Exploration of the relationship between nicotinamide metabolism-related genes and osteoarthritis / 上海交通大学学报（医学版）

Objective·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis,and identify key genes with diagnostic value and therapeutic potential.Methods·By using"Osteoarthritis"as a search term,GSE12021,GSE55235,and GSE55457 were obtained from the GEO database,with GSE55457 being used as the validation set.After removing batch effects from the GSE12021 and GSE55235 datasets,the standardized combined dataset was obtained and used as the training dataset.Differentially expressed genes(DEGs)were identified from the training dataset.All nicotinamide metabolism-related genes(NMRGs)were obtained from the GeneCards and MSigDB databases.The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes(NMRDEGs).Gene set enrichment analysis(GSEA)was performed on the training dataset,while gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed on NMRDEGs.Key genes were selected by using least absolute shrinkage and selection operator(LASSO)and support vector machine(SVM)analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset.Single sample gene set enrichment analysis(ssGSEA)was used to analyze the immune cell infiltration type.Interactions networks and drug molecule predictions were obtained for these key genes'mRNA with the DGIdb,ENCORI,and CHIPBase databases.siRNA was used to knock down the key genes in chondrocytes,and then real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of chondrogenesis-related genes.Results·Seven NMRDEGs,including NAMPT,TIPARP,were discovered.GO and KEGG analysis enriched some signaling pathways,such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway.GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway.Key genes NPAS2,TIPARP,and NAMPT were identified through LASSO and SVM analysis,and used to construct an osteoarthritis diagnostic model.The validated results showed that the diagnostic model had high accuracy.Immune infiltration analysis results obtained by ssGSEA showed significant differences(all P<0.05)in 15 types of immune cells,including macrophages.Seven potential small molecules targeting key genes were identified,along with 19 miRNAs with the sum of upstream and downstream>10,19 transcription factors with upstream and downstream>7,and 27 RNA binding proteins with clusterNum>19.The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes.Conclusion·Through bioinformatics analysis,key genes related to nicotinamide metabolism,NPAS2,TIPARP,and NAMPT,are discovered,and an osteoarthritis diagnostic model is constructed.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Dare to be the first, persistent efforts will pay off / 中华显微外科杂志

In July 1973, the Laboratory of Limb Replantation of Shanghai Sixth People's Hospital pioneered a functional transfer of a muscle belly to replace a group of forearm flexor muscles which had lost the function due to ischemic contracture. Flexion activity of digits was effectively reconstructed and good results were achieved by the muscle transfer. It was the very first successful surgery for functional muscle transfer in the world. The surgery made the Chinese microsurgical techniques at a new height with a great historical significance in global surgery. With hard explorations and works of generations, many new breakthroughs in microsurgery had been made over the last half a century. However, we never forget the hard works and wisdom pioneered by the surgeons in previous generations over the past. Their spirits in depth cultivation of clinical sciences and their attitudes towards scientific exploration and research have been inspiring today’s younger generation. On the occasion of the 50th anniversary celebration, I would like to dedicate this article to all the predecessors and colleagues who pioneered functional muscle transfer and contributed to the successful cause of microsurgery in China. All of us should keep to persist with our best efforts and continue to promote the high-quality development of repair and reconstructive microsurgery in China, benefit the patients and serve a satisfactory healthcare for the people.

Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023) / 中华创伤杂志

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023) / 中华创伤杂志

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Expert consensus on platelet-rich plasma treatment for osteochondral lesion of talus (version 2023) / 中华创伤杂志

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Efficacy of staged treatment for calf Gustilo-Anderson type IIIC fracture / 中华创伤杂志

