Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Objective Reliability and validity of the Chinese version of disability attitude scales(DAS-CN)toward disabled persons were created and tested to provide an assessment instrument for measuring the attitude of medical staff toward disabled persons in China.Methods Authorised by the author of DAS in August 2020,based on BRISLIN translation model,the English version of DAS was translated into Chinese followed by back translation,cultural debugging and then put it into pre-experiment in September 2020.The reliability and validity of the finalised DAS-CN were further tested in a survey with 400 randomly selected medical staff in rehabilitation from 8 general hospitals in Jinzhou,Panjin,Yingkou and Fushun in Liaoning Province,China by using the convenience sampling method in March 2021.Results A total of 357 surveyees completed the survey.The localised DSA-CN was composed of 4 dimensions with a total of 20 items,including 4 items in clinical knowledge and skills,4 in clinical responsibility,8 in clinical behaviour and 4 in emotional response.The Cronbach α coefficient of the scales was 0.943,with the split-half reliability and test-retest reliability at 0.824 and 0.899,respectively.The Cronbach α coefficient of each dimension was 0.843～0.944,and the split half reliability was 0.854～0.904.The test-retest reliability ranged from 0.701 to 0.913.The KMO value of exploratory factor analysis was 0.921.The Bartrett spherical test value was 5534.981(P<0.01).The total explanatory rate of variation was 73.050%.Conclusion The Chinese version of Disability Attitude Scales(DSA-CN)has good reliability and validity.Therefore,DSA-CN can be used as an instrument in investigation of the current status about the attitudes towards the disabled persons among the medical staff in China.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Unilateral biportal endoscopic surgery, micro-endoscopic discectomy, micro-endoscopic laminoplasty, and Destandau mobile endoscopic discectomy have been described as four major techniques in the field of endoscopic spine surgeries. Compared with the coaxial endoscopy, the unilateral biportal endoscopic surgery is characterized by separated channels for observation and operation, making operative procedures more flexible, vision field wider, and requirements for surgical instruments less demanding. Although the anatomical basis of its surgical approach is similar to that of micro-endoscopic spine surgery, this technique can significantly reduce the injury to the paravertebral muscle and protect the stability of the surgical segment of the spine, leading to quick and wide applications in the clinical treatment of degenerative lumbar diseases with good clinical efficacy. The present article reviews this surgical technique from the aspects of technological development, anatomical basis, clinical application, complications, and prospects.

Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Objective:To investigate the pain status in diabetic foot ulcer (DFU) patients and analyze its influencing factors.Methods:A single-center cross-sectional survey research method was used. From May 2021 to February 2022, DFU patients who were admitted to the Fourth Medical Center of PLA General Hospital and met the inclusion criteria were selected and investigated. The scores of the heaviest pain, the least pain, the average pain, and the current pain in pain degree and the total score and the scores of influence on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest in pain-related effects and the total score of patients were evaluated by the brief pain inventory. A self-designed general data questionnaire was used to collect the data including patients' gender, age, education level, body mass index, self-care ability, diabetes course, wound Wagner grade, bacterial culture result of wound specimen, and the levels of glycated hemoglobin, albumin, prealbumin, hemoglobin, and leukocyte count. Patients were classified according to general data, and the total scores of pain degree and pain-related effects were counted. Data were statistically analyzed with Kruskal-Wallis test and Mann-Whitney U test. The indicators with statistically significant differences in univariate analysis were selected for generalized linear model analysis to screen the independent risk factors of pain severity and pain-related effects in DFU patients. Results:A total of 44 questionnaires were sent out, and 42 valid questionnaires were collected, with effective recovery of 95.45%. The scores of the heaviest pain, the least pain, the average pain, and the current pain in DFU patients were 5 (0, 10), 2 (0, 6), 3 (0, 8), and 2 (0, 8), respectively, and the total score of the pain severity was 11 (0, 24); the scores of pain-related effects on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest were 4 (0, 10), 4 (0, 10), 5 (0, 10), 5 (0, 10), 3 (0, 10), 4 (0, 10), and 4 (0, 10), respectively, and the total score of pain-related effects was 30 (0, 63). In 42 DFU patients, most patients were male, aged 39-87 (67±10) years, most patients had education level of junior high school, most patients had diabetes for more than 20 years, half of patients' wounds were Wagner grade 4, most patients had body mass index and leukocyte count within normal limits, most patients had partial dependence on self-care ability, the bacterial culture results of wound specimen in the vast majority of patients were positive, about half of the patients had abnormal level of albumin, and most patients had abnormal levels of glycosylated hemoglobin, prealbumin, and hemoglobin. Univariate analysis of the above general data showed that total scores of pain severity among patients with different hemoglobin levels and leukocyte counts were statistically significant different (with Z values of -2.05 and -2.55, respectively, P<0.05), and the total scores of pain-related effects on patients with different hemoglobin levels, leukocyte counts, and bacterial culture results of wound specimen were statistically significant different (with Z values of -2.66, -2.02, and -2.12, respectively, P<0.05). Generalized linear model analysis showed that leukocyte count was an independent risk factor for pain severity and pain-related effects in 42 DFU patients (with 95% confidence intervals of 0.28-11.87 and 5.67-36.99, respectively, standardized regression coefficient values of 6.17 and 21.33, respectively, both P values <0.05). The bacterial culture result of wound specimen was an independent risk factor for pain-related effects in 42 DFU patients (with 95% confidence interval of 2.92-39.09, standardized regression coefficient value of 21.00, P<0.05). Conclusions:DFU patients often suffer pain, and the bacterial culture results of wound specimen and leukocyte count are the main factors affecting the pain of DFU patients.

