[Recommendations for management of antiphospholipid syndrome in China].

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder with vascular, obstetric, and hematological manifestations associated with thrombotic and inflammatory mechanisms orchestrated by antiphospholipid (aPLs) antibodies. Current clinical practice in APS is highly variable duo to lack of high quality of evidence. Here, Chinese Rheumatology Association developed recommendations for management of APS in China. The recommendations cover the early diagnosis, disease evaluation, thrombotic risk assessment, and treatment.

[Feasibility on the diagnosis of non-calcified plaque based on radiomics of pericoronary adipose tissue on plain CT scan image].

Objective: To investigate the diagnostic value of radiomics model based on plain CT scan of peripheral coronary artery adipose tissue for non-calcified plaque. Methods: The image data of 461 patients undergoing coronary CT angiography (CCTA) in the Department of Radiology of the First Affiliated Hospital of Suzhou University from August 1,2019 to July 31,2020 were retrospectively analyzed. Two hundred and six cases (355 branches) with non-calcified plaques, and 255 cases (510 branches) with no coronary artery disease were detected by CCTA. The regions of interest (ROI) of the pericoronary adipose tissue were segmented on the plain CT scan images (coronary calcification score (CCS) sequence). The coronary ROI was determined by selecting the coronary artery with a length of 40 mm and starting at 10 mm from the opening of the coronary artery, and the pericoronary adipose ROI was generated automatically. The pericoronary fat attenuation index (FAI) was then performed, and the radiomics features were extracted. The 865 coronary arteries were divided into the training group (n=606) and the testing group (n=259) at a ratio of 7∶3, and the radiomics model was carried out. The receiver operating characteristic (ROC) analysis was used to assess the FAI value and the diagnostic efficacy of the radiomics model for non-calcified plaque. Results: A total of 1 692 features were extracted from images of pericoronary adipose based on plain scan. All features were screened by using max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), and 14 features were selected for the establishment of the radiomics model. The accuracy, sensitivity, specificity and area under the curve (AUC) of the model in distinguishing patients with non-calcified plaque and those without coronary stenosis in the testing group were 70.3%, 63.2%, 75.2% and 0.75, respectively. Conclusion: The radiomics model based on plain CT scan of the pericoronary adipose tissue had good diagnostic efficacy for non-calcified plaque.

[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

[Practice guideline for patients with osteoporosis].

In recent years, osteoporosis (OP) has become one of the main diseases affecting the health of middle-aged and elderly people in China, and the prevalence of OP has increased significantly. The clinical diagnosis and treatment guidelines for this disease are also constantly updated. The overall principles speciallyemphasise that doctors and patients need to work together to negotiate the details of the diagnosis and treatment guidelines, in order to improve the OP clinical diagnosis and treatment rate. Therefore, patients' knowledge of the disease, understanding of clinical guidelines, and cooperation with doctors to implement diagnosis and treatment plans are very important. In this study, from the most concerned issues of the patients, we established the OP patient practice guideline working group. 14 recommendations, as the OP patient practice guidelines, are proposed in accordance with the relevant principles of the "World Health Organization guidelines development manual" and the international normative process.

[The influence of patellofemoral joint degeneration on outcome of Oxford medial unicompartmental knee arthroplasty].

Objective: To explore the influence of lateral patellofemoral joint degeneration on the treatment of anteromedial osteoarthritis of knee joint by Oxford medial unicompartmental knee arthroplasty. Methods: The clinical data of 73 patients (73 knees) with knee osteoarthritis underwent unicompartmental knee arthroplasty at Department of Orthopaedic Surgery, Xuanwu Hospital, Capital Medical University from March 2016 to December 2017 were analysed respectively.There were 18 males and 55 females, aged (68.6±7.5) years(range: 53 to 89 years).The lateral patellofemoral joints of patients were evaluated by Ahlback grading system. Patients with Ahlback 0 andⅠ were in the non degenerative group (37 cases), and those with Ahlback Ⅱ and above were in the degenerative group (36 cases). Hospital for special surgery knee score(HSS) and the Western Ontario and McMaster Universities(WOMAC) osteoarthritis index, as well as the condition of kneeling, sit to stand movement, up stair and down stair were recorded. The data before and after operation were compared by paired sample t test, and the data between groups were compared by independent sample t test. χ(2) test was used for counting data. Pearson correlation analysis was used to compare the correlation between ahlback score, HSS and WOMAC osteoarthritis index. Results: The follow-up time was (35.1±6.6) months (range: 25 to 47 months).The knee function of the patients improved significantly after operation.The HSS score increased from 57.7±11.8 preoperative to 81.8±7.8 postoperative (t=16.64, P=0.00) and WOMAC osteoarthritis index decreased from 48.9±13.4 preoperative to 15.6±8.8 postoperative (t=20.48, P=0.00). There was no statistical difference in the change of HSS between the degenerative group and the non-degenerative group before and after surgery(27.5±12.2 vs. 22.5±12.3, t=-1.65, P=0.10) as well as the change of WOMAC osteoarthritis index(31.8±14.0 vs. 36.4±13.7, t=-1.35, P=0.18), but the lateral patellofemoral joint degeneration was related to inability to complete squats (χ(2)=5.17, P=0.04) and sitting up (χ(2)=7.22, P=0.01). Conclusion: The degeneration of lateral patellofemoral joint has no effect on the early functional recovery of patients with anteromedial knee osteoarthritis after Oxford medial unicompartmental knee arthroplasty.

[The study of making decision in the timing of delivery for patients of placenta previa through dynamic monitoring the length of cervical canal by perineal ultrasound].

Objective: To investigate the value of dynamic monitoring of cervical canal length by transperineal ultrasonography in the decision-making of the timing of delivery in patients with complete placenta previa, then to provide clinical guidance for complete termination of placenta. Methods: A total of 130 patients with complete placenta previa from 28 weeks to 30 weeks of gestation between January 2014 and October 2017 in Jiaxing Maternal and Child Health Hospital were selected. There were 66 patients in the experimental group and 64 in the control group, closely monitor the patient's vital signs, abdominal pain, abdominal distension, vaginal bleeding and fetal intrauterine conditions. In the experimental group, the length of the cervical canal was monitored by perineal ultrasonography at 2 hours and 12 hours after admission. This led to termination of the pregnancy. The control group was instructed to terminate the timing of pregnancy based on the patient's abdominal pain relief symptoms and vaginal bleeding. Compare the maternal and fetal outcomes of both groups. Results: The length of the cervical canal was (31.3±1.3) mm when the experimental group was admitted to the hospital, and the length of the cervical canal after the use of the retention drugs 2 h and 12 h was (32.1±0.4) mm and (32.2±0.4) mm, respectively.Compared with the length of the cervix at the time of admission. There was no significant change in the length of the cervical canal after the application of the retention drug 2 and 12 h(all P>0.05). The delivery week of 11 patients in the experimental group did not exceed 34 weeks, and 28 cases in the control group, and there was significant difference between the two groups. Compared with the control group, the difference of