Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.

Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.

Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate,posing a serious threat to human health.Sodium-glucose linked transporter 2(SGLT2)inhibitors are a new type of oral hypoglycemic drug.SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion,but also by improving islet β cell function,reducing inflammatory responses,and inhibiting oxidative stress.In addition,SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism;reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function.They can also improve blood lipids by increasing degradation of triacylglycerol;reduce blood uric acid by promoting uric acid excretion in kidney and intestine,and by reducing uric acid synthesis.This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

An ideal ionizing radiation biomarker should be able to quickly,conveniently and accurately assess the radiation dose received by individuals,and can predict the effect of radiation-induced damage.Radiation dose assessment based on gene or molecular expression profiles is a research focus in the field of radiation biodosimetry.Non-coding RNA and proteomics have the characteristic of high-throughput that allows for rapid and real-time detection,making them highly potential for radiation biodosimetry research.This paper summarizes the research progress of non-coding RNA and proteins as potential radiation biomarkers in recent years,and also reviews their influencing factors and application scenarios.

Objective To investigate the protective effect of ginsenoside Rg3 on lipopolysaccharide-induced galial-neuronal interaction injury model.Methods Primary microglia cells and HT-22 cell lines were cultured,and the cells were divided into the control group(CON),the 100 ng/mL LPS group(LPS),the control inflammation model group(CM),the ginsenoside Rg3 group,and the inflammation model plus ginsenoside Rg3 treatment group(CM+Rg3).Ginsenoside Rg3 was administered in the ginsenoside Rg3 group and the CM+Rg3 group at the doses of 2.5,5,10,and 20 μmol/L.Galial-neuronal interaction modeling was performed in the CM group and the CM+Rg3 group.The purity of the primary microglia cells was assessed by immunofluorescence,the viability of the HT-22 cells in each group was assessed by CCK-8,and changes in the levels of inflammatory cytokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor α(TNF-α),and IL-10,in the cell samples of each group were assessed with the ELISA kits.The level of cellular oxidative damage was measured with a ROS kit,and the expression of apoptosis-related proteins,including Bax and Bcl-2,was assessed by Western blot.The activity of Caspase-3 enzyme in each group was measured with a Caspase-3 enzyme activity kit.Results The purity of the microglia cultured reached over 95％and was suitable for subsequent experiments.After ginsenoside Rg3 stimulation at different doses,the survival rate of HT-22 was not much different from that of the CON group.The survival rate of neurons after 100 ng/mL LPS stimulation was 98％,indicating that Rg3 and LPS had no effect on the survival of neurons.Compared with that of the CON group,the survival rate of HT-22 cells in the CM group was significantly decreased(P＜0.01).Compared with the CM group,the CM+Rg3 group showed a significant increase in the viability of neurons(P＜0.0l),indicating that the glia-neuron interaction model was successfully constructed.When Rg3 dose was 10 μmol/L,the HT-22 cells in CM+Rg3 group showed the highest viability(P＜0.05).Hence,10 μmol/L Rg3 was selected for further experiments.After 100 ng/mL LPS stimulation,the concentrations of IL-1 β,IL-6,TNF-α,and IL-10 in HT-22 cells were not significantly different from those in the CON group.After 100 ng/mL LPS stimulation,the concentrations of IL-lβ and TNF-α in microglia were higher than those in the CON group(P＜0.05),but the concentrations of IL-1 β and TNF-α in the LPS+Rg3 group were lower than those in the LPS group(P＜0.05).The concentration of reactive oxygen species in the CM+Rg3 group was slightly higher than that in the CON group,and significantly lower than that in the CM group(P＜0.01).The expression of Bax in the CM+Rg3 group was higher than that in the CON group,and lower than that in the CM group.The expression of Bcl-2 was lower in the CON group,and higher than that in the CM group(P＜0.01).The Caspase-3 enzyme activity in the CM group was significantly higher than that in the CON group(P＜0.01).The Caspase-3 enzyme activity in the CM+Rg3 group was significantly lower than that in the CM group(P＜0.01).Conclusion Ginsenoside Rg3 may play a role in the alleviation of neuronal apoptosis by regulating glial cell damage,reducing the secretion of inflammatory factors,and inhibiting neuronal apoptosis.

