Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

[Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province].

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

[Analysis of the clinical confusion and controversy of esophagogastric junction tumor from basic anatomy].

There are still many controversies in the surgical treatment of esophagogastric junction tumors in terms of surgical approach, cleaning range, and resection scope. The reason is the confusion about the scope of the esophagogastric junction. The previous domestic and foreign anatomy descriptions of this part are not enough to solve the current problems. Based on a large number of basic anatomy and clinical operations, this article proposes that the esophagogastric junction may be wrapped by a complete and separate esophagogastric junction membrane with independent anatomy other than infracardiac bursa. The structure of the transitional tissue, mainly from the distribution of submucosal veins, explained the relationship and significance of tissue transitional changes and clinical operations, and made a reasonable analysis of the current controversy based on the anatomical characteristics, which is worthy of further investigation.

[Short-term outcomes of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with spondyloepiphyseal dysplasia].

OBJECTIVE: Severe hip osteoarthritis, caused by bone or joint maldevelopment, biomechanical transformation and previous surgical intervention, is inclusively existed in spondyloepiphyseal dysplasia (SED). To investigate and discuss the short-term efficacy and possible effects of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with SED. METHODS: From January 2017 to June 2019, 374 patients with hip osteoarthritis were involved for total hip arthroplasty conducted by senior professional surgeons, of whom 9 patients (6 males and 3 females) with 12 hip osteoarthritis secondary to the SED met the inclusive and exclusive criteria and received the above-mentioned hip operation. The short-term outcomes were observed. RESULTS: All the patients were implanted with Johnson & Johnson ceramic on ceramic cementless hip prostheses within the arthroplasty. They were followed up for an average period of 20 months. Except for one muscular calf vein thrombosis case, no complications, such as aseptic loosening, joint dislocation, fracture, neurovascular injury, deep vein thrombosis and infection were observed in all the 9 patients. Before the surgery, the average Harris hip score was 35.55, while the average of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was 56.56. The level of quality of life indicated by SF-12 score was 41.56 on average. The mean pre-operation visual analogue scale (VAS) was 7.44. At the last follow-up, the average Harris hip score increased to 89.56, whereas the average WOMAC declined to 41.11. Compared with the baseline point, the average SF-12 score went up to 56.33. Dramatic drop of the mean VAS value to 2.67 was also observed at the last follow-up. In addition, post-operative increase of several pelvic-related parameters including pelvic incidence, pelvic tilt and sacral slope could be observed in the SED patients. The average measured pelvic incidence, pelvic tilt and sacral slope were 68.95°±4.60°, 52.75°±1.06° and 17.45°±1.77° before operation, respectively; whilst the mean value of these specific parameters increased to 76.98°±5.12°, 60.51°±4.35° and 18.10°±2.02°, respectively. The even leg lengths of the lower extremities were obtained after total hip arthroplasty. CONCLUSION: Total hip arthroplasty is satisfactory in the short-term pain relieve and function recovery for the management of Tönnis grade 3 hip osteoarthritis secondary to the SED.

[Recommendations for general surgery clinical practice in 2019 coronavirus disease situation].

The 2019 coronavirus disease(COVID-19) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the COVID-19 as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight against COVID-19.

[Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation].

Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.

[Clinical study on two reconstruction methods of proximal gastrectomy and piggyback jejunal interposition for Siewert â ¡ or â ¢ adenocarcinoma of esophagogastric junction].

