and porcine acellular dermal matrix on wound healing of full-thickness skin defect in diabetic mice].

Objective: To compare the difference of pro-healing effect of porcine urinary bladder matrix (UBM) and porcine acellular dermal matrix (ADM) on full-thickness skin defect wounds in diabetic mice. Methods: Thirty-six type 2 diabetic BKS db/db mice aged 10 weeks were divided into UBM group and ADM group according to the random number table, with 18 mice in each group and preoperative molarity of non-fasting blood glucose higher than 16.6 mmol/L. A circular full-thickness skin defect wound with 6 mm in diameter was made on the back of each mouse, and porcine UBM and porcine ADM scaffolds were implanted into the wounds of both groups correspondingly. Immediately after operation and on post operation day (POD) 7, 14, and 28, wounds were observed generally. On POD 7, 14, and 28, 6 mice of each group were collected respectively to calculate the rate of wound epithelialization, and then the corresponding mice were sacrificed after calculation, and the wound tissue was harvested to make slices. Six slices of the mice in the 2 groups on POD 7 and 14 were respectively collected to stain with haematoxylin-eosin (HE), and 6 slices on POD 7 and 28 had Masson's staining, which were used to observe histopathological changes and scaffold degradation. On POD 7 and 14, 24 slices of each mouse in the 2 groups were collected respectively to detect alpha smooth muscle actin (α-SMA) and CD31 positive expression denoting the growth of myofibroblasts and neovessels respectively and observe the distribution and activation of macrophages with immunohistochemical staining. The wound tissue of mice in the 2 groups on POD 7 and 14 was harvested to detect mRNA expressions of fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor ß(1) (TGF-ß(1)) by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The sample number of above-mentioned indexes in each group at each time point was 6. Data were statistically analyzed with analysis of variance for factorial design, t test, and Bonferroni correction. Results: (1) General observation showed that integration of UBM scaffold into the wounds of mice in UBM group on most time points was superior, and integration of ADM scaffold into the wounds of mice in ADM group on most time points was inferior. On POD 28, epidermis still did not form in some region of scaffold surface of wounds of mice in ADM group, while wounds of mice in UBM group were completely epithelialized. On POD 7, 14, and 28, wound epithelialization rates of mice in UBM group were respectively (22.4±6.4)%, (68.6±12.4)%, and 100.0%, all significantly higher than (4.5±2.2)%, (23.6±4.6)%, and (64.2±13.2)% in ADM group (t=7.427, 9.665, 7.655, P<0.01). (2) HE staining and Masson's staining showed that a large number of cells appeared in wound scaffold of mice in UBM group on POD 7; cells distributed in the whole region of UBM scaffold on POD 14; dermal tissue with structure similar to normal skin formed in the wounds and the fibrous morph of UBM scaffolds disappeared on POD 28. Only a small number of cells appeared in inside of wound scaffolds of mice in ADM group on POD 7; on POD 14, cells were sparsely distributed in ADM scaffolds; on POD 28, the morph of originally robust collagen fiber of ADM scaffolds was still clear and visible. (3) On POD 7, a large number of accumulated myofibroblasts and neovessels appeared in the lower layers of scaffolds of wounds of mice in UBM group; on POD 14, evenly distributed myofibroblasts and neovessels appeared in the upper layers of UBM scaffolds, and most vessels were perfused. On POD 7 and 14, myofibroblasts were sparsely distributed in scaffolds of wounds of mice in ADM group with no or a few neovascular structures perfused unobviously. On POD 7 and 14, α-SMA positive expressions in scaffolds of wounds of mice in UBM group were significantly higher than those in ADM group (t=25.340, 6.651, P<0.01); CD31 positive expressions were also significantly higher than those in ADM group (t=34.225, 10.581, P<0.01). (4) On POD 7, a large number of macrophages appeared in the lower layers of scaffolds of wounds of mice in UBM group; on POD 14, macrophages infiltrated into the internal region of UBM scaffolds, and M2 polarization occured without M1 polarization. On POD 7, a small number of macrophages appeared in the bottom of scaffolds of wounds of mice in ADM group; on POD 14, macrophages were few in internal region of ADM scaffold, and neither M2 polarization nor M1 polarization occurred. (5) On POD 7 and 14, mRNA expressions of FGF-2, VEGF, PDGF, and TGF-ß(1) in the wound tissue of mice in UBM group were all significantly higher than those in ADM group (t=7.007, 14.770, 10.670, 8.939; 7.174, 7.770, 4.374, 4.501, P<0.01). Conclusions: Porcine UBM scaffold is better than porcine ADM in facilitating wound repair and dermis reconstruction of full-thickness skin defects in diabetic mice through the induction of myofibroblasts and macrophages immigration, the promotion of neovascularization and expression of pro-healing growth factors.

[Clinical efficacy and influencing factors of different modes of continuous negative pressure wound therapy on venous ulcer wounds of lower limbs].

