Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a K_d of 0.18 μmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

Objective:To analyze the clinical and prognosis of children with kidney retransplantation.Methods:Clinical data of 11 children who underwent kidney retransplantation from January 2011 to December 2020 in Department of Nephrology, Children′s Hospital of Fudan University were retrospectilely analyzed. The clinical data including demographic parameters, primary diagnosis, characteristics in the follow-up of renal allograft were analyzed.Results:Totally 11 cases received secondary renal transplantation (male 6, female 5). They were initially diagnosed with chronic kidney disease at the age of 11.9 (7.4, 13.3) years. The median duration of dialysis was 22.1 (3.5, 36.5) months. In the first transplantation, recipient age was 13.9 (11.1, 15.2) years. Ten cases received donation from cardiac death donor (DCD) (9 cases received donors aged less than one year, 5 of them received whole kidney transplantation and one case received donor aged one to three years) and 1 case with living-related donor. Ten graft failures occurred within 1 month after renal transplantation and the other one occurred at the fifth month after transplantation. The causes included vascular factors (9 cases), rejection (1 case) and primary non-function (1 case). In the second transplantation, recipient age was 14.7 (11.7, 16.2) years. All the 11 children received dialysis (7 with PD and 4 with HD) and successfully completed the second transplantation. The median time between the two transplants was 210 (16, 1 041) days. Donors were all DCD donors from 3 years of age or older. The mean follow-up duration was (42±15) months. The estimated glomerular filtration rate was (85±34)ml/(min·1.73 m 2) when the last investigation after kidney retransplantation with the kidney and patient all survived. Conclusions:Kidney retransplantation may have better prognosis in children. Dialysis transition during waiting period and DCD donor from 3 years of age or older can effectively ensure the success of kidney retransplantation.

OBJECTIVE: To explore surgical methods and clinical effects of three different types of mini skin flap transplantation for repairing finger soft tissue with bone defect. METHODS: Thirty-three patients with finger soft tissue or bone defect were treated from December 2014 to October 2016, including 24 males and 9 females aged from 21 to 52 years old with an average of (36.42±5.70) years old, and soft tissue defect area ranged from 1.3 cm×1.8 cm to 2.3 cm×4.2 cm. According to damage degree, nature and patients' options, 15 finger of 15 cases were adopted retrograde dorsal metacarpal artery perforators fascia flap, 10 fingers of 9 cases were treated with free foot artery descending branch wrist skin flap, 9 fingers of 9 cases were treated with free the second toe details phalanges compound flap. Survival rate, postoperative complications and finger function assessed by Dargan functional criteria at the latest follow up were observed. RESULTS: All flaps were survived, both of donor site and recipient site were without deep infected. The donor site of one patient occurred necrotic, and the distal donor site of one patient occurred surface necrotic, then healed by active dressing change. All patients were followed up from 6 to 16 months with an average of(8.34±1.28) months. Two points of finger recognition were restored between 8 and 12 mm with an average of (8.84±0.43) mm, and the appearance, texture and sensory functions of skin flap were restored. No obvious complications were observed on the donor site. According to Dargan function evaluation of finger joints, 18 patients got excellent results, 14 moderate and 1 good. CONCLUSIONS Three kinds of mini skin flap could receive good results in repairing soft tissue of finger or bone defect. Reverse dorsal metacarpal artery perforator fascia flap is not necessary with anastomosing blood vessels and has advantages of safe, simple and high survival rate. Descending branch of superior cutaneous branch of free ulnar artery could cut multiple other perforator flaps simultaneously, and the scar is small and hidden. Dissociated the second toe combined metatarsal phalangeal flap could repair shape and function of finger to the maximum extent and donor site is hidden.
Adult ; Female ; Finger Injuries ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Skin ; Skin Transplantation ; Soft Tissue Injuries ; Treatment Outcome ; Young Adult

Objective: To assess the effect of combined treatment using cell scaffold and human fibroblast growth factor for small soft tissue defects of digits caused by trauma. Methods: From May 2012 to September 2016, twenty cases of small soft tissue defect of digits were repaired with cell scaffold combined with recombinant human basic fibroblast growth factor. The average defect area was 2.5 cm². Wounds were debrided and repaired with artificial dermis. Every 2 or 3 days the dressings were changed and the wounds were treated externally with fibroblast growth factor until cell scaffolds have been removed 3-4 weeks after surgery. Results: The group of 20 cases was followed up for 2-24 months. Wounds were healed with satisfactory appearance and no recurrence of wound or obvious hypertrophic scar was observed. No obvious functional problem was found in interphalangeal motion. Conclusions The method of repairing wound with cell scaffold combined with human fibroblast growth factor is simple and it result in healing of wounds with high quality.It provides a new choice for repairing wound in digits.