Objective: To evaluate the clinical efficacy of two different digestive tract reconstruction methods in the Siewert Ⅱ or Ⅲ adenocarcinoma of esophagogastric junction underwent proximal gastrectomy and piggyback jejunal interposition. Methods: A total of 84 patients with Siewert Ⅱ or Ⅲ AEG who underwent proximal gastrectomy and interposition jejunal anastomosis were enrolled prospectively according to the exclusion criteria, from October 2015 to August 2017 at Department of Digestive Minimally Invasive Surgery, Shanxi Cancer Hospital. There were 61 male and 23 female patients, aged 48-69 years with an average age of 59.7 years. They were divided into single-tract reconstruction group (n=41) and double-tract reconstruction group (n=43) according to random number table. Both groups underwent proximal gastrectomy and piggyback jejunal interposition. After side-to-side anastomosis of the remnant stomach and jejunum was performed in the single-tract group, jejunum 3 cm below the anastomosis was ligated or closed. The jejunum in the double-tract group was not treated during the operation. Relevant nutritional indicators were collected at 3 months and 6 months after operation. The data were analyzed by repeated measurement of variance analysis to determine the nutritional status. Results: There was no significant difference in preoperative general condition between single-tract reconstruction group and double-tract reconstruction group (P>0.05). There was no significant difference in perioperative related indicators (P>0.05). Nutritional indicators in single-channel reconstruction group were higher than those in double-channel reconstruction group (hemoglobin: F=23.374, P=0.000; albumin: F=6.149, P=0.003; total protein: F=18.362, P=0.000; weight: F=74.255, P=0.000). The quality of life was compared half year after operation, there was no significant difference in the incidence of subjective symptoms such as reflux, heart burning, nausea and vomiting, dysphagia and sternum discomfort in the two groups (P>0.05), as well as the results of QLQ-STO22 score (27.0±3.8 vs. 27.6±3.3, t=-0.688, P=0.494). The results of gastroscopy showed that the incidence and degree of the two groups were almost the same whether in the incidence of reflux esophagitis (2/41 vs. 2/43, P=1) or in the contrast of reflux degree (Z=-1.528, P=0.127). Conclusion: For patients with type Siewert Ⅱ or Ⅲ esophagogastric junction adenocarcinoma who underwent proximal gastrectomy and piggyback jejunal operation, single tract reconstruction is ideal.

[Laparoscopic versus open surgery for gastric gastrointestinal stromal tumors in unfavorable location: a propensity score-matching analysis].

Objective: To investigate the efficacy and feasibility of laparoscopic resection for gastric gastrointestinal stromal tumor (GIST) in unfavorable location by comparing with open surgery. Methods: Clinicopathological and follow-up data of 176 patients with gastric GIST in unfavorable location admitted at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to December 2017 were analyzed retrospectively. There were 94 males and 82 females, aging of (57.4±12.7) years (range: 20-90 years). Of the 176 patients, 64 underwent laparoscopic surgery (laparoscopic group) and 112 underwent open surgery (open group). One-to-one propensity score matching (PSM) was performed to balance the covariance between laparoscopic group and open surgery group. Before PSM, the differences between the two group in tumor size and modified National Institutes of Health risk classification were significant. After PSM, there were 63 pairs (63 cases in laparoscopic group and 63 cases in open group) and the baseline characteristics were comparable between the two groups(P>0.05). The difference of short-term outcome between the two groups were compared using t test, χ(2) test or Wilcoxon rank-sum test. The survival curve was established by Kaplan-Meier method and the Log-rank test was used to compare the survival of the two groups. Results: The operation time of laparoscopic group was shorter ((141.6±100.6) minutes vs. (100.4±67.7) minutes, t=2.681, P=0.008), the hospitalization cost was higher ((5.2±0.7) ten thousand yuan vs. (4.2±0.8) ten thousand yuan, t=7.357, P=0.000) than open group. The time to first flatus ((49.1±8.2) hours vs. (71.0±4.6) hours, t=-18.482, P=0.000) and preoperative hospital stay ((10.3±6.0) days vs. (14.8±7.6) days, t=-3.717, P=0.000) was shorter in laparoscopic group. With a median follow-up time of 44 months (range: 10 to 154 months), the 1-, 3-, 5-year relapse-free survival rates in the laparoscopic group and open group were 98.3%, 92.1%, 92.1% and 100%, 86.3%, 83.2%, respectively (χ(2)=0.696, P=0.404). The 1-, 3-, 5-year overall survival rates in the laparoscopic group and open group were 96.6%, 94.7%, 94.7% and 100%, 91.1%, 81.4%, respectively (χ(2)=0.366, P=0.545). Conclusions: In experienced medical centers, laparoscopic resection is safe and feasible for GIST in unfavorable location. Compared to open surgery, laparoscopic resection achieves a faster postoperative recovery and a similar long-term prognosis.

ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation.

Organ transplantation from ABO blood group-incompatible (ABOi) donors requires accurate detection, effective removal and subsequent surveillance of antidonor antibodies. Because ABH antigen subtypes are expressed differently in various cells and organs, measurement of antibodies specific for the antigen subtypes in the graft is essential. Erythrocyte agglutination, the century-old assay used clinically, does not discriminate subtype-specific ABO antibodies and provides limited information on antibody isotypes. We designed and created an ABO-glycan microarray and demonstrated the precise assessment of both the presence and, importantly, the absence of donor-specific antibodies in an international study of pediatric heart transplant patients. Specific IgM, IgG, and IgA isotype antibodies to nonself ABH subtypes were detected in control participants and recipients of ABO-compatible transplants. Conversely, in children who received ABOi transplants, antibodies specific for A subtype II and/or B subtype II antigens-the only ABH antigen subtypes expressed in heart tissue-were absent, demonstrating the fine specificity of B cell tolerance to donor/graft blood group antigens. In contrast to the hemagglutination assay, the ABO-glycan microarray allows detailed characterization of donor-specific antibodies necessary for effective transplant management, representing a major step forward in precise ABO antibody detection.

Imaging Tolerance Induction in the Classic Medawar Neonatal Mouse Model: Active Roles of Multiple F1-Donor Cell Types.

The immature immune system is uniquely susceptible to tolerance induction and thus an attractive target for immunomodulation strategies for organ transplantation. Newborn mice injected with adult semi-allogeneic lymphohematopoietic cells accept transplants without immunosuppressive drugs. Early in vivo/in situ events leading to neonatal tolerance remain poorly understood. Here, we show by whole body/organ imaging that injected cells home to lymphoid organs and liver where various F1-donor cell types selectively alter neonatal immunity. In host thymus, F1-donor dendritic cells (DC) interact with developing thymocytes and regulatory T cells suggesting a role in negative selection. In spleen and lymph nodes, F1-donor regulatory T/B cells associate with host alloreactive cells and by themselves prolong cardiac allograft survival. In liver, F1-donor cells give rise to albumin-containing hepatocyte-like cells. The neonatal immune system is lymphopenic, Th-2 immunodeviated and contains immature DC, suggesting susceptibility to regulation by adult F1-donor cells. CD8a T cell inactivation greatly enhances chimerism, suggesting that variable emerging neonatal alloreactivity becomes a barrier to tolerance induction. This comprehensive qualitative imaging study systematically shows contribution of multiple in vivo processes leading simultaneously to robust tolerance. These insights into robust tolerance induction have important implications for development of strategies for clinical application.

Chemical Basis for Qualitative and Quantitative Differences Between ABO Blood Groups and Subgroups: Implications for Organ Transplantation.

Blood group ABH(O) carbohydrate antigens are carried by precursor structures denoted type I-IV chains, creating unique antigen epitopes that may differ in expression between circulating erythrocytes and vascular endothelial cells. Characterization of such differences is invaluable in many clinical settings including transplantation. Monoclonal antibodies were generated and epitope specificities were characterized against chemically synthesized type I-IV ABH and related glycans. Antigen expression was detected on endomyocardial biopsies (n = 50) and spleen (n = 11) by immunohistochemical staining and on erythrocytes by flow cytometry. On vascular endothelial cells of heart and spleen, only type II-based ABH antigens were expressed; type III/IV structures were not detected. Type II-based ABH were expressed on erythrocytes of all blood groups. Group A1 and A2 erythrocytes additionally expressed type III/IV precursors, whereas group B and O erythrocytes did not. Intensity of A/B antigen expression differed among group A1 , A2 , A1 B, A2 B and B erythrocytes. On group A2 erythrocytes, type III H structures were largely un-glycosylated with the terminal "A" sugar α-GalNAc. Together, these studies define qualitative and quantitative differences in ABH antigen expression between erythrocytes and vascular tissues. These expression profiles have important implications that must be considered in clinical settings of ABO-incompatible transplantation when interpreting anti-ABO antibodies measured by hemagglutination assays with reagent erythrocytes.