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.

To analyze the clinical data of 2 neonates with Langerhans cell histiocytosis (LCH). The rashes appeared in both cases shortly after birth.Case 1 had both rashes and neonatal sepsis, and no other tissues and organs were involved.After anti-infective treatment, the rashes gradually disappeared.Case 2 had secondary pneumonia, abnormal coagulation function and gastrointestinal bleeding.Both cases were positive for CD1a and S-100 by immunohistochemical staining of skin biopsy, and they were diagnosed as multi system-LCH.The early diagnosis of LCH is particularly important.The detection methods of skin or lymph node biopsy like immunohistochemistry, need to be performed as early as possible.Because the course of the disease is not clear, a close monitoring and follow-up are needed.

Objective:To explore the clinical strategies for preservation of the exposed implant in chronic wounds and wound repair.Methods:From January 2016 to January 2019, totally 8 patients (4 males and 4 females, aged 10 to 73 years) sustaining postoperative chronic wounds with exposed implants were admitted to the Fourth Medical Center of PLA General Hospital. There were 2 cases of abdominal patch exposure after abdominal trauma surgery, 2 cases of titanium plate exposure post craniocerebral surgery, 3 cases of internal fixator exposure post orthopedic surgery, and 1 case of cerebrospinal fluid drainage tube exposure after craniocerebral surgery. The wound exudate was collected for bacterial culture on admission. On the basis of glycemic control and correction of anemia and hypoproteinemia, thorough wound debridement was performed as soon as possible and the wound area after debridement ranged from 2.0 cm×0.5 cm to 6.0 cm×5.0 cm. The wounds of 4 patients were immediately closed after debridement, including 1 case by primary closure, 1 case by primary closure after local filling of platelet rich plasma gel, and 2 cases by local flap transplantation, with flap size of 10.0 cm×8.0 cm and 12.0 cm×8.0 cm, respectively. The donor sites of flaps were sutured directly and all the incisions were treated with continuous vacuum sealing drainage (VSD) after surgery. The other 4 patients were treated with continuous VSD after debridement to improve the wound bed. The wound of 1 case healed gradually, 1 case received direct wound suturing, and the wounds of 2 cases were repaired with thin split-thickness skin grafts from the thigh or the head. The results of bacterial culture of wound exudate on admission, wound healing post surgery, and follow-up were observed and recorded.Results:The bacterial culture of wound exudate on admission was positive in 6 patients, and 10 strains of bacteria were isolated with Staphylococcus epidermidis as the main pathogen. All the skin grafts or flaps of patients survived post surgery, with the incisions and wounds healed and all the implants preserved. After 1 to 3 years of follow-up, no recurrence of wound was found in any patient. Conclusions:The postoperative chronic wounds with exposed implants can be closed in primary stage by direct suturing or flap transplantation if it is clean enough on the basis of thorough debridement. The wounds with large defects or serious infection can be treated with continuous VSD firstly and then closed with direct suturing or skin grafting for delayed wound closure, thereby to reach the treatment goal of preserving the implants and repairing the wounds simultaneously.