Objective:To evaluate the clinical efficacy of staged surgery in treatment of calf Gustilo-Anderson type IIIC fracture.Methods:A retrospective case series was conducted to analyze clinical data of 16 patients with calf Gustilo-Anderson type IIIC fracture admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2017 to December 2019. There were 12 males and 4 females, with the age of (38.6±8.2)years (range, 18-53 years). All patients had limb salvage treatment at one stage in the emergency department. The survival of the limb and the occurrence of vascular crisis were examined within one week after limb salvage. The second stage involved the repair of skin and soft tissue defects with the defect area from 12.0 cm×5.0 cm to 20.0 cm×8.0 cm using free flaps. The survival of the flap, vascular crisis, and donor site healing within two weeks after the flap procedure. The third stage used bone graft revision and bone lengthening technology to repair bone tissue. The lower extremity functional scale (LEFS) and Mazur ankle joint function score were used to evaluate the function of the affected limb before bone repair and at the last follow-up. The fracture healing and related complications were observed at the last follow-up.Results:All patients were followed up for (14.2±4.6)months (range, 8-20 months). At one stage, the limb-saving surgery was successful in all patients, among which one had vascular crisis. At second stage, free flaps survived in all patients, among which two had vascular crisis. All donor areas were healed by first intention. At third stage, the LEFS of the affected limb was increased from (32.0±7.4)points before bone repair to (48.0±10.2)points at the last follow-up ( P<0.01) and the Mazur score was increased from (50.9±15.3)points before bone repair to (73.8±11.9)points at the last follow-up ( P<0.01). All bone defects were repaired and healed without complications such as infection or osteomyelitis at the last follow-up. Conclusion:For calf Gustilo-Anderson type IIIC fracture, the staged strategy can effectively save limbs and restore limb function.

Influences of structural changes after valgus impacted femoral neck fracture on hip range of motion: a 3D simulation test / 中华创伤骨科杂志

Objective:To determine the influences of structural changes after valgus impacted femoral neck fracture on hip range of motion (ROM) so as to provide evidence for clinical judgment of whether reduction is necessary or not in the internal fixation of such fractures.Methods:1. 3D reconstructions of the CT hip scans were performed for the 73 patients who had been treated at Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University for valgus impacted femoral neck fractures from January 2019 to April 2019.The femoral neck-shaft angle, anteversion angle, femoral offset, axial alpha angle, lateral center edge angle (LCEA), anterior center edge angle (ACEA) and center displacement were measured and compared between the affected and healthy sides to determine the influences of the fracture on the above indexes. 2. Hip motions (flexion and MIR-90°) were simulated on bilateral sides to determine the influences of structural changes after fracture on hip ROM using stepwise regression and Logistic regression. 3. The distribution of femoral-acetabular contact points on the femoral side was observed in simulation of hip flexion to detect the potential area for femoracetabular impingement (FAI) induced by the fracture displacement.Results:1. The valgus impacted femoral neck fractures had significant influences on femoral neck-shaft angle, anteversion angle, femoral offset and axial alpha angle. Compared with the healthy side, on average, the femoral neck-shaft angle increased by 5.1°, anteversion angle decreased by 6.5°, femoral offset decreased by 8.2 mm and axial alpha angle increased by 9.7° on the affected side, showing significant differences ( P<0.05).The displacements of the femoral head center averaged 9.2 mm. There was no significant difference in LCEA or ACEA between the affected and healthy sides ( P>0.05). 2. Compared with the healthy side, on average, the simulated hip flexion decreased significantly by 27.0° and the hip MIR-90° decreased significantly by 20.3° on the affected side after fracture ( P<0.05). Regression analysis showed that femoral anteversion angle, ACEA and displacement of the femoral head center had a significant influence on hip ROM, especially the anteversion angle. When the anteversion angle decreased by more than 7.1°, the hip flexion would decrease by at least 20%. 3. The points of FAI distributed more widely on the fracture side. Compared with the healthy side, the impact points extended outward and upward in hip flexion and extended inwardly in hip MIR-90° on the affected side. Conclusions:After a valgus impacted femoral neck fracture, if the femoral anteversion angle has been decreased by more than 7.1°, the hip ROM can be greatly influenced and the points of FAI can be distributed more widely. Therefore, reduction should be recommended before internal fixation of the fracture.