Identification of potential therapeutic targets for melanoma using gene expression analysis.

Metastatic melanoma represents a significant cause of death in patients with melanoma and the frequency is increasing. The aim of this study was to identify potential therapeutic targets for metastatic melanoma. Gene expression profile GSE44660 was downloaded from Gene Expression Omnibus database. A total of 22 samples were analyzed in our study, including 3 specimens of normal melanocytes, 12 specimens of melanoma LNM (lymph node metastasis) and 7 specimens of MBM (melanoma brain metastasis). DEGs (differentially expressed genes) in LNM and MBM were identified respectively using Limma package. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways analyses of common DEGs between two comparison groups were performed using DAVID, followed by cancer-related genes and transcription factor analysis. PPI (protein-protein interaction) network was constructed by STRING, and significant key genes were selected. Totally, 401 common DEGs were identified. Disease analysis showed that ICAM1 (intercellular adhesion molecule 1) and NBN (nibrin) were related to melanoma. In the PPI network, BIRC5 (baculoviral IAP repeat containing 5), BUB1 (BUB1 mitotic checkpoint serine/threonine kinase), GMNN (geminin, DNA replication inhibitor), AURKA (aurora kinase A), TOP2A (topoisomerase (DNA) II alpha) and BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) were with higher degree more than 50. ICAM1, NBN, BIRC5, BUB1, BUB1B, GMNN, AURKA and TOP2A may play key roles in the progression and development of melanoma. They may be used as specific therapeutic targets in the treatment of metastatic melanoma. However, further experiments are still needed to confirm our results.

[Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection].

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (ß [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

[Effect and mechanism of human adipose-derived stem cell exosomes on diabetic peripheral neuropathy].

Objective: To investigate the changes of artemin protein expression in diabetic peripheral neuropathy (DPN) and to explore the regulatory effect of human adipose-derived stem cell (ADSC) exosomes on the change of artemin protein expression. Methods: This research was a prospective observational clinical research combined with experimental research. Thirteen DPN patients (9 males and 4 females, aged 32 to 68 years) who were admitted to the First Affiliated Hospital of Air Force Medical University (hereinafter referred to as our hospital) from May 2022 to October 2023 and met the inclusion criteria were selected as DPN group, and 5 non-diabetes patients (4 males and 1 female, aged 29 to 61 years) who were admitted to our hospital in the same period of time and met the inclusion criteria were selected as control group. The toe nerve or sural nerve tissue in the abandoned tissue after debridement or amputation of patients in the two groups was collected. The pathological changes of nerve tissue were observed after hematoxylin-eosin staining; the protein expressions of S100ß and artemin in nerve tissue were observed after immunofluorescence staining, and the artemin protein expression was quantified; the protein and mRNA expressions of artemin were detected by Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction, respectively (the sample number in DPN group and control group was 13 and 5, respectively). Twelve male C57BL/6 mice aged 3 to 5 days were collected to isolate Schwann cells, and the cells were divided into conventional culture group cultured routinely, high glucose alone group (cultured with high concentration of glucose solution only), and high glucose+exosome group (cultured with high concentration of glucose solution and extracted human ADSC exosomes). After 24 hours of culture, the cell proliferation activity was detected by cell counting kit 8 (n=6). After 48 hours of culture, the protein expression of artemin was detected by Western blotting (n=3). Results: Compared with those in control group, the neural supporting cells decreased and the inflammatory cells increased in the nerve tissue of patients in DPN group, showing typical manifestations of nerve injury. Immunofluorescence staining showed that compared with those in control group, the nuclei was more, and the protein expression of S100ß was lower in nerve tissue of patients in DPN group. The protein expression of artemin in nerve tissue of patients in DPN group was 71±31, which was significantly lower than 1 729±62 in control group (t=76.92, P<0.05). Western blotting detection showed that the protein expression of artemin in nerve tissue of patients in DPN group was 0.74±0.08, which was significantly lower than 0.97±0.06 in control group (t=5.49, P<0.05). The artemin mRNA expression in nerve tissue of patients in DPN group was significantly lower than that in control group (t=7.65, P<0.05). After 24 hours of culture, compared with that in conventional culture group, the proliferation activities of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the proliferation activity of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). After 48 hours of culture, compared with those in conventional culture group, the protein expressions of artemin of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the protein expression of artemin of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). Conclusions: The protein expression of artemin in nerve tissue of DPN patients is lower than that in normal nerve tissue, which may be related to the reduction of proliferation activity of Schwann cells by high glucose. Human ADSC exosomes may improve the proliferation activity of Schwann cells by increasing artemin protein expression, thereby delaying the progression of DPN.

