Hui Xu’s research while affiliated with Wenzhou Medical University and other places

After spinal cord injury (SCI), microglia polarization plays an important role in spinal cord recovery and axon regeneration. In this study, we conducted mRNA microarrays to identify genes associated with different microglial phenotypes. The results showed a correlation between microglial polarization and the PI3K/AKT signaling pathway, a key regulator of inflammatory responses. In addition, we found that Pectolinarin (PTR) could effectively inhibit lipopolysaccharide (LPS)-induced M1 polarization of microglia and facilitate their transition to the M2 phenotype by directly suppressing the PI3K/AKT signaling pathway. In our established animal model of SCI, it was confirmed that PTR treatment induced microglial polarization towards the M2 phenotype, resulting in reduced fibrous scar formation, enhanced myelin reconstitution, and improved axonal regeneration. In conclusion, targeting the PI3K/AKT signaling pathway with PTR presents a promising new direction for SCI treatment. Graphical Abstract

Background Primary malignant melanoma (MM) of skin threatens health, especially in the older population, causing a significant risk of early death. The purpose of this study was to establish a diagnostic nomogram to predict the early mortality risk in older patients with primary skin MM and to determine the independent risk factors of cancer-specific early death in such patients. Methods The Surveillance, Epidemiology and End Results (SEER) database provided the clinical and pathological characteristics of older patients with primary skin MM from 2000 to 2019. Initially, a 7:3 random assignment was used to place the recruited patients into training and validation cohorts. Then, the independent risk variables of cancer-specific early death in those individuals were determined using univariate and multivariate logistic regression analysis. Those patients’ diagnostic nomograms were constructed using the acquired independent risk variables. Ultimately, the performance of the newly created diagnostic nomogram was verified using calibration curves, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Results In this study, 2,615 patients in total were included. Age, histology, liver metastasis, tumor stage, surgery, therapy, and radiation were found to be independent risk factors following statistical analysis, with a special emphasis on early death in older patients with primary skin MM. A diagnostic nomogram for the cancer-specific early death risk was created and validated based on these variables. High agreement was reported between the expected and actual probabilities in the calibration curves. Area under the curves (AUC) of the novel created diagnostic nomogram was greater than that of each independent risk factor, with AUCs for the training and validation cohorts being 0.966 and 0.971, respectively. The nomogram had a high value for its applicability in clinical settings, according to DCA. Conclusion In older patients with primary skin MM, the current study created a diagnostic nomogram to predict the probability of cancer-specific early death. Because of the nomograms’ good performance, physicians will be better able to identify older patients who are at a high risk of early death and treat them individually to increase their survival benefit.

Melanocytic nevi (MN), which are the most prevalent benign skin tumors, can be classified into three subtypes based on the depth of the nevus cell nests: junctional, compound, and intradermal nevi. Among these subtypes, intradermal nevi pose a lower risk of malignancy, whereas junctional nevi carry a higher risk of malignancy. To facilitate early stage diagnosis, mitigate unnecessary biopsies, and reduce medical costs, this paper presents the first study on the classification of benign melanocytic nevi. We propose an algorithm that utilizes depth-relevant, channel-specific, and channel-shared information from dermoscopy images. This approach draws inspiration from the physical principles underlying dermoscopy imaging and the physiological essence of nevi. We employed CNN and transformer blocks to capture local and long-range contextual information. In addition, our physiology-inspired module focuses on learning depth-related features from the color channels. To assess the performance of our proposed method, we curated a dataset of dermoscopic images of MN and compared it with two human experts as well as classic CNN and Transformer baseline models. Our results showed that the proposed automated method achieved an average accuracy of 70.23%, surpassing the best-performing baseline by 3.6%, and outperforming human experts by nearly 20%. Furthermore, we conducted an ablation study to confirm the effectiveness of our algorithm and to analyze its clinical significance.

The loss of epidermal melanocytes is a distinguishing feature of vitiligo (VIT), a prevalent and long-lasting skin ailment. While various hypotheses exist to explain the cause of VIT, the precise mechanisms leading to this disease remain unclear. Zinc finger MIZ-type containing 1 (ZMIZ1) has a strong link with the development and occurrence of VIT. However, the exact role of ZMIZ1 and its underlying mechanisms in VIT are not well understood. Our study aims to illustrate that targeting ZMIZ1 is an effective therapeutic and prophylactic strategy for treating VIT. We obtained the RNA expression profile of VIT samples using RNA-seq and determined the locations and expression of ZMIZ1 in these samples via immunochemistry. Glucose uptake was analyzed through immunofluorescence and glucose uptake assay. We evaluated mRNA levels using qPCR and used plasmids transfection to knock down ZMIZ1 in PIG1 and PIG3V cell lines. The activation of the mTOR/AKT/GSK-3β signalling pathway was assessed using Western blotting analysis. We found that ZMIZ1 expression was decreased in VIT samples. Decreased ZMIZ1 expression inhibits the proliferation, migration, and invasion of melanocytes in vitro. Moreover, we revealed that decreased ZMIZ1 could also inhibit the glucose uptake of melanocytes in vitro. Decreased ZMIZ1 expression inhibits the activation of the mTOR/AKT/GSK-3β pathway and the expression of melanin synthesis-related proteins in melanocytes. Finally, we demonstrated that decreased ZMIZ1 may inhibit the cell viability of melanocytes and the synthesis of melanin by mTOR/AKT/GSK-3β-mediated oxidative stress in vitro. In conclusion, our study suggests that decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating the mTOR/AKT/GSK-3β-mediated glucose uptake in vitro, making ZMIZ1 an attractive therapeutic target for the treatment of VIT.