Establishment of preoperative diagnosis of low-grade infectious nonunion / 中华创伤骨科杂志

Objective:To explore the reliability of preoperative diagnosis of low-grade infectious nonunion using haematological testing and radioisotope scanning (bone 3-phase image).Methods:A retrospective study was conducted of the 265 patients with bone nonunion who had been treated at Department of Orthopaedics, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University and at Department of Orthopaedics, The Eighth People’s Hospital Affiliated to Shanghai Jiaotong University from June 2010 to June 2018.They were 151 males and 114 females, aged from 19 to 64 years (average, 39.7 years).The nonunions occurred mainly at the tibia (113 cases) and the femur (72 cases).The preoperative results of their white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and radioisotope scanning were recorded.Taking the intraoperative pathological observations as the gold standards, the sensitivity, specificity, area under curve (AUC) of receiver operator characteristic (ROC) and Youden index were statistically analyzed respectively for every preoperative haematological tests and radioisotope scanning as well as for different combinations of the radioisotope scanning and one or more haematological tests.Results:Compared with the pathological observations, the radioisotope scanning showed a sensitivity of 80.7%, a specificity of 73.3%, an AUC of 0.770 and a Youden index of 0.540.In the combinations of radioisotope scanning and one haematological test, that of radioisotope scanning and CRP produced the largest AUC of 0.683, a sensitivity of 98.0%, a specificity of 70.3%, and a Youden index of 0.848.In the combinations of radioisotope scanning and 2 haematological tests, that of radioisotope scanning and WBC and ESR produced the largest AUC of 0.895, a sensitivity of 94.3%, a specificity of 67.3%, and a Youden index of 0.616 and all the 3 ones yielded an AUC of more than 0.880.The combination of radioisotope scanning and all the 3 haematological tests produced a sensitivity of 96.5%, a specificity of 79.7%, an AUC of 0.925 and a Youden index of 0.762.Conclusion:Combination of haematological testing and radioisotope scanning can be a reliable preoperative diagnosis of low-grade infection nonunion.

Clinical application of posterior tibial artery perforator flap within saphenous nerve branch for sensory reconstruction / 中华显微外科杂志

Objective To explore the operative technique and clinical results of posterior tibial artery perforator flap within saphenous nerve branch for sensory reconstruction.Methods From January,2016 to June,2018,9 patients suffered from soft tissue defect were treated by the posterior tibial artery perforator flap containing saphenous nerve branch.Seven patients were males and 2 were females,with age ranged from 31 to 62 years.Soft tissue defects located in hands in 5 patients,plantar in 2 patients,ankle in 1 patient and dorsal foot in 1 patient.The size of soft tissue defects ranged from 8.0 cm×2.5 cm to 21.0 cm×4.0 cm.The regular post-operative followed-up was performed.Results All flaps survived without complications.The size of flap ranged from 10.0 cm×3.5 cm-23.0 cm×5.0 cm.Donor sites were primarily closed in 5 patients and secondary closed in 4 patients.Followed-up ranged from 6 to 15 months with 10 months in average.The contour of flaps were satisfied and the sensory function of the donor sites were normal.At 6 months followed-up,SW test reached 5.07 in all flaps,and 2PD ranged from 14 to 35 mm.Conclusion The novel sensory flap can provide satisfied sensory outcome without sacrificing main artery and saphenous nerve,and is a good candidate for sensory reconstruction of soft tissue defects.

