Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

ObjectiveTo explore the possible mechanism of Tongfeng Decoction （痛风汤） for preventing and treating acute gouty arthritis. MethodsSixty Wistar male rats were divided into normal group， model group， colchicine group and low-， medium- and high-dose Tongfeng Decoction groups according to the random number table， 10 rats in each group. Tongfeng Decoction of 11.34， 22.68 and 45.36 g/kg were given by gavage to low-， medium- and high-dose Tongfeng Decoction groups， colchicine 3.15×10^-4 g/（kg·d） to the colchicine group， and normal saline 10 ml/（kg·d） to the normal group and model group respectively for 7 consecutive days. After 1 hour of gavage on day 5， rats in all groups except the normal group were modelled as acute gouty arthritis in the ankle joint of the right hind limb with the modified Coderre's method； rats in the normal group were injected with 0.2 ml of normal saline at the same location. The swelling degree of the ankle joint was measured before modelling and after 6 h， 12 h， 24 h and 48 h of modelling， respectively. HE staining was used to observe the histopathological and morphological changes in the synovial tissue of the ankle joint； immunoblotting and RT-qPCR were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， cysteine aspartate protease 1 （Caspase-1）， and interleukin 1β （IL-1β） protein and mRNA expression levels in ankle synovial tissues， respectively； immunohistochemistry was used to detect the positive expression of Caspase-1 and IL-1β in ankle synovial tissues； ELISA was used to detect the tumour necrosis factor alpha （TNF-α）， IL-1β， and interleukin in serum； immunofluorescence staining was used to observe the formation of neutrophil extracellular traps （NETs） in the synovial tissues of the ankle joints. ResultsCompared with the normal group， rats in the model group showed elevated joint swelling at all time points， significantly increased inflammatory cell infiltration and the number of synovial cell layers in the synovial tissues of the ankle joints， elevated NLRP3， Caspase-1， ASC and IL-1β protein and mRNA expression， elevated positive expression of Caspase-1 and IL-1β， increased formation of NETs， and elevation of TNF-α， IL-6， and IL-1β in serum （P＜0.05）. Compared with the model group， there was an improvement in synovial cell proliferation and inflammatory cell infiltration of the ankle joint in the colchicine group， high- and medium-dose Tongfeng Decoction groups. In the colchicine group and the high-， medium- and low-dose Tongfeng Decoction groups， the degree of joint swelling， positive expression of Caspase-1， IL-1β and formation of NETs in the synovial tissue of the ankle joint， and TNF-α， IL-6 and IL-1β in serum reduced 24 h and 48 h after modelling； in colchicine group and high-dose Tongfeng Decoction group， NLRP3， ASC， Caspase-1， IL-1β protein and mRNA expression in the synovial tissues of ankle joints all reduced （P＜0.05）. The colchicine group and high-dose Tongfeng Decoction group were superior to the low-dose Tongfeng Decoction group in reducing ASC， Caspase-1， IL-1β protein and mRNA expression in the ankle synovial tissues， the positive expression of Caspase-1， as well as TNF-α， IL-6， and IL-1β level in serum （P＜0.05）. ConclusionTongfeng Decoction showed effectiveness for the prevention and treatment of acute gouty arthritis， and its mechanism may be related to the inhibition of the assembly and activation of NLRP3 inflammatory vesicles in ankle synovial tissues， the inhibition of the release of inflammatory factors， and the formation of NETs.

