BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.

BACKGROUND:The incidence of medial collateral ligament injuries in the knee joint is easy to lead to secondary meniscus and cartilage damage,and long-term chronic damage can lead to the occurrence of osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by medial collateral ligament rupture. OBJECTIVE:To investigate the effect of different degrees of medial collateral ligament injury on the biomechanics of meniscus and cartilage of knee joint. METHODS:The CT and MRI examinations of the knee joint of a healthy volunteer were performed to obtain the image data.The scanning data were imported into Mimics,Geomagic,and Solidworks software in turn.After registration and fusion,a 3D model of normal knee joint was established.On this basis,models of medial collateral ligament injury in different degrees of knee joint were simulated,which were divided into four groups,including:(1)medial collateral ligament was intact;(2)deep medial collateral ligament fracture;(3)superficial medial collateral ligament fracture;(4)complete rupture of medial collateral ligament.Finally,Ansys software was introduced to apply three modes of loads to the knee joint:(1)10 N·m valvaration torque was applied to the top of the femur.(2)A 4 N·m internal torque was applied to the top of the femur.(3)A 4 N·m external torque was applied to the top of the femur.The effects of four groups of models on knee biomechanics under different loads were analyzed. RESULTS AND CONCLUSION:(1)In the extension position of the knee joint,when a 10 N·m valgus torque was applied to the knee joint,the overall stress of the posterolateral meniscus increased with different degrees of medial collateral ligament injuries,while the stress of the articular cartilage did not change significantly.The peak stress of the posterolateral meniscus increased significantly with superficial medial collateral ligament rupture.(2)In the knee extension position,when a 4 N·m internal rotation torque was applied to the knee joint,the overall stress of the medial and lateral meniscus increased after different degrees of medial collateral ligament injury.When superficial medial collateral ligament rupture occurred,the peak stress of the meniscus shifted from the anterior horn of the medial meniscus to the anterior horn of the lateral meniscus.(3)In the knee extension position,applying a 4 N·m external rotation torque to the knee joint,the peak stress of the posterolateral meniscus increased more significantly than that of the medial meniscus,and the stress of the articular cartilage changed less.(4)These results show that the risk of meniscus injury secondary to superficial medial collateral ligament rupture is much higher than that of deep medial collateral ligament rupture when the knee is in extension,and the lateral meniscus is more vulnerable to injury than the medial meniscus.Both superficial medial collateral ligament and deep medial collateral ligament play an important role in the rotational stability of the knee joint.

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.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Objective To investigate the risk of hepatitis B virus (HBV) infection in the children born to HBV‐infected parent (s) after in vitro fertilization (IVF) .Methods From January 2008 to December 2013 , in the reproductive medicine center of the Third Affiliated Hospital of Zhengzhou University ,the medical history of 221 mothers by IVF were collected .Inclusion criteria were at least one of the parents was positive for hepatitis B surface antigen (HBsAg) ,and HBV DNA<1 × 104copies/mL . Hepatitis B vaccination status and HBV infection status of children were followed by telephone .Results One hundred and seventy‐two cases were followed up successfully ,and 49cases were lost .Two hundred and twenty‐four cases of children were HBsAg negative ,but one of them showed hepatitis B virus e antibody and hepatitis B virus core antibody positive .Conclusions The vertical transmission risk of HBV infection of children born to HBV‐positive patent(s) by IVF did not increase .

Adenocarcinoma, Follicular ; genetics ; Humans ; Mutation ; Thyroid Neoplasms ; genetics

Objective To observe expression and location of cannabinoid receptor 1 (CB1) in liver tissue of patients with chronic hepatitis B (CHB) ,and analyze the relationship of it with the liver fibrosis score,the serum levels of TGF-β1 and Leptin. Methods Liver biopsies were performed in 118 patients with CHB.The expression of CB1 in liver tissue was observed by immune histochemical staining, and semi-quantitative analysis was carried out to devide the CB1 score into four grades: -, +, + +, + + +. Serum levels of TGF-β1 and Leptin were determined by ABC-ELISA double-antibody sandwich method. Results The expression of CB1 in liver tissue with CHB had significant relationship with the fibrosis score. As the expression of the CB1 increased, the fibrosis score became higher ( F = 23. 369,P = 0. 000). Moreover, the expression of CB1 in liver tissue with CHB had significant relationship with the serum levels of TGF-β1 and Leptin( F values were 8. 762 and 5. 749;P values were 0. 001 and 0. 027, respectively). Conclusion CB1 may play promotive role in the process of hepatic fibrosis through regulation of TGF-β1 and Leptin.