Vertical Neck angle and long-term outcomes of femoral neck fractures treated with cannulated screws / 中华创伤骨科杂志

Objective To analyze the associations between long-term outcomes of fresh femoral neck fractures treated with cannulated screws and the classification based on vertical neck (VN) angle.Methods A retrospective study was conducted of the 162 fresh femoral neck fractures treated with 3 cannulated screws at Department of Orthopaedics,The Sixth People's Hospital of Shanghai from January 2012 to December 2014.The relationships were analyzed using Logistic Regression between long-term complications and VN classification,including fixation failure,fracture nonunion and osteonecrosis of femoral head (ONFH).Results All the patients were followed up for an average of 25.7 months (from 6 to 36 months).Of them,151 obtained fracture union after an average of 4.5 months (from 3 to 9 months).Internal fixation failure occurred in 23 cases,nonunion of femoral neck in 11,ONFH in 21 and femoral neck collapse in 13.Logistic Regression analysis showed no significant associations between internal fixation failure,nonunion or ONFH and gender,age or reduction method (P ＞ 0.05) but significant associations of VN classification with fixation failure (P ＜ 0.001) and nonunion (P =0.001) and insignificant association of VN classification with ONFH (P =0.109).Conclusion VN classification,a new classification method for femoral neck fractures,may be closely related with incidences of fixation failure and nonunion.

Reduction techniques and choice of internal fixation for young femoral neck fractures / 中华创伤骨科杂志

Femoral neck fractures are not common in young patients,accounting for merely 3％ of all these fractures.However,since the young femoral neck fractures are mostly caused by high energy violence,they usually jeopardize local blood supply and mechanical environment,resulting in higher risks of non-union and avascular necrosis.Besides,young patients often make a greater demand for functional recovery.Consequently,young femoral neck fracture is always a clinical challenge.In this article,we introduce in details the latest techniques and standards for reduction of young femoral neck fracture,compare advantages and drawbacks of various internal fixations,illustrate up-to-date progress in treatment methods and concepts for delayed and nonunited femoral neck fractures,and lastly put forward some unsolved issues open to dispute.In treatment of young femoral neck fractures,it is necessary for us to get familiarized with their anatomy and biomechanical characteristics,grasp the principles of treatment on the whole,and choose operational and internal fixation methods based on the clinical evidence before we can improve therapeutic efficacy,accelerate rehabilitation progress and restore function of the hip joint as much as possible.

Development on a hip functional score of adults based on patient-reported outcomes / 中华骨科杂志

Objective To develop a simple and patient-reported scoring system for evaluating the efficacy of functional reconstruction of adult hip diseases.Methods A candidate indicators list to evaluate hip function was established through literatures review and panel discussion.Using two rounds of Delphi method,experts were invited to judge and score the importance of screening indicators including pain,daily living ability,activity level,labor ability and self-assessment score of the overall hip status,with explanation of the degree of similarity and the basis for determination.In the second round of consultation,the content of integrity and rationality of the scale were added for evaluation.The final indexes of the scale were determined according to the boundary value of the indexes (average value,full frequency,coefficient of variation).The positive coefficient,authoritative coefficient,and coordination coefficient of the two rounds were calculated,and then the weights of each index was identified to form the final rating scale.Results Two rounds of Delphi reclaimed 25 and 24 experts' responses,which from 28 and 25 questionnaires,and the positive coefficients of the two rounds experts were 89.3％ and 96％,respectively.The authoritative coefficient of the first and second level indicators were generally above 0.85;and both of the expert coordination coefficient with the index importance (so called as Kendall coefficient) were above 0.3,and the second round of the coefficient was higher than the first one,and it indicated the final one was better at the consistency.The candidate index of "by bus" in the mobility was rejected in accordance with the threshold of the boundary value on the importance.Finally,it was determined that the hip scoring system (Shanghai Sixth People's Hospital,SSPH) consisted of two parts:the first part had ten indicators out of four dimensions such as pain,daily living ability,activity level,and labor ability;and the weight scores of these four aspects were 45,25,21,9,respectively.The second part was the patient's self-evaluation score for the overall status of the hip (VAS,out of 100 points);the total score was the sum of the two parts,and the final weights accounted for 85％ and 15％ between the two parts respectively.Conclusion The SSPH hip score based on patient-reported outcomes formed by the Delphi is simple and feasible,and it can be used as a reference for evaluating the clinical efficacy of hip functional reconstruction.

