OBJECTIVE: To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint. METHODS: The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions. RESULTS: The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone. CONCLUSION The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans ; Finite Element Analysis ; Knee Joint/physiology* ; Tibia/anatomy & histology* ; Cartilage, Articular/physiology* ; Menisci, Tibial/physiopathology* ; Tomography, X-Ray Computed ; Osteoarthritis, Knee/diagnostic imaging* ; Weight-Bearing ; Bone Density ; Adult ; Stress, Mechanical ; Male ; Middle Aged ; Biomechanical Phenomena ; Female

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:To explore the short-term outcomes of reconstruction of tumorous critical bone defects at femoral shaft with a 3D printed ultra-short stem with a porous structure.Methods:From September 2016 to June 2018, 8 patients underwent reconstruction of critical bone defects with a 3D printed ultra-short stem with a porous structure after resection of femoral shaft malignant tumor at Department of Orthopaedics, West China Hospital. There were 4 males and 4 females, with an average age of 36.9 years (from 11 to 61 years). Their preoperative Enneking staging was stage Ⅱb in all. There were 3 osteosarcomas, 2 Ewing sarcomas, 2 chondrosarcomas and one periosteal osteosarcoma. Preoperative CT/MRI image fusion technology was used to define the surgical boundary, design the guide plate and prosthesis, and perform surgical simulation. Tomosynthesis-shimadzu Metal Artefact Reduction technology was used to evaluate osseointegration. Complications and bone oncology prognosis of the patients were documented. The lower limb function of the patients was evaluated using Musculoskeletal Tumor Society (MSTS) 1993 scoring and knee range of motion.Results:The overall follow-up time ranged from 36 to 50 months, averaging 42.8 months. During operation one patient sustained a periprosthesis fracture, the union of which was followed up after wire assisted fixation. There was no local tumor recurrence, lung metastasis or death. The last follow-up revealed good osseointegration and basically isometric lower extremities in all cases. There was no such a complication as aseptic loosening of the prosthesis, deep infection or prosthesis fracture during the follow-up period. At the last follow-up in the 8 patients, the flexion range of the knee joint was 116.2°±9.1°, significantly improved compared with that before operation (98.8°±10.9°), and the MSTS score was (26.2±2.1) points, also significantly improved compared with that before operation [(21.6±1.8) points] ( P<0.05). Conclusions:Reconstruction with a 3D printed ultra-short stem with a porous structure is an accurate operation for femoral shaft tumorous bone defects. With careful preoperative design, intraoperative manipulation and strict postoperative follow-up management, this operation can lead to fine early curative outcomes for long shaft critical bone defects.

Objective To evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods Totally, 2219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1％, 1755/2219) and the placenta percreta (PP) group (20.9％, 464/2219), according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ2=157.961) and placenta previa (χ2=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

Atherosclerosis is a chronic systemic inflammatory disease caused by the interaction of environment and genetic factors. Epigenetic modification is a bridge between environmental factors and genetic factors. DNA methylation is an important regulatory mode of epigenetic modification, which can regulate gene expression at the pre-transcriptional level. Studies have shown that DNA methylation plays an important role in the occurrence and development process of atherosclerosis. Therefore, atherosclerosis-related DNA demethylation, especially carotid atherosclerosis-related DNA demethylation, can be achieved by natural or synthetic DNA demethylases, thereby achieving the purpose of preventing or treating atherosclerotic cerebrovascular disease. This article reviews DNA methylation and its relationship with atherosclerosis and DNA demethylation therapy.

Objective:To develop the Abusive Behavior Scale for Superiors under the Chinese context (ABSSC) and test its validity and reliability.Methods:Based on literature analysis and the open questionnaire survey in 32 employees,this study defined the construct of ASBSS,and compiled the preliminary questionnaire.A sample of 200 employees coming from companies was selected for item analysis.A sample of 445 employees was investigated with this questionnaire,223 of them were assessed for exploratory factor analysis and 222 of them were assessed for confirmatory factor analysis and internal consistency test with 2 week interval.Results:The ABSSC consisted of 11 items in 3 factors,which were neglect and slander,obstructionism and hard on subordinates.The 3 factors explained 55.45％ of the total variance.Furthermore,the result of CFA indicated that the model fitted the data with well constmct validity (RMSEA =0.06,GFI =0.94,NFI =0.92,CFI =0.96,IFI =0.96).The Cronbach α coefficient of the whole scale and its three facts were 0.87,0.79,0.78,and 0.76,respectively.Conclusion:It suggests that the Abusive Behavior Scale for superiors under the Chinese context (ABSSC) is reliable and valid enough to be applicable to measure superiors' abusive behavior under the background of Chinese culture.

Vertebrobasilar dolichoectasia(VBD ) can increase the risk of stroke. Significant expansion, elongation and tortuosity of the vertebrobasilar arteries are the main morphology manifestations of VBD. However, there is no consensus on the quantitative imaging assessment of VBD. Many studies showed that some quantitative parameters, such as basilar artery length and bending length, basilar angulation, vertebral tortuosity index can be used for the quantitative imaging assessment of VBD.

Objective To detect serum brucellosis in high risk population,three methods were used and their advantages and disadvantages was compared.Methods In accordance with the surveillance standard for brucello-sis(GB 16885 -1997)and brucellosis diagnostic criteria(WS269 -2007)in the prescribed method,rose -bengal plate agglutination test (RBPT),standard -tube agglutination test (SAT)and enzyme linked immunoassay assay (ELISA)were used to detect brucellosis and analysis of its diagnostic significance in the high risk population of sheep farm of Guoyang county in Anhui province.Results The positive rates of RBPT,SAT and ELISA were 19.1%,12.1% and 16.3% in 257 blood samples,respectively.Compared to SAT,the sensitivity,specificity,accura-cy and the area under the ROC curve of RBPT were 88.5%,91.8%,91.4%,0.81,respectively,which of ELISA were 93.9%,95.1%,94.9%,0.88.Conclusion The sensitivity,specificity,accuracy and the area under the ROC curve of ELISA were higher than those of other methods.Proper method,early surveillance and effective technology can help to control the occurrence and epidemic of brucellosis in the actual test work promotion.