[Research advances on the role of Schwann cells in diabetic peripheral neuropathy].

Diabetic peripheral neuropathy (DPN) is one of the common chronic complications of diabetes, resulting in neuropathy of spinal nerve, cranial nerve, and vegetative nerve. Diabetic distal symmetric multiple neuropathy is the most representative lesion of DPN, including symptoms of bilateral limbs pain, numbness, and paresthesia, etc. DPN is one of the main reasons causing diabetic foot ulcer (DFU). Schwann cells (SCs) are the primary glia cells of the peripheral nervous system, which play very important role in repairing after nerve injury. As the target cells of chronic hyperglycemia, SCs' functions, including the formation of myelin sheath, the secretion of neurotrophic factors, energy supplying for the axon, and the guidance of axon regeneration, etc., are damaged under the action of high glucose. The destroyed functions of SCs can inhibit the repair of damaged nerves and accelerate the progress of DPN. Therefore, if the damage of high glucose to SCs can be effectively reduced, it will provide a new way for the treatment of DPN and DFU and reduce the morbidity of DFU. This review focuses on the function of SCs and its relationship with DPN.

[A prospective randomized controlled study of antibiotic bone cement in the treatment of diabetic foot ulcer].

Objective: To investigate the clinical effects and related mechanism of antibiotic bone cement in treating diabetic foot ulcer (DFU). Methods: A prospective randomized controlled study was conducted. From August 2020 to August 2022, 24 patients with DFU who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. According to the block randomization, the patients were divided into 2 groups, with 12 patients in each group. In antibiotic bone cement group, there were 7 male and 5 female patients, aged (64±8) years, with the ulcer area of (41±21) cm2. In silver sulfadiazine group, there were 8 male and 4 female patients, aged (62±8) years, with the ulcer area of (38±19) cm2. Under the condition of ensuring the patency of at least one main inferior genicular artery in each patient, the continuous vacuum sealing drainage was performed for 3-5 days after thorough debridement. Thereafter, the wounds in antibiotic bone cement group were treated with gentamicin-laden bone cement, and the wounds in silver sulfadiazine group were treated with silver sulfadiazine cream for dressing change. After 3 weeks of dressing change, the wound was covered with split-thickness skin graft from the lateral thigh on the affected side. Before debridement and after 3 weeks of dressing change, the blood flow intensities of wound tissue and normal skin tissue in foot were measured using laser Doppler flowmeter, and then, the percentage of relative blood flow intensity of wound and the change rate of blood flow intensity were calculated. After 3 weeks of dressing change, the wound margin tissue was taken, the number of CD31-positive neovascular and the vascular morphology were observed and detected by immunohistochemical staining, the morphology of blood vessels surrounded by CD31 and α-smooth muscle actin (α-SMA) double-positive cells was observed by immunofluorescence staining, the cell proliferation activity was evaluated by immunofluorescence staining (denoted as the ratio of Ki67 positive cells), and the protein expression of vascular endothelial growth factor receptor 2 (VEGFR2) was detected by Western blotting. The skin graft survival was observed 3-5 days after skin grafting, and the wound healing time was recorded. Data were statistically analyzed with independent sample t test and Fisher's exact probability test. Results: The percentages of relative blood flow intensity of wounds of patients before debridement were similar between the two groups (P>0.05). After 3 weeks of dressing change, the percentage of relative blood flow intensity of wounds and the change rate of blood flow intensity of patients in antibiotic bone cement group were (44.7±2.0)% and (129±12)%, respectively, which were significantly higher than (28.3±1.2)% and (41±8)% in silver sulfadiazine group (with t values of 24.15 and 20.97, respectively, P<0.05). After 3 weeks of dressing change, compared with those in silver sulfadiazine group, the number of CD31-positive neovascular in the wound margin tissue of patients in antibiotic bone cement group was significantly increased (t=33.81, P<0.05) with larger diameter and more regular arrangement, the vascular wall continuity surrounded by CD31 and α-SMA double-positive cells was better, and the ratio of Ki67 positive cells and protein expression of VEGFR2 were significantly increased (with t values of 40.97 and 47.38, respectively, P<0.05). On post skin grafting day 3-5, all the patients in antibiotic bone cement group and 8 patients in silver sulfadiazine group had good skin graft survival, while 4 patients in silver sulfadiazine group showed spotted/patchy skin graft necrosis, which were cured after corresponding treatment. The wound healing time of patients in antibiotic bone cement group was (47.1±2.9) d, which was significantly shorter than (58.8±2.3) d in silver sulfadiazine group (t=10.86, P<0.05). Conclusions: Compared with silver sulfadiazine, clinical application of antibiotic bone cement for treating DFU has the characteristics of accelerating wound healing and better reconstruction of local blood flow, which may be closely related to the fact that antibiotic bone cement promoted the local angiogenesis effectively in the wound through enhancing the expression of VEGFR2.