Ten years retrospective study of using primary microsurgery technology to treat patients with severe lower extremities injury / 中华显微外科杂志

Objective To clarify the role of microsurgery in limb salvage procedure and its efficiency in long-term functional results through a retrospective review of patients who sustained severe injury of lower extremities and had been treated Shanghai 6th people's hospital, in recent 10 years. Methods Patients who sustained severe injury of lower extremities and treated with microsurgical techniques in January, 2006 to January, 2016 were studied. Patients' general information, classification of open fracture, and MESS were noted. The enrolled patients were divided into two groups (group A: primary microsurgical reconstruction;group B: non-microsurgical reconstruction ) according to whether primary microsurgical reconstruction was performed or not. Each group were also further divided into sub-group according to preoperative MESS (MESS<7 and MESS≥7). The reconstruction methods, hospitalization days, op-eration times, postoperative complications, as well as the SIP were then recorded for each groups. The differences of these data among each groups were analyzed and compared. Results The main objection was patient with Gustilo grade III open fracture, totally 548 patients were admitted, with 312 males and 236 females. The main age was 35.6 years old. The main etiology was road traffic accident (79.7％). There were 211 patients (38.5％) in group A, and 337 patients (61.5％) in group B. In group A, there were 37 patients in subgroup one (MESS<7), and 174 patients in sub-group two (MESS≥7). The rate of delayed amputation was 2.8％, while the complication rate was 11.8％. In group B, there were 181 patients in subgroup one(MESS<7), and 156 patients in subgroup two (MESS≥7). The rate of delayed amputation was 4.0％, while the complication rate was 13.3％. In long-term survey, the average VAS score of group B was higher than that of group A, but no significant difference was noted. The average VAS scores in 2 year postopera-tively in the subgroups (MESS≥7) were higher than those in the other subgroups (MESS<7). The results of SIP scores were similar with VAS scores in two groups. Conclusion The techniques of microsurgery has been promoting the successful rates and outcomes for limb salvage procedure over the recent decades. Meanwhile, the current evaluating system for se-vere limb injury needs to be updated to meet the demands of ever-developing limb salvage techniques.

Role of endoplasmic reticulum stress in omega-3 polyunsaturated fatty acids supplementation for attenu-ating inflammatory response in experimental rat models of colitis / 中华临床营养杂志

