[Objective]To explore the occurrence of gasdermin D(GSDMD)-mediated pyroptosis and its effect on cell proliferation,migration and tubular formation abilities of synovial vascular endothelial cells(VEC)in rheumatoid arthritis(RA).[Methods]Synovium tissues from knee joints of 22 RA patients and 18 orthopaedic arthropathies(Orth.A)patients were collected.The level of activated GSDMD-NT segment in synovium was detected by Western blot.The clinical characteristics of RA patients were compared between high and low synovial GSDMD-NT groups.The cell localization of GSDMD in RA synovium was detected by immunofluorescence staining.RA synovial fluid was added to the culture of human umbilical vein endothelial cells(HUVEC)in vitro,and the level of apoptosis and expression of pyroptosis pathway proteins were detected.The effects of GSDMD on apoptosis,proliferation,migration and tubule formation of HUVEC cells were analyzed.[Results]GSDMD expression in RA synovium was significantly higher than that in Orth.A,and more severe joint destruction and higher microvascular count score were found in RA patients with high GSDMD-NT expression.Synovial VEC had positive expression of GSDMD.Stimulation with RA synovial fluid could induce GSDMD-mediated pyroptosis in HUVEC,increased the secretion of vascular endothelial growth factor(VEGF)and their abilities of proliferation,migration and tubule formation.Knockdown of GSDMD could reverse the above effects.[Conclusion]GSDMD-mediated pyroptosis of partial synovial VEC aggravates RA joint destruction through VEGF secretion that promotes proliferation,migration and angiogenesis of the remaining VEC,which may be a new target to block neovascularization and inhibit joint destruction in RA.

To promote the construction of a wound repair and regeneration system with Chinese characteristics, it is necessary to follow the principle of combining traditional Chinese and Western medicine, and integrate theory, clinical practice, and teaching. Traditional Chinese medicine emphasizes a holistic concept and the principle of dialectical treatment, while Western medicine focuses on etiological analysis and local treatment. The combination of Chinese and Western medicine can complement each other's advantages and improve treatment effectiveness. The key technological innovations in repairing and regenerating systems cover areas such as drug therapy, physical therapy, and the application of biomaterials. This article discusses the development potential and challenges of combining traditional Chinese and Western medicine in the field of wound repair and regeneration, providing new ideas and methods for the development of wound repair and regeneration. It is expected to bring better medical services and treatment effects to patients undergoing repair and regeneration.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

The increasing prevalence of the aging population, and inadequate and uneven distribution of medical resources, have led to a growing demand for telemedicine services. Gait disturbance is a primary symptom of neurological disorders such as Parkinson's disease (PD). This study proposed a novel approach for the quantitative assessment and analysis of gait disturbance from two-dimensional (2D) videos captured using smartphones. The approach used a convolutional pose machine to extract human body joints and a gait phase segmentation algorithm based on node motion characteristics to identify the gait phase. Moreover, it extracted features of the upper and lower limbs. A height ratio-based spatial feature extraction method was proposed that effectively captures spatial information. The proposed method underwent validation via error analysis, correction compensation, and accuracy verification using the motion capture system. Specifically, the proposed method achieved an extracted step length error of less than 3 cm. The proposed method underwent clinical validation, recruiting 64 patients with Parkinson's disease and 46 healthy controls of the same age group. Various gait indicators were statistically analyzed using three classic classification methods, with the random forest method achieving a classification accuracy of 91%. This method provides an objective, convenient, and intelligent solution for telemedicine focused on movement disorders in neurological diseases.
Humans ; Aged ; Parkinson Disease/diagnosis* ; Aging ; Algorithms ; Gait ; Lower Extremity

Objective:To study the antibacterial properties and in vivo and vitro biocompatibility of Cu-Fe-Zn alloy microfilament dressings, and to evaluate their wound healing promoting effect through clinical application.Methods:We evaluated the comprehensive antibacterial performance of dressings in vitro using plate counting method; After co culturing the extract of Cu-Fe-Zn alloy microfilament dressings with epidermal cells (HaCaT) and fibroblasts (NIH-3T3), their in-vitro biocompatibility was determined through the cell counting kit-8 (CCK-8) test; Further, Cu-Fe-Zn alloy microfilament dressing was applied to the wound surface of diabetes mice to test the biocompatibility of the material in vivo; Through a prospective randomized controlled trial, 50 burn and trauma patients admitted to the Burn and Plastic Surgery Department of the Third Xiangya Hospital of Central South University were selected and divided into an observation group of 25 patients and a control group of 25 patients. The observation group was treated with Cu-Fe-Zn alloy microfilament dressing, and the control group was treated with silver nanoparticle antibacterial dressing. The wound healing time and wound treatment effect of the two groups were compared.Results:The Cu 2+ release concentration of Cu-Fe-Zn alloy microfilament dressings detected by inductively coupled plasma-mass spectrometry (ICP-MS) was 1.3 μ g/ml, which had the effect of promoting the proliferation of HaCaT and NIH-3T3 cells (all P<0.05). The antibacterial rate of Cu-Fe-Zn alloy microfilament dressing against pseudomonas aeruginosa, escherichia coli and staphylococcus aureus reached 100%. The wound healing rate [(87.39±1.83)%] of diabetes mice treated with Cu-Fe-Zn alloy microfilament dressing was significantly higher than that of the control group [(58.66±3.54)%, P<0.05]. The inflammatory response of the wound tissue was relatively mild and the wound margin matrix was intact. The wound healing time of 25 patients treated with Cu-Fe-Zn alloy microfilament dressing [(23.52±10.02)d] was shorter than that of the control group [(40.84±21.22)d] ( t=17.159, P<0.001), and the overall treatment response rate of patients (96%) was significantly higher than that of the control group patients (64%) (χ 2=8.472, P=0.015). Conclusions:Cu-Fe-Zn alloy microfilament dressings have good antibacterial properties and biocompatibility, and have significant therapeutic effects on promoting wound healing. They not only effectively promote wound healing but also exert anti infection effects, and are expected to be a new type of wound repair dressing.