Objective:To explore the learning experience of medical students in digital storytelling teaching,providing a theoretical basis for the practice and research of digital storytelling teaching.Methods:Qualitative research and mixed-method research containing qualitative studies on medical students'experiences in digital storytelling teaching were retrieved from domestic and foreign databases,with a retrieval time limit from database establishment to January 2024.The quality evaluation criteria for qualitative research from JBI Evidence-Based Healthcare Center were used to evaluate the quality of the included literature,and the meta-integration method was used to systematically integrate and analyze the results.Results:A total of 12 articles were included,44 research results were extracted,and 11 new categories were summarized and integrated into 3 integration results,including medical students benefit greatly from digital storytelling teaching;the unique advantages of digital storytelling as an emerging teaching tool;and the obstacles of digital storytelling in education.Conclusion:Medical students hold a positive attitude towards the teaching mode of digital storytelling and have gained a good learning experience from it.However,there are shortcomings such as the uneven quality of digital storytelling resources,and some medical students'unsuitability for the learning mode of digital storytelling.Further research is needed on ethical issues arising from the teaching mode of digital storytelling.

Objective To conduct a systematic review of relevant literature to understand the current status and influencing factors of telehealth readiness of clinical medical staff.Methods The Chinese and English databases of CNKI,Wanfang database,VIP,SinoMed,Pubmed,Embase,Cochrane Library,CINAHL,Web of Science were searched by computer.The Chinese and English literatures on the current status and influencing factors of remote health care readiness among medical staff personnel were collected.The search time was from the establishment of the database to July 12th,2023,and the literature was screened and evaluated.After data extraction and integration of the literature,descriptive analysis is conducted.Results 18 articles were ultimately included,involving 12 298 medical staff members.Research shows that the readiness of clinical medical staff for telehealth is currently at a moderate level and not optimistic.The relevant influencing factors are:medical staff factors,including general demography factors,willingness of medical care services,innovative self-efficacy,understanding and participation of telehealth care mode,and electronic information ability;organizational factors:including telemedicare policies,telemedicare training,sufficient human resource working environment and atmosphere,hospital level and type.Conclusions The readiness of clinical medical staff for remote health care is at a moderate level,but their willingness to participate in remote health care is high.It is recommended to construct a scientific and feasible remote health care training program for medical staff in the future to improve the quality of hospital services.

Objective:To compare the clinical efficacy of the H-Loop knotless double-row technique and the suture bridge technique in repairing L-shaped rotator cuff tears under arthroscopy.Methods:A retrospective analysis was performed on 58 patients with L-shaped rotator cuff injuries who underwent arthroscopic repair at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2019 and December 2021. The H-Loop knotless double-row technique was used in 16 cases (8 males and 8 females, mean age 63.69±8.78 years), while the suture bridge technique was used in 42 cases (24 males and 18 females, mean age 61.02±7.02 years). The American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles Shoulder Score (UCLA), Simple Shoulder Test (SST), shoulder range of motion, and muscle strength were evaluated and compared between the two groups one year after surgery.Results:The follow-up period was 12.81±0.98 months for the H-Loop group and 13.29±0.94 months for the suture bridge group. No significant differences were found between the groups in terms of age, sex, dominant hand, preoperative symptom duration, tear shape, tear size, or long head tendon amputation (P>0.05). The operative time was significantly shorter in the H-Loop group 67.50±16.02 minutes compared to the suture bridge group 76.67±13.19 minutes ( t=2.234, P=0.031). Additionally, the number of anchors used was significantly lower in the H-Loop group 2.00±0 compared to the suture bridge group 4.14±0.35 ( t=16.573, P<0.001). The ASES scores increased significantly in both groups: from 57.44±15.91 to 92.00±4.41 in the H-Loop group and from 58.21±16.58 to 87.71±6.19 in the suture bridge group ( F=53.439, P<0.001; F=72.511, P<0.001). Similarly, the UCLA scores improved from 20.63±3.79 to 31.56±3.65 in the H-Loop group and from 20.83±5.78 to 30.36±4.71 in the suture bridge group ( F=57.788, P<0.001; F=50.043, P<0.001). The Constant-Murley scores also showed significant improvement: from 68.50±15.31 to 87.5±8.70 in the H-Loop group and from 66.21±16.51 to 86.33±9.14 in the suture bridge group ( F=6.733, P<0.001; F=30.173, P<0.001). SST scores increased from 6.38±3.76 to 9.06±2.59 in the H-Loop group and from 6.55±3.31 to 9.17±2.45 in the suture bridge group ( F=2.847, P<0.001; F=11.096, P<0.001). The shoulder flexion range of motion increased from 158.75°±21.25° to 178.75°±47.07° in the H-Loop group and from 139.29°±45.12° to 179.76°±3.42° in the suture bridge group ( t=3.814, P=0.002; t=5.877, P<0.001). Shoulder abduction motion increased from 145°±45.46° to 178.75°±3.42° in the H-Loop group and from 135.24°±47.07° to 179.76°±1.54° in the suture bridge group ( t=2.952, P=0.001; t=6.185, P<0.001). Muscle strength improved from 53.36±25.21 N to 73.69±24.09 N in the H-Loop group and from 43.31±24.49 N to 61.8±30.07 N in the suture bridge group ( t=4.916, P<0.001; t=5.623, P<0.001). The ASES score at one year post-surgery was significantly higher in the H-Loop group 92.00±4.41 compared to the suture bridge group 87.71±6.19 ( t=2.529, P=0.014). There were no significant differences in UCLA scores, Constant-Murley scores, SST scores, shoulder motion, or muscle strength between the groups ( P>0.05). Conclusion:The H-Loop technique provides a good early curative effect. Compared to the traditional suture bridge technique, the H-Loop technique offers a higher early postoperative ASES score, shorter operative time, and fewer anchors required.