Objective To investigate the effects and mechanisms of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on colonic macroscopic and histological score , inflammatory response , and endo-plasmic reticulum stress ( ERS ) response in experimental rat models of colitis .Methods Experimental rat models of colitis were induced by trinitro-benzene-sulfonic acid (TNBS).Totally 100 male SD rats were ran-domly divided into 5 groups according to the random data tables:sham operation group ( Sham group ) , inflam-matory bowel disease group (IBD group),ω-3 PUFA supplementation group (IBD+ω-3 group), 5-aminosali-cylic acid group ( IBD +5-ASA group ) , and ERS activation 2-deoxy-D-glucose group ( IBD +ω-3 +2-DG group).Colonic macroscopic and histological scores were evaluated on days 1, 3, 7 and 14 after modeling.The serum levels of tumor necrosis factor-α(TNF-α), interleukin (IL) -1, and IL-6 were measured using en-zyme-linked immunosorbent assay , whereas ERS cytokines including glucose-regulated protein 78 ( GRP78 ) , inositol-requiring enzyme 1 (IRE-1), and C/EBP homologous protein (CHOP) were tested by Western blot. Results Compared with the Sham group , colonic macroscopic and histological score , the serum levels of in-flammation relatived factors (TNF-α, IL-1, IL-6) and ERS relatived factors (GRP78、 IRE-1, CHOP) were significantly increased on the rest of the four groups ( all P<0.001 ) .Compared with the IBD group , ω-3 PUFA supplementation reduced colonic macroscopic [7 d: 3.55 ±0.29 vs.4.37 ±0.39, P=0.03, 14 d:2.46 ±0.17 vs.3.86 ±0.21, P=0.04] and histological score [7 d: (2.56 ±0.27) scores vs.(3.45 ± 0.40) scores, P=0.02, 14 d: (2.23 ±0.20) scores vs.(3.06 ±0.26) scores, P=0.04].Meanwhile,ω-3 PUFA supplementation suppressed the expressions of inflammation [TNF-α:(43.71 ±11.39) pg/ml vs. (84.97 ±13.81) pg/ml, P=0.02, IL-1:(38.51 ±10.60) pg/ml vs.(73.04 ±12.48) pg/ml, P=0.01, IL-6:(28.91 ±7.27) pg/ml vs.(53.45 ±9.40) pg/ml, P=0.02] and ERS relatived factors (GRP78:2.41 ±0.29 vs.1.47 ±0.21, P=0.01, IRE-1:2.83 ±0.31 vs.1.23 ±0.20, P<0.001, CHOP:1.89 ± 0.17 vs.1.32 ±0.11 , P=0.04 ) .However , the salutary effects of ω-3 PUFA would been reversed by ERS activation 2-deoxy-D-glucose [ TNF-α: (72.67 ±10.37 ) pg/ml vs.(43.71 ±11.39 ) pg/ml, P =0.02, IL-1:(57.66 ±13.88) pg/ml vs.(38.51 ±10.60) pg/ml, P=0.02, IL-6: (46.10 ±9.67) pg/ml vs. (28.91 ±7.27) pg/ml, P=0.01, GRP78:1.47 ±0.21 vs.1.82 ±0.24, P=0.03, IRE-1:1.23 ±0.20 vs.2.21 ±0.23, P=0.02, CHOP:1.32 ±0.11 vs.1.61 ±0.16, P=0.04].Conclusion The salutary effects of ω-3 PUFA supplementation on the colitis induced by TNBS appear to be mediated by inhibited inflam -matory responses , which may suppress the activation of ERS response .

Relationship Between Cardiac Myosin-binding Protein c.G772A Gene Mutation and Familial Hypertrophic Cardiomyopathy / 中国循环杂志

To investigate the mutation site of pathogenic gene in patients with hypertrophic cardiomyopathy (HCM) and to analyze the relationship between the genotype and clinical phenotype. Methods: Targeted exon capture sequencing was conducted in a HCM proband for 30 coding exons related HCM gene by all exon amplification and high-throughput sequencing. Furthermore, Sanger sequencing was performed in other family member and in 200 healthy volunteers for verification. The familial investigation included in clinical presentation, physical examination, electrocardiogram and echocardiography. Results: There were 3/6 blood relatives carrying cardiac myosin-binding protein gene MyBPC3 G772A heterozygous mutation, the mutation site was at 258 amino acid of MyBPC3 as glutamic acid (Glu) was substitute to lysine (Lys), such mutation was not found in rest of family member and not in healthy volunteers. The onset of proband and her daughter was rather late, they had palpitation and chest tightness; echocardiography showed interventricular septum basal segment thickening (16-18) mm. Proband was complicating paroxysmal ventricular tachycardia, malignant arrhythmia and heart failure, the maximum pressure gradient of left ventricular outflow was 56 mmHg, which with the high risk for sudden death. Conclusion: Comprehensive gene test has been helpful for clinical stratification, early diagnosis and treatment. MYBPC3 site mutation c.G772A might be the pathogenic mutation in that specific HCM family.