Objective:To investigate the role of three-dimensional dose distribution-based deep learning model in predicting distant metastasis of head and neck cancer.Methods:Radiotherapy and clinical follow-up data of 237 patients with head and neck cancer undergoing intensity-modulated radiotherapy (IMRT) from 4 different institutions were collected. Among them, 131 patients from HGJ and CHUS institutions were used as the training set, 65 patients from CHUM institution as the validation set, and 41 patients from HMR institution as the test set. Three-dimensional dose distribution and GTV contours of 131 patients in the training set were input into the DM-DOSE model for training and then validated with validation set data. Finally, the independent test set data were used for evaluation. The evaluation content included the area under receiver operating characteristic curve (AUC), balanced accuracy, sensitivity, specificity, concordance index and Kaplan-Meier survival curve analysis.Results:In terms of prognostic prediction of distant metastasis of head and neck cancer, the DM-DOSE model based on three-dimensional dose distribution and GTV contours achieved the optimal prognostic prediction performance, with an AUC of 0.924, and could significantly distinguish patients with high and low risk of distant metastasis (log-rank test, P<0.001). Conclusion:Three-dimensional dose distribution has good predictive value for distant metastasis in head and neck cancer patients treated with IMRT, and the constructed prediction model can effectively predict distant metastasis.

Objective Based on the theory of"gut-brain",this study explored the effect of acupuncture on the gut microbiota and central inflammation in migraine model rats,in order to explore the mechanism of acupuncture in the treatment of migraine from the perspective of"gut-brain".Methods The migraine rat model was established by subcutaneous injection of nitroglycerin.They were randomly divided into a model group and an acupuncture group,with 6 rats in each group,and a control group with 6 rats for conventional binding and fixation.Before modeling and on the 1st,5th,and 9th days after modeling,each group used electronic VonFrey to measure the plantar mechanical pain threshold of rats.After the experiment,Elisa was used to detect the expression levels of inflammatory factors IL-6 and TNF-α in the central trigeminal spinal nucleus of the rats in each group.Three-generation Pacbio full-length microbial diversity sequencing was used to perform 16S full-length rDNA sequencing on each group of fecal samples to detect the operational taxonomic unit(OTU)clustering and its abundance,Alpha diversity index,Beta diversity index,species among the samples in each group.differences in abundance.Results In migraine model rats,plantar mechanical pain threshold was significantly decreased(P<0.01),central IL-6 and TNF-α contents were significantly increased(P<0.01),and the structure and abundance of gut microbiota were abnormal.change(P<0.01).Continuous acupuncture treatment can significantly increase the plantar mechanical pain threshold in migraine rats(P<0.01),regulate the diversity of gut microbiota in migraine rats,increase Lactobacillus murine,and reduce the abundance of Lactobacillus enterobacteriaceae.degree(P<0.05),and decreased the levels of IL-6 and TNF-α in the central nervous system of migraine model rats(P<0.01).Conclusion Acupuncture can exert the"gut-brain"anti-inflammatory and analgesic effect of acupuncture in the treatment of migraine by regulating the gut microbiota structure and the expression of central IL-6 and TNF-α inflammatory factors in migraine model rats.

Breast cancer is the most common cancer among women worldwide, and it seriously threatens women′s life and health. circular RNA (circRNA) play a key role in the development and drug resistance of various cancers, including breast cancer. circRNA is an endogenous RNA molecule with a single-stranded closed structure, which has unique biological characteristics and function, and is a current research hotspot. This article will review circRNA as potential biomarkers to predict breast cancer drug resistance and therapeutic targets.

Objective:To investigate the efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy on prostate cancer (PCa) detection in biopsy-na?ve patients.Methods:The clinical data of 121 biopsy-na?ve patients who underwent transperineal prostate biopsy in West China Hospital of Sichuan University from July 2018 to January 2020 were retrospectively analyzed. The average age was (64.7±9.1) years old. Pre-biopsy prostate-specific antigen (PSA) was (12.4±7.5)ng/ml, f/t PSA was 0.13±0.05. Prostate volume was (43.1±26.1) ml and PASD was (0.35±0.27) ng/ml 2. The prostate-imaging and data system (PI-RADS) score of MRI before biopsy was reported to be 3 for 29 patients (24.0%), 4 for 54 patients (44.6%) and 5 for 38 patients (31.8%). All 121 patients underwent 12-core systematic biopsy combined with a 3-core or 5-core MRI-targeted biopsy, of which 61 patients underwent 3-core targeted biopsy and 60 underwent 5-core targeted biopsy. There was no significant difference in the pre-biopsy clinical data between the two groups ( P>0.05). A 6-core systematic biopsy was redefined as the results of 6 cores among the 12-core systematic biopsy. We compared the detection rates among the single 12-core systematic biopsy, 6-core systematic biopsy, MRI-targeted biopsy (3-core or 5-core), and different systematic biopsy combing with targeted biopsy for any PCa and clinically significant PCa, and we also analyzed the cumulative cancer detection rates for MRI-targeted biopsy of different cores. Results:Of the 121 patients in this study, the biopsy results were negative for 43 patients (35.5%) and positive for 78 (64.5%). The detection rate of clinically significant PCa was 55.4% (67/121). The detection rate of the 6-core systematic biopsy combined with MRI-targeted biopsy was 62.0% (75/121) for PCa and 55.4% (67/121) for clinically significant PCa, which was of no difference compared with that for the 12-core systematic biopsy combined with MRI-targeted biopsy ( P>0.05), but the 6-core systematic biopsy combined with MRI-targeted biopsy avoided the overdiagnosis of 3 patients with Gleason score 3+ 3. The detection rate of PCa for MRI-targeted biopsy was 57.9% (70/121), including 42.1% (51/121) for the first core, 55.4% (67/121) for the first two cores, and 57.9% (70/121) for the first three cores. Compared with the single-core targeted biopsy for suspicious lesions, the first 2-core targeted biopsy ( OR=1.7, 95% CI 1.0-2.8) and 3-core targeted biopsy ( OR=1.9, 95% CI 1.1-3.1) can significantly increase the detection rate of PCa, while the fourth or fifth core of targeted biopsy can not increase the detection rate additionally (60%, 36/60). Conclusion:For patients with suspected PCa, the prostate biopsy strategy combing 6-core systematic and 3-core MRI-targeted biopsy performs no inferior than the current 12-core systematic biopsy combined with MRI-targeted biopsy.