Objective:To evaluate the clinical efficacy of arthroscopic side-to-side suture with remnants preserved in repair of transtendinous rotator cuff tears.Methods:A retrospective study was conducted to analyze the data of 17 patients who had been treated by arthroscopic side-to-side suture with remnants preserved for transtendinous rotator cuff tear caused by trauma at Sports Medicine Center, The Second Hospital Affiliated to Inner Mongolia Medical University from January 2017 to January 2020. There were 11 males and 6 females with an age of (47.9±8.3) years and a duration from injury to surgery of (50.4±21.3) d. Recorded were range of motion and muscle strength of the shoulder, University of California at Los Angeles (UCLA) shoulder function score, Constant-Murley shoulder function score, visual analogue scale (VAS) pain score, re-tears and complications before operation and at the last follow-up.Results:The 17 patients were followed up for (16.5±3.5) months after operation. Retear of the rotator cuff occurred in 2 patients after operation while MRI showed good healing of the rotator cuff in the other patients with no such postoperative complications as infection or wound dehiscence. At preoperation and the last follow-up, respectively, the range of shoulder flexion was 152.9°±8.5° and 172.4°±5.6°, the abductor muscle strength 3.5 (2.6, 4.1) kg and 6.9 (6.3, 8.3) kg, the external rotator muscle strength (3.8±1.0) kg and (5.9±1.6) kg, the internal rotator muscle strength 3.9 (3.4,4.7) kg and 5.2 (4.5,5.9) kg, the UCLA score (13.2±1.9) points and (30.9±2.4) points, the Constant score (40.1±2.8) points and (86.1±4.6) points, and the VAS score (6.7±0.8) points and (0.9±0.6) points, all showing a significant difference between preoperation and the last follow-up ( P<0.05). Conclusion:In repair of transtendinous rotator cuff tears, arthroscopic side-to-side suture with remnants preserved can lead to significantly improved clinical outcomes in range of motion, muscle strength, functional recovery and pain relief.

Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.