Progress in diagnosis and care of fractures of the femoral head / 中华骨科杂志

Fractures of the femoral head (FFH) are mainly seen in young adults,and the majority mechanism is due to dashboard injury in crushing vehicles.FFH can be present with or without posterior dislocation of the hip joint.Except for periarticular pain and hip dysfunction,the typical signs include flexion,adduction and internal rotation of the hip and shortening of involved limb.CT and MRI get their popularity as diagnostic methods for FFH.An emergency open reduction should be indicated in the scenario of failed closed reduction in FFH with posterior dislocation,of FFH with femoral neck fractures,of unmatched head and acetabulum following closed reduction and of deteriorating sciatic nerve damage.Pipkin as well as Brumback classification is still the most popularly used methods,which have great significance for establishment of surgical strategy and prediction of prognosis.More and more clinical evidences show conservative care of FFH should only be indicated for non-displaced fractures or displacement less than 2 mm.These cases must meet the following criteria simultaneously,including stable hip joint,concentric head and acetabulum,no free fractured fragments in the joint space and no labrum entrapment.Operative care is naturally the treatment of choice.Surgical approaches for FFH are hot topics in recent years.In previous control studies to compare Kocher-Langenbeck (K-L) and Smith-Peterson (S-P) approach,it is revealed less operative time,less blood loss and better operative field you can get in S-P approach,however,the incidence of ectopic ossification is higher.Ganz approach,which is characterized by osteotomy of great trochanter,hip capsulotomy and surgical dislocation of the hip,is a novel pattern for operative care of FFH.Ganz approach can show the entire femoral head,while can not damage medial femoral circumflex artery (MFCA) and induce iatrogenic osteonecrosis of the femoral head (ONFH).Various screws are the main implants for the fixation of fractured femoral head.Osteoarthritis and ONFH are two principal complications following FFH,which not only closely associate with severity and mechanism of primary injury,but also correlate with reduction quality and iatrogenic factors.Artificial hip joint replacement is a rational choice for extremely comminuted femoral head and these FFH in the elderly.

Comparative study of arthroscopic coracoacromial ligament augmentation and clavicular hook plate for treatment of acromioclavicular joint dislocation / 中华创伤杂志

Objective To compare the outcomes of arthroscopic coracoacromial ligament augmentation and clavicular hook plating in treatment of acromioclavicular joint dislocation.Methods From March 2008 to March 2012,47 patients with acute closed type Ⅲ-Ⅴ acromioclavicular joint dislocations underwent an arthroscopic repair with coracoacromial ligament augmentation and suture (ligament augmentation group,23 patients) and with AO clavicular hook plate (hook plate group,24 cases).Mean age of the patients (32 males and 15 females) was 34.8 years (range,17-45 years).There were 32 left and 15 right injuries.Postoperative outcome was assessed through radiographic examination,American Shoulder and Elbow Surgeon (ASES) score and Karlsson scoring method.Results Mean period of follow-up was 18 months (range,12-24 months).In ligament augmentation group ASES score improved from (28.7 ± 7.3) points preoperatively to (96.3 ± 6.9) points postoperatively (t =51.34,P ＜ 0.05).In hook plate group ASES score improved from (29.3 ± 7.6) points preoperatively to (83.6 ± 8.5) points postoperatively (t =43.78,P ＜ 0.05).Postoperative radiographic examination showed well joint reduction of all patients.Good and excellent results with the Karlsson score accounted for 96％ (22/23) in ligament augmentation group and 71％ (17/24) in hook plate group (x2 =9.05,P ＜0.05).Conclusions Efficacy of coracoacromial ligament augmentation and suture for the treatment of acromioclavicular joint dislocation is better than clavicular hook plate.Coracoacromial ligament augmentation and suture are associated with lower incidence of shoulder pain and shoulder activity limitation,shorter recovery time,fewer complications and early activities.

Synthesis of two related substances of everolimus / 中国药科大学学报

@#To optimize the synthesis and purification process of everolimus, and to investigate the quality of everolimus, synthetic schemes were designed to prepare 2 related substances, resulting from the process of everolimus. These two related substances were 28, 40-O, O′-bis(2-hydroxyethyl)rapamycin and 28-O-(2-hydroxyethyl)rapamycin. Their structures were confirmed by 1H NMR and MS, and their presence in everolimus was confirmed by HPLC.