Objective To explore the value of the diagnosis of middle cerebral artery (MCA) stenosis with transcranial Doppler ultrasound (TCD). Methods The clinical data in patients with ischemic cerebrovascular disease examined with digital subtract angiography (DSA)and TCD were analyzed retrospectively. DSA was used as a gold standard to analyze the sensitivity and specificity of the diagnosis of MCA stenosis with TCD. The normal and TCD blood flow velocity with different degrees of stenosis were compared. The best cut-off point of the TCD blood flow velocity of MCA at different degree of stenosis was calculated. Results DSA confirmed that 103 patients had MCA stenosis or occlusion, in which 12 were mild stenosis, 22 were moderate stenosis, 40 were severe stenosis, and 39 were occlusion. Compared to DSA, the sensitivity of TCD in detection of moderate and severe MCA stenosis or occlusion was 78. 8%, the specificity was 96. 0%, and the accuracy was 93. 0%, the missed diagnosis rate was 21. 2%, and the misdiagnosis rate was 4. 0%. As to the blood flow velocity, there was no significant difference between the mild stenosis and normal groups; while there was significant difference between the moderate stenosis and normal groups (P ＜0. 001). In addition, there was no significant difference in blood flow velocity between the moderate stenosis and severe stenosis groups. Determining the cut-off value of the best peak systolic velocity of the moderate stenosis was 163. 5 cm/s, while the best cut-off value of the mean velocity was 108. 5 cm/s. Conclusions TCD has certain advantages in the diagnosis of the MCA stenosis or occlusion, and it can be used as a safe and inexpensive screening means before DSA examination.

ObjectiveTo explore the methods and effectiveness of interventional revascularization of complex arteriosclerosis obliterans (ASO)of lower extremity arteries according to their imaging characteristics.Methods Seventy-eight patients with lower extremity ASO complex lesions classified as TASC Ⅱ C/D ( n =68 ) and TASC Ⅱ B ( n =10) underwent antigrade or combined antigrade-retrograde subintimal angioplasty.Their clinical situations were Fontaine stage Ⅲ/Ⅳ or severe stage Ⅱ.All the long occlusion,flush occlusion,multiple occlusion,popliteal artery occlusion,below knee artery occlusion and aortoiliac artery occlusion were identified as complex lesion imaging features and as the indication of interventional treatment if only there were visible outflow vessels and suitable puncture site.Statistical analysis was used to compare ankle-brachial index (ABI) pretreatment and post-treatment by t test.Results Successful revascularization was achieved in 73 patients technically.No obvious complications occurred.Ischemia symptoms improved quickly after accomplishment of recanalization.Average ABI increased from 0.45 ±0.07 to 0.76 ±0.11 after the treatment(t =- 19.78,P ＜0.01 ).Symptoms in 5 patients who failed to get arterial recanalization were stable.Follow up of 6 to 12 months in 47 patients showed stable improvement in 22 of them.Conclusion It is more practical to choose and expand application of interventional treatment for complex ASO according to imaging characteristics of lesions than according to TASC classification.

Objective To investigate the value of percutaneous transsplenic varices embolization (PTSVE) for treatment of upper gastrointestinal bleeding. Methods Twenty cases with liver cirrhosis and portal hypertension suffered upper gastrointestinal bleeding. PTSVE was administered to them with hardener and coils. Among them, 8 cases had massive hepatocellular carcinoma (HCC) in right lobe; 10 cases with hepatocellular carcinoma had portal vein tumor thrombus and occlusion; the other two cases with liver cirrhosis had portal vein thrombosis. All of these cases were not suitable for percutaneous transhepatic varices embolization (PTHVE) . PTSVE was performed under the guidance of fluoroscopy. Results Technical success was achieved in 18 patients. A total of 35 gastric coronary veins were embolized. In all these cases, upper gastrointestinal bleeding stopped after PTSVE. There was no recurrence within 1 month follow-up. No serious complication occurred. Conclusion PTSVE is a safe and efficient alternative treatment for upper gastrointestinal bleeding, especially for cases with portal vein occlusion or with massive HCC in right lobe of liver.