[Effects of the anterolateral thigh chimeric perforator flaps in repairing complex wounds of foot and ankle].

Objective: To investigate the effects of anterolateral thigh chimeric perforator flap in repairing complex wounds of foot and ankle. Methods: A retrospective observational study was conducted. From May 2018 to June 2022, 23 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University to repair complex wounds of foot and ankle with anterolateral thigh chimeric perforator flaps, including 15 males and 8 females, aged from 20 to 66 years. The wounds were all accompanied by bone exposure and defects, and were complicated with varying degrees of infection. All patients underwent debridement and continuous vacuum sealing drainage treatment for 1 week in stage Ⅰ, with the skin and soft tissue defect area after debridement being 10 cm×5 cm to 22 cm×7 cm. In stage Ⅱ, the anterolateral thigh chimeric perforator flap was used to cover the defective wound, of which the muscle flap was used to fill the deep invalid cavity of the ankle joint or cover bone and internal fixation exposures, and the skin flap was used to cover the superficial wound, with the area of the skin flap ranging from 11 cm×6 cm to 23 cm×8 cm, and the area of the muscle flap ranging from 4.0 cm×2.5 cm to 8.0 cm×5.0 cm. The survival of the flap was observed after operation. During follow-up, the color, texture, appearance, and complications of the flap were observed, the function of ankle joint and its range of dorsiflexion motion and plantar flexion motion were measured, and the scar hyperplasia and muscular hernia in donor area were observed. Results: Ecchymosis and epidermal necrosis occurred at the tip of the flap in 1 patient on 5 days after operation and healed after dressing change for 1 week; the other flaps of patients survived successfully. After 6 to 40 months of follow-up, the color, texture, and shape of flaps were good, but 1 patient was not satisfied with the shape of the flap because of flap swelling; the ankle joint movement was basically normal, the dorsiflexion motion was 15-30°, and the plantar flexion motion was 20-45°; the scar hyperplasia in the donor area of the flap was not obvious, and no muscular hernia occurred. Conclusions: The anterolateral thigh chimeric perforator flap can effectively fill the deep invalid cavity of ankle joint and cover the superficial wound at the same time, with minimal damage to the donor site. So it is an ideal flap for repairing the complex wounds of foot and ankle.