In July 2016, we used free superficial palmar branch of radial artery flap to repair one case of complete dissection of the thumb with skin defect, and achieved good result .

Laryngopharyngeal reflux is an independent disease that affects the quality of life in children,but its pathogenesis is not clear and its diagnostic criteria is not unified.With the reports of laryngopharyngeal reflux continuing to emerge in recent years,this study aims to review the progress in pathogenesis,diagnosis and treatment of laryngopharyngeal reflux in children.

OBJECTIVETo discuss the surgical method and clinical efficacy for open tarsometatarsal joint injuries.

METHODSFrom March 2011 to January 2015, 21 patients with open tarsometatarsal joint injuries were treated with stage-surgery method, including 14 males and 7 females with an average age of 45.6 years old ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6 cases, heavy crushing was in 10 cases. According to Myerson to classify for tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7 cases were type C2. And according to Gustilo to typing for soft tissue injury, 5 cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture healingand complications were observed after operation and clinical effects were evaluated according to the midfoot score of AOFAS.

RESULTSAll the patients were followed up from 11 to 40 months with an average of 16.2 months. The fracture healing time was from 10 to 16 weeks with an average of 12.3 weeks. No complications such as deep infection, nonunion and osteomyelitis were found. Midfoot score of AOFAS at last follow-up was 83.0±14.9, 9 cases got excellent results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic arthritis once again underwent tarsometatarsal arthrodesis.

CONCLUSIONSFor the treatment of open tarsometatarsal joint injury, reasonable debridement, comprehensive assessment for the soft tissue injury, correctly grasp the surgical indications and time of internal fixation, can reduce the incidence of deep infection and osteomyelitis.

Objective: To investigate the clinical effect of a novel disposable ring versus that of the suture device in circumcision for redundant prepuce and phimosis. METHODS: We randomly assigned 470 male patients with redundant prepuce or phimosis to receive circumcision with a novel disposable ring (the DR group, n = 235) or the suture device (the SD group, n = 235) and compared the operation time, intraoperative blood loss, pain scores, wound healing time, and postoperative complications and penile appearance between the two groups of patients. RESULTS: All the operations were completed smoothly. Compared with the SD group, the DR group showed significantly shorter operation time (［7.49 ± 1.84］ vs ［3.83 ± 0.42］ min, P <0. 05), less intraoperative blood loss (［3.34 ± 2.59］ vs ［2.41 ± 1.01］ ml, P <0.05), lower intraoperative pain score (0.57 ± 0.76 vs 0.20 ± 0.47, P <0.05) and 6-hour postoperative pain score (3.42 ± 1.12 vs 0.48 ± 0.94, P <0.05), shorter wound healing time (［12.05 ± 2.80］ vs ［7.79 ± 1.65］ d, P <0.05), lower incidence rates of postoperative glans congestion or edema (36.17% ［85/235］ vs 2.56% ［6/235］, P <0.05), dysuria or strenuous urination (34.04% ［80/235］ vs 2.13% ［5/235］, P <0.05) and bleeding or hematoma (5.11% ［12/235］ vs 1.28% ［3/235］, P <0.05), and higher satisfaction with postoperative penile appearance (90.6% ［213/235］ vs 95.8% ［228/235］, P <0.05). There were no statistically significant differences between the SD and DR groups in the pain scores at the sixth night after operation (1.31 ± 0.96 vs 1.34 ± 1.07, P >0.05) or while the staples scraping the underpants or at the ring removal (3.49 ± 1.22 vs 3.36 ± 1.41, P >0.05). No obvious postoperative infection or delayed healing was observed except for 3 cases of wound dehiscence (1 in the DR and 2 in the SD group) and 8 cases of delayed removal of the staples in the SD group. CONCLUSIONS The novel disposable ring, with its advantages of short operation time, less bleeding and pain, good penile appearance, high safety, and simple operation, is obviously superior to the suture device in circumcision and deserves to be applied and popularized clinically. .
Blood Loss, Surgical ; Circumcision, Male ; instrumentation ; Disposable Equipment ; Edema ; etiology ; Humans ; Male ; Operative Time ; Pain Measurement ; Pain, Postoperative ; Penis ; abnormalities ; surgery ; Personal Satisfaction ; Phimosis ; surgery ; Postoperative Complications ; etiology ; Postoperative Period ; Suture Techniques ; instrumentation ; Sutures ; Wound Healing