Objective:To investigate the prevalence of hypertension and its associated factors in rheumatoid arthritis (RA) patients.Methods:Consecutive Chinese patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demo-graphic data and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment, comorbidities and previous medications. Logistic regression analysis was used to evaluate the related factors of hypertension in RA patients.Results:There were 674 RA patients recruited with 82.3%(555/674) female and mean age (50±13) years. The prevalence rate of hypertension was 32.9% (222/674), followed by dyslipidemia (9.9%, n=67), type 2 diabetes (8.8%, n=59), hyperuricemia (8.5%, n=43), fatty liver disease (8.0%, n=54), cardiovascular disease (6.2%, n=42) and chronic kidney disease (3.3%, n=22). Compared with those without hypertension, RA patients with hypertension had advanced age with longstanding disease duration, higher disease activity indicators, worse joint destruction, and higher proportions of comorbidities. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia [ OR=1.977, 95% CI(1.002, 3.900)], dyslipidemia [ OR=1.903, 95% CI(1.102, 3.288)] and fatty liver disease [ OR=2.335, 95% CI(1.278, 4.265)] were risk factors of hypertension after adjustment for age and gender. Conclusion:Hyperten-sion is the most common comorbidity in RA patients which is associated with comor-bidities including hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hyperten-sion and other cardiovascular disease related comorbidities in RA patients should be emphasized.

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Wound repair is a fundamental task that the whole field of the Burn and Plastic surgery pays urgent attention to and longs for a breakthrough. In this column, wound repair balance laws theory is expounded and we are expecting people in the field gradually began to value the use of balance law. Guided by the law of balance principle, people are required to conduct scientific research, improve clinical technique and develop new materials. The theory is designed to improve the level of scientific research and clinical diagnosis, and will set up a new milestone in the field of wound repair.

Objective:To investigate the safety and efficacy of venetoclax with low-dose cytarabine (LDAC) in Chinese patients with acute myeloid leukemia (AML) who are unable to tolerate intensive induction chemotherapy.Methods:Adults ≥ 18 years with newly diagnosed AML who were ineligible for intensive chemotherapy were enrolled in this international, randomized, double-blind, placebo-controlled trial. Globally, patients ( n=211) were randomized 2∶1 to either venetoclax with LDAC or placebo with LDAC in 28-d cycles, with LDAC on days 1-10. The primary endpoint was OS; the secondary endpoints included response rates, event-free survival, and adverse events. Results:A total of 15 Chinese patients were enrolled (venetoclax arm, n=9; placebo arm, n=6) . The median age was 72 years (range, 61-86) . For the primary analysis, the venetoclax arm provided a 38% reduction in death risk compared with the placebo[hazard ratio ( HR) , 0.62 (95% CI 0.12-3.07) ]. An unplanned analysis with an additional 6 months of follow-up demonstrated a median OS of 9.0 months for venetoclax compared with 4.1 months for placebo. The complete remission (CR) rates with CR with incomplete blood count recovery (CRi) were 3/9 (33%) and 0/6 (0%) , respectively. The most common non-hematologic adverse effects (venetoclax vs placebo) were hypokalemia[5/9 (56%) vs 4/6 (67%) ], vomiting[4/9 (44%) vs 3/6 (50%) ], constipation[2/9 (22%) vs 4/6 (67%) ], and hypoalbuminemia[1/9 (11%) vs 4/6 (67%) ]. Conclusion:Venetoclax with LDAC demonstrated meaningful efficacy and a manageable safety profile in Chinese patients consistent with the observations from the global VIALE-C population, making it an important treatment option for patients with newly diagnosed AML who are otherwise ineligible for intensive chemotherapy.