Objective: To explore the clinical efficacy of different modes of continuous negative pressure wound therapy (NPWT) on venous ulcer wounds of lower limbs, and to analyze the influencing factors. Methods: From January 2018 to December 2019, 53 patients with venous ulcer of lower limbs who met the inclusion criteria and hospitalized in the Affiliated Hospital of Jiangnan University were recruited in this prospective randomized controlled study. According to the random number table, the patients were divided into single negative pressure therapy (SNPT) group (19 patients, 11 males and 8 females), cyclic alternating negative pressure therapy (CANPT) group (17 patients, 12 males and 5 females), and routine dressing change (RDC) group (17 patients, 10 males and 7 females), aged (47±11), (49±10), and (47±10) years respectively. After admission, patients in SNPT group were given continuous NPWT with the single negative pressure setting at -13.3 kPa, patients in CANPT group were also given continuous NPWT but with the cyclic alternating negative pressure setting from -16.0 to -10.7 kPa, while patients in RDC group were given dressing change with vaseline gauze soaked with iodophor. The wound healing rate was calculated on treatment day 7 and 14. Transcutaneous oxygen pressure (TcPO(2)) around the wound was detected by TcPO(2) meter before treatment and on treatment day 7 and 14. The wound exudate/drainage fluid was collected on treatment day 1, 4, 7, 10, and 14, with the pH value measured using a pH meter, and the volume of exudate/drainage fluid recorded. Before treatment and on treatment day 7 and 14, venous blood was collected to detect the serum levels of interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α(TNF-α), transforming growth factor-ß(1) (TGF-ß(1)), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Before treatment and on treatment day 7 and 14, wound exudates were collected for bacterial culture, and Visual Analogue Scale and Hamilton Anxiety Scale were used to evaluate the degree of wound pain and anxiety of patients respectively. The length of hospital stay and the total treatment cost were counted. Analysis of variance for repeated measurement, one-way analysis of variance, least significant difference test, Kruskal Wallis H test, Mann Whitney U test, chi-square test, Fisher's exact probability method test, and Bonferroni correction were used to analyze the data. According to the wound healing rate on treatment day 14, the efficiency of patients were divided into two grades of significant healing with wound healing rate≥70% and non significant healing with wound healing rate<70%. According to the two categories of wound healing rate as dependent variables, the levels of TcPO(2), IL-1ß, IL-6, TNF-α, TGF-ß(1), VEGF, bFGF levels and bacterial detection, wound pain and anxiety before treatment, wound exudate/drainage fluid volume and pH value on treatment day 1 were taken as covariates, and binary classification multifactor logistic regression analysis was used to analyze the risk factors of significant wound healing. Results: (1) On treatment day 7, the wound healing rate of patients in SNPT group was (33±10) %, which was significantly higher than (24±9) % of RDC group (P<0.05). On treatment day 14, the wound healing rates of patients in SNPT group and CANPT group were (71±15)% and (66±18)%, respectively, which were significantly higher than (45±19)% of RDC group (P<0.01). (2) Compared with those of RDC group, the TcPO(2) value around the wound of patients was significantly increased in SNPT group on treatment day 14 and in CANPT group on treatment day 7 and 14 (P<0.05 or P<0.01), the pH value of wound drainage fluid of patients was significantly decreased in SNPT group on treatment day 10 and 14 and in CANPT group on treatment day 7 and 14 (P<0.05), the volume of wound drainage fluid of patients was significantly reduced in SNPT group on treatment day 10 and 14 and in CANPT group on treatment day 7, 10, and 14 (Z=-4.060, -4.954, -2.413, -4.085, -4.756, P<0.05 or P<0.01), the serum levels of IL-1ß, IL-6, and TNF-α of patients were significantly decreased in SNPT group and CANPT group on treatment day 7 and 14 (P<0.01), the serum level of TGF-ß(1) of patients was significantly increased in CANPT group on treatment day 14 (P<0.05), the serum levels of VEGF and bFGF were significantly increased in SNPT group and CANPT group on treatment day 14 (P<0.01), the bacteria detection proportion of wound exudate, wound pain, and anxiety scores of patients were significantly decreased in SNPT group and CANPT group on treatment day 7 and 14 (P<0.01). Compared between the negative pressure therapy two groups, except the wound pain score of patients in CANPT group was significantly lower than that in SNPT group (P<0.01) on treatment day 7, the other indicators mentioned above were similar. (3) The length of hospital stay of patients in SNPT group was similar to that in CANPT group (P>0.05), which were significantly shorter than the time in RDC group (P<0.01). The total treatment cost of patients among the three groups was similar (F=1.766, P>0.05). (4) Before treatment, the serum levels of TNF-α and bFGF, TcPO(2) around the wound, and the degree of wound pain were risk factors for significant wound healing (odds ratio=1.109, 0.950, 1.140, 2.169, 95% confidence interval=1.012-1.217, 0.912-0.988, 1.008-1.290, 1.288-3.651, P<0.05 or P<0.01). Conclusions: Clinical application of continuous NPWT under single negative pressure mode and cyclic alternating negative pressure mode has a positive effect on improving the wound base and healing rate of venous ulcer of lower limbs. But cyclic alternating negative pressure mode is significantly more effective than single negative pressure mode in improving TcPO(2) around the wound, reducing wound pH value, reducing exudate volume and relieving pain. The serum levels of TNF-α and bFGF, TcPO(2) around the wound and the degree of wound pain were the risk factors that affect the wound healing significantly.

Long noncoding RNA PART1 restrains aggressive gastric cancer through the epigenetic silencing of PDGFB via the PLZF-mediated recruitment of EZH2.

Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF) is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFRß/PI3K/Akt signaling pathway. Based on these findings, we showed PART1 plays a tumor suppressor role by promoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression.

[Normative application of negative-pressure wound therapy to improve the wound repair level].

In recent 20 years, the technology of negative-pressure wound therapy (NPWT) has been widely used in the field of wound repair. Basic research and clinical application have proved that NPWT plays a positive role in regulating wound repair in many aspects. Compared with the previous 10 years, NPWT has made great progress in the last 10 years in negative pressure materials or equipment, as well as in the use method, mechanism research, and clinical application strategy. Strict and accurate grasp of the clinical application indication of NPWT and scientific application of NPWT to regulate the microenvironment of wound healing, effective improvement of the healing quality of different types of wounds, and further improve the level of wound repair are the core principles of the normative use of NPWT.