Objective:To compare the clinical effects of 4 kinds of neurocutaneous perforator flap with vascular anastomosis for repair of hand and foot wounds.Methods:From January, 2005 to September, 2019, 112 patients with hand and foot wounds were treated, there were 78 cases of fingers, 11 cases of first web, 5 cases of palm, 6 cases of hand and 12 cases of foot. The defect area was 2.0 cm×1.5 cm-21.0 cm×12.0 cm. All 112 cases were repaired by neurocutaneous perforator flaps anastomosed with blood vessels. Types of flap were applied: Radial collateral artery perforator flap (with posterior cutaneous nerve of forearm) in 30 cases. The flap area was 5.0 cm×2.0 cm-13.0 cm×6.0 cm. Superficial peroneal artery flap (without superficial peroneal nerve) anastomosed with blood vessels in 15 cases. The flap area was 2.5 cm×2.0 cm-9.0 cm×6.0 cm. Lateral superficial sural artery perforator flap (with superior sural cutaneous nerve) in 26 cases. The flap area was 2.5 cm×1.8 cm-7.0 cm×5.0 cm. Peroneal artery perforator flap (with middle and lower sural nerve) in 41 cases. The flap was harvested with area of 2.5 cm×1.8 cm-23.0 cm ×14.0 cm to repair the wounds of feet, back of hands, first web, palm and fingers. CTA images were observed in 40 clinical patients, and the occurrence rate of radial collateral artery, superficial peroneal artery, superficial lateral sural artery, and peroneal artery were measured. Anastomosis cutaneous nerve in 97 cases, and no cutaneous nerve anastomosis 15 cases (superficial peroneal artery flap).Results:The peroneal artery perforator flap (41 cases) and radial collateral artery perforator flap (30 cases) were harvested. The incidence of perforator vessels was both 100%, and incidence of superficial sural artery was 80.8% (21/26 cases). In the other 19.2% (5/26 cases), the superficial medial sural artery was replaced by too thin vessels. The utilization rate of superficial peroneal artery was 60.0% (9/15 cases), the other 40.0% (6/15 cases) were converted to peroneal artery perforator flap. All flaps survived except 1 case of superficial perforator flap of lateral sural artery, which underwent necrosis at the distal end and healed after dressing change. One hundred and one cases were followed-up, including 90 cases for repairing soft tissue defects in hands and 11 cases in feet. The followed-up time ranged from 12 to 120 months, with an average of 36.6 months. There were 40 cases with excellent function, 45 cases with good function and 5 cases with fair function. There were 78 cases of cutaneous nerve anastomosis of hand flap, and the sensory function was above S 3 level. There were 12 cases without anastomosis of cutaneous nerve of hand flap, and the sensory function reached S 3 level in 3 cases and S 2 level in 9 cases. In 11 cases, the cutaneous nerve was anastomosed to repair the soft tissue defect of the foot, and the sensory function was above S 3 level. The radial collateral artery perforator flaps were relatively bulky and needed to be treated by fat removal. The other 3 kinds of three flaps were not bulky. Conclusion:The perforating vessels of peroneal artery and radial accessory artery have larger diameter and easy to harvest. The superficial peroneal artery and the lateral superficial sural artery are relatively small in caliber, especially the superficial peroneal artery. Among the 4 kinds of cutaneous nerve nutrient vascular flaps, the radial accessory artery perforator flap was the most bloated. Sensory nerve innervation flaps were found in the upper segment of lateral sural cutaneous nerve, posterior forearm cutaneous nerve and middle and lower segment of sural nerve. The superficial peroneal artery perforator flap was accompanied by superficial peroneal nerve that did not send cutaneous branches into the flap. The upper segment of superficial peroneal nerve was only a passing nerve.