Adult ; Cyclosporine ; Glomerulosclerosis, Focal Segmental/drug therapy* ; Humans ; Leflunomide/therapeutic use* ; Nephrosis, Lipoid/drug therapy* ; Nephrotic Syndrome ; Steroids

BACKGROUND: The proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) can delay the procession of steroid-induced femoral head necrosis. Besides, microRNA-141 (miR-141) is one of the important regulatory factors to promote cell proliferation. In addition, velvet antler is a traditional Chinese medicine which has significant roles in repairing bone and tissue and improving health. OBJECTIVE: To investigate whether velvet antler serum can regulate the expression of miR-141 to promote the proliferation of BMSCs, and further delay or reverse the progression of steroid-induced femoral head necrosis. METHODS: BMSCs were isolated and cultured from Sprague-Dawley rats. The passage 3 BMSCs were transfected with miR-141 mimic or miR-141 inhibitors, and then real-time PCR and methyl thiazolyl tetrazolium (MTT) assay were performed for detecting miR-141 expression and cell proliferation, respectively. The passage 3 BMSCs were divided into three groups: control group (α-MEM), dexamethasone group (α-MEM+1 μmol/L dexamethasone), and velvet antler serum group (α-MEM+1 μmol/L dexamethasone+15% velvet antler serum). Expression of miR-141 mRNA was detected by real-time PCR at 24 hours after intervention. The proliferation ability of BMSCs was evaluated by MTT assay at 24, 48, and 72 hours after intervention. RESULTS AND CONCLUSION: After transfection with miR-141 mimic, the expression of miR-141 mRNA was upregulated, while the cell proliferation was reduced. After transfection with miR-141 inhibitor, the expression of miR-141 mRNA was downregulated, while the cell proliferation was increased. The expression of miR-141 mRNA was significantly higher in the dexamethasone group than the control group (P < 0.01), while the treatment with velvet antler serum could significantly downregulate the expression of miR-141 mRNA (P < 0.01). The absorbance of BMSCs in the dexamethasone group was significantly lower than that in the control group (P < 0.01), and the absorbance value in the velvet antler serum group was significantly higher than that in the dexamethasone group (P < 0.01). In conclusion, the serum containing velvet antler can downregulate the expression of miR-141 which is upregulated by dexamethasone and then do help to promote the proliferation of BMSCs.

Objective:To explore the curative efficacy of pelvic reconstruction plate and T-plate elastic fixation in the treatment of acetabular fractures with comminuted posterior wall.Methods:A retrospective analysis was conducted of the 21 patients who had been treated at Department of Orthopaedics, Affiliated Hospital to the Second Mongolia Medical University for acetabular fractures with comminuted posterior wall from January 2017 to June 2019. They were 15 males and 6 females, aged from 29 to 55 years (average, 41.5 years). According to the Letournel-Judet classification, there were 15 cases of simple posterior wall fracture with dislocation of the femoral head, 4 cases of posterior wall and posterior column fracture, and 2 cases of double-column and posterior wall fracture. The time from injury to surgery averaged 3 days (from 2 to 5 days). The posterior acetabulum was treated by pelvic reconstruction plate combined with T-plate elastic fixation through the posterior acetabular Kocher-Langenbeck approach. Postoperative fracture reduction, fracture union time, function of the affected hip and complications at the last follow-up were evaluated.Results:This group of 21 patients were followed up for 6 to 24 months (average, 15 months). By the Matta imaging scoring, the postoperative reduction of the posterior wall fracture was evaluated as excellent in 18 cases and as good in 3, giving an excellent to good rate of 100%. The fracture union time averaged 10 weeks (from 8 to 12 weeks) for this group. By the improved Merle d'Aubigné & Postel evaluation at the last follow-up, the affected hips scored from 12 to 18 points (average, 16 points), yielding 18 excellent, 2 good and one poor cases, giving an excellent to good rate of 95.2%. There was no major hemorrhage, nerve injury or deep vein thrombosis intraoperatively. During the follow-up, mild ectopic ossification occurred in one case, and subluxation of the femoral head and traumatic arthritis were observed in another, but no patient had other complications like avascular necrosis of the femoral head.Conclusion:In the treatment of acetabular fracture with comminuted posterior wall, pelvic reconstruction plate and T-plate elastic fixation through the posterior acetabular Kocher-Langenbeck approach can lead to fine short-term outcomes.