Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression. Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis. Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

The pathogenesis of Vogt-Koyanagi Harada disease (VKH) has not yet been fully defined. Current studies mainly suggest that VKH is actually an autoimmune disease, especially related to the immune response mediated by various signal transduction pathways involved in the function of T cells. In recent years, the influence of the balance imbalance of various T cell subsets in cellular immunity on the pathogenesis of VKH has been a hot research direction. Currently, T helper cell 17/T regulatory cells, balance is the focus of clinical research, meanwhile, new discoveries and potential clinical treatment schemes have been made for related cellular pathways, particularly the Janus kinase/signal transducers and activators of transcription pathway and NF-kappa B pathway. The exploration of B cells in the pathogenesis of VKH has also achieved initial results through the successful application of various targeted drugs. In the future, further screening and localization of genes or proteins that are abnormally regulated or expressed in VKH, for which early comprehensive and in-depth exploration will be helpful, thus improve the efficacy of clinical treatment programs and develop new therapeutic targets.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Mice ; Animals ; Humans ; Disease Models, Animal

Objective:To evaluate the curative effect of autogenous cartilage transplantation in the correction of nasal soft-tissue triangle deformities aided by 3D technology.Methods:From January 2016 to January 2018, 32 patients with nasal soft-tissue triangle deformities were collected, with 7 males and 25 females, aged from 18 to 32 years (mean 28.5±6.8 years). A part of the costal cartilage/nasal septum cartilage or auricular cartilage was cut as repair material, which was carved into strips, and used as nasal alar rim grafts to reconstruct the dome shape and correct the nasal soft triangle deformities. The costal cartilage or nasal septum cartilage was used to strengthen the support of the columella nasi and augmentation rhinoplasty was performed with prosthesis, and the fascia was placed on nose tip to relieve tension. The surgical results were evaluated by comparing the pre- and post-operative images; statistical analysis was conducted to compare the difference of alar cartilage angle along inside and outside implants before and after the fornix reconstruction, and the difference of maximum distance from the nostrils long shaft to the nose flange between pre- and post-operation, and so the effect of nasal soft triangular deformity correction was evaluated.Results:The alar cartilage angle of the 32 patients was (51.5±10.9)° before surgery, and decreased to (37.2±5.9)° after surgery; the difference was statistically significant ( P<0.05). The maximum distance from the nostrils long shaft to the nose flange was (3.3±0.6) mm before surgery, and it reduced to (1.9±0.7) mm after surgery; the difference was statistically significant ( P<0.05). The patients were followed up for 6 to 18 months, and the result showed that the curative effect was significant, with good appearance and natural feeling, and there were no serious complications, and the satisfactory rate was 87.5%. Conclusions:Autogenous cartilage is used to repair nasal soft-tissue triangle deformities aided by 3D technology; the nasal morphology is improved delicately, and the postoperative satisfaction of curative effect is high, which is an ideal surgical method.

Objective To investigate the effects of upadacitinib on the polarization and inflammation of BV2 microglia after oxygen glucose deprivation/recovery (OGD/R) and to explore its mechanism of action. Methods The experiment was divided into 3 groups: control group, OGD group and upadacitinib treatment group. After BV2 cells were treated with OGD/R, MTT was used to detect cell survival rate. Wound scratch assay was used to detect the cell migration ability. qPCR was used to detect mRNA levels of M1-type polarization markers (CD11b, CD32, iNOS) and M2-type polarization markers (Arg-1, IL-10, CD206) of BV2 cells. ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the culture medium. Western blot was used to detect the expression levels of JAK1/STAT6 pathway-related proteins. Results Upadacitinib increased the survival of BV2 cells after OGD/R (P<0.05), reduced the polarization of BV2 cells to M1 type (P<0.05). Upadacitinib significantly decreased the migration ability of BV2 cells induced by OGD/R (P<0.05), reduced the inflammatory factors secreted by BV2 cells induced by OGD/R: IL-1β, IL-6, TNF-α (P<0.05). Upadacitinib increased the survival rate of co-cultured PC12 cells (P<0.05). Upadacitinib significantly inhibited the expression levels of p-JAK1 and p-STAT6 proteins in BV2 cells activated by OGD/R induction (P<0.05). Conclusion Upadacitinib decreases polarization of BV2 induced by OGD/R to M1 type and reduces inflammation, which is related to JAK1/STAT6 pathway.