Background: Acquired digital fibrokeratoma (ADFK) is an uncommon benign fibro-epithelioma, which is rarely reported in China. Aims: To analysis the clinical features of ADFK in Chinese people from current cases. Methods: From December 2019 to October 2021, there were 21 patients diagnosed with ADFK, we made a retrospective analysis on the clinical features of skin lesions in them. To summarize the clinical morphology, location, and surgical follow-up of ADFK. Results: We concluded that ADFK is more common in females than males on the hands (7:3), while the male-to-female ratio is largely the same in feet (6:5). It occurs more frequently on the third finger (60%) and first toe (45.5%). As to clinical morphology, it is typically rod-shaped (52.4%), followed by dome-shaped (42.8%) and wart-shaped (4.8%). It is typically dome-shaped on the hands (80%) and rod-shaped on the feet (81.8%). In terms of location on the fingers (toes), such skin lesions are most common at the proximal nail fold (52.4%), which can also occur at the nail matrix (14.3%), periungual area (23.8%), and subungual area (9.5%). Nevertheless, this ratio also varies on the hands and feet. All patients got surgical excision of the skin lesion, who were followed up for 6-12 months, without recurrence. Conclusions: Most ADFKs are associated with trauma, whose clinical features are related to location and gender. ADFKs on the hands are different from those on the feet regarding clinical morphology and location on fingers (toes), and surgery is effective in treating this condition.

Background: Acne vulgaris (AV) is a common inflammatory skin disease. Although various mechanisms have been indicated in the etiopathogenesis of AV, the exact pathophysiology remains unknown. Various lasers have been used to treat AV; however, the serum level changes of inflammatory cytokines after laser therapy have not been elucidated. We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595- and 1 064-nm dual-wavelength laser. Methods: In total, 18 patients (9 male and 9 female) between 16 and 35 years of age with moderate to severe AV were evaluated in the study. Disease severity was classified according to the Pillsbury grading system of acne. Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment. A 3 mL blood sample was drawn from every subject each time, and serum levels of inflammatory cytokines such as interleukin (IL)-6, IL-8, and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment. Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation. Results: Inflammation was significantly reduced on both the treated and untreated sides, and symptoms of AV lesions were alleviated. All patients showed a significant increase in serum IL-22 levels after the first laser therapy, with no significant difference in serum IL-6 and IL-8 levels. After the second laser therapy, serum IL-6, IL-8, and IL-22 levels were significantly decreased. No significant side effects such as bruising, edema, hyperpigmentation, hypopigmentation, or scarring were reported. Conclusion: Half-face treatment with 595- and 1 064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission, which was associated with a gradual decrease in IL-6, IL-8, and IL-22 levels after half-face topical treatment. This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites. This laser treatment is effective, economical, and painless.

Injury to the meniscus is a common occurrence in the knee joint and its management remains a significant challenge in the clinic. Appropriate cell source is essential to cell-based tissue regeneration and cell therapy. Herein, three commonly used cell sources, namely, bone marrow mesenchymal stem cell (BMSC), adipose-derived stem cell (ADSC), and articular chondrocyte, were comparatively evaluated to determine their potential for engineered meniscus tissue in the absence of growth factor stimulus. Cells were seeded on electrospun nanofiber yarn scaffolds that share similar aligned fibrous configurations with native meniscus tissue for constructing meniscus tissue in vitro. Our results show that cells proliferated robustly along nanofiber yarns to form organized cell-scaffold constructs, which recapitulate the typical circumferential fiber bundles of native meniscus. Chondrocytes exhibited different proliferative characteristics and formed engineered tissues with distinct biochemical and biomechanical properties compared to BMSC and ADSC. Chondrocytes maintained good chondrogenesis gene expression profiles and produced significantly increased chondrogenic matrix and form mature cartilage-like tissue as revealed by typical cartilage lacunae. In contrast, stem cells underwent predominately fibroblastic differentiation and generated greater collagen, which contributes to improved tensile strengths of cell-scaffold constructs in comparison to the chondrocyte. ADSC showed greater proliferative activity and increased collagen production than BMSC. These findings indicate that chondrocytes are superior to stem cells for constructing chondrogenic tissues while the latter is feasible to form fibroblastic tissue. Combination of chondrocytes and stem cells might be a possible solution to construct fibrocartilage tissue and meniscus repair and regeneration.