Objective:To explore the application feasibility of modified sentinel lymph node biopsy (SLNB) for acral malignant melanoma.Methods:The data of 60 patients with acral malignant melanoma in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2017 to January 2020 were retrospectively analyzed. According to the sentinel lymph node (SLN) detection method, they were divided into observation group (30 cases) and control group (30 cases). The observation group used contrast-enhanced ultrasound combined with subcutaneous injection of methylene blue around the wrist or ankle joint to detect SLN; the control group used peritumoral injection of methylene blue to detect SLN. The patients were regularly followed up to evaluate the postoperative effect. The detection number, detection rate, sensitivity, false negative rate and the size of SLN were compared between the two groups.Results:In the observation group, the detection rate of SLN was 100.0% (30/30), the sensitivity was 87.5% (7/8), and the false negative rate was 3.3% (1/30); in the control group, the detection rate of SLN was 83.3% (25/30), the sensitivity was 62.5% (5/8), and the false negative rate was 12.0% (3/25); the differences were statistically significant (all P < 0.05). The number of SLN detected in the observation group (3.5±1.2) was significantly more than that in the control group (2.0±1.1), and the difference was statistically significant ( t = 7.121, P < 0.05). The minimum long-axis diameter of SLN detected in the observation group was (5.4±2.2) mm (range, 1.5-12.3 mm), and that in the control group was (11.8±5.4) mm (range, 10.0-16.8 mm), the difference between the two groups was statistically significant ( t = 6.353, P < 0.05). Conclusion:The modified SLNB for acral malignant melanoma has a higher application value in the detection of acral SLN than the peritumoral injection method, and a higher accuracy rate can be obtained.

Objective:To investigate the efficacy and safety of partial resection or enhanced suture of retro-orbicularis oculi fat (ROOF) through double eyelid or subeyebrow incision to correct upper eyelid swelling and depression.Methods:From May 2017 to June 2018, 166 beauty seekers underwent the operation. Among them, 81 cases were corrected by double eyelid incision, 33 cases were corrected by double eyelid incision, 30 cases were corrected by subeyebrow incision and 22 cases were corrected by subeyelid incision.Results:The swelling and depression of the upper eyelid were improved and the patients were satisfied. Two of the patients developed hematoma after operation and all healed after debridement.Conclusions:Preorbital septum fat combined with ROOF partial excision or enhanced suture can effectively improve the upper eyelid swelling or depression, with high satisfaction, safety and less trauma, which can be an important supplement for upper eyelid plastic surgery.

Objective:To investigate the feasibility of mandibular angle osteotomy combined with high-density polyethylene (MEDPOR) prosthesis implantation for one-time lower facial contouring of the protuberance and related surgical precautions.Methods:A total of 18 patients who were treated in the oral and maxillofacial surgery of Yangzhou First People＇s Hospital from June 2010 to August 2016 were selected to complete the mandibular angle osteotomy combined with MEDPOR prosthesis implantation in the lower part of the prosthetic plane. The patients were followed up regularly and the effect of surgery was observed.Results:All 18 patients were operated successfully with an average time of 2 hours. The effect of operation was satisfactory. Except for one patient whose hematoma caused local bruise to subside completely in 2 weeks, all the others were discharged smoothly in one week after operation. After 2 months to 3 years of follow-up, the effect was satisfactory.Conclusions:Mandibular angle osteotomy combined with MEDPOR prosthesis is safe and effective.