Background: Surgery in elder patients with intermural fibroids delays pregnancy, and GnRH-a can shrink uterine fibroids to a certain extent; therefore, for geriatric patients with fibroids, determining whether GnRH-a pretreatment before frozen-thawed embryo transfer (FET) can improve its success rate remains to be studied. We conducted this study to research whether GnRH-a pretreatment before hormone replacement treatment (HRT) could optimize the reproductive outcomes compared with others preparations in geriatric patients with intramural fibroids. Methods: According to the endometrial preparation, patients were divided into a GnRH-a-HRT group, a HRT group and a natural cycle (NC) group. The live birth rate (LBR) was the first outcome, and the clinical pregnancy outcome (CPR), the miscarriage rate, the first trimester abortion rate and the ectopic pregnancy rate were the secondary outcomes. Results: A total of 769 patients (aged 35 years or older) were included in this study. No significant difference was observed in the live birth rate (25.3% vs. 17.4% vs. 23.5%, p = 0.200) and the clinical pregnancy rate (46.3% vs. 46.1% vs. 55.4%, p = 0.052) among the three endometrial preparation regimens. Conclusion: In this study, for the geriatric patient with the intramural myoma, the pretreatment with GnRH-a did not show any advantage over the NC and HRT preparation groups before the FET, and the LBR was not significantly increased.

Background: Atrophic acne scars (AAS) impact the aesthetic appearance, inducing social and psychological problems. Effective and safe therapy for AAS is urgently needed now. Microneedling fractional radiofrequency (MFRF) has emerged as a minimal invasive alteration for treating AAS lately, while the existing data on Chinese population was few. Aims: We aimed to explore the effectivity and safety of MFRF in Chinese patients with facial AAS and analyze the response of different subtypes to MFRF treatment. Methods: We conducted a retrospective analysis using data from medical records and clinical photographs of 40 Chinese patients with AAS with Fitzpatrick skin type III-IV, all of them had received 3 MFRF treatments with 1-month intervals and were followed up 3 months after the last treatment. The clinical severity was assessed throughéchelle d'évaluation clinique des cicatrices d'acné (ECCA) score at each visit. Clinical photographs were taken by VISIA. Patients were asked to evaluate their satisfaction of the treatment using a 5-point Liker scale at the last visit. Results: ECCA score decreased more than a half at the last visit based on the baseline. Among the three types of AAS, the M-shaped scars respond most quickly to MFRF and the U-shaped scars improved the most after 3 months follow-up. A significant improvement was seen in clinical appearance, parallel to the change of ECCA, indicating the remarkable improvement of AAS after the MFRF treatment. Concomitant active acne was controlled along with the improvement of AAS. Statistics from VISIA showed excellent improvement in pores and texture as well. Side effects including pain and erythema were transient and mild. The number of MFRF treatment sessions was positively associated with the degree of improvement. Of the total 39 patients who had given a score of satisfaction, more than 89% (35 patients) were very satisfied or satisfied with the outcome. Conclusions: To sum up, our study reveals that MFRF provides high efficiency in treating Chinese AAS patients with high satisfaction and low risk of adverse effects. M-shaped scars are the most sensitive type to the treatment but the U-shaped scars improve most at the last visit. The simultaneous minimization of pores and improvement of skin texture imply the increased collagen stimulated by MFRF. Regular MFRF should be considered a good choice in treating AAS.

Purpose As the human body’s largest organ exposed to the external environment, the skin suffers from internal and external aging factors, leading to wrinkles, loss of elasticity, sagging, and rough appearance. However, little is known of the characteristics of skin aging of different body parts in Chinese women. Here, we study the signs of extrinsic skin aging in different body parts to identify the knowledge map of manifestations of aging in Chinese women. Patients and Methods Wrinkle and texture phenotypes and collagen samples from the face, neck, hands, and arms of 326 Chinese women were collected. The correlations between phenotypes and ages and the differences in phenotypes by age were evaluated. Results The wrinkle and texture phenotypes around the eyes and mouth and of the hands were strongly correlated with age. Ages 32 and 58 showed the largest number of differentially changed aging phenotypes. The number of aging phenotypes increased sharply between the ages of 24 and 30, suggesting that the skin was undergoing rapid aging. Eye aging was the most rapidly changing phenotype between 19 and 30 years old. Wrinkles at the corner of the eyes showed a significant difference in the older group, suggesting an early onset and long-term effects. Conclusion This is the first study to be performed on the characteristics of skin aging among Chinese women that takes account of multiple areas of the body. It was found that 24 years old was the time point at which the skin begins to age in Chinese women. This provides important clues for aging-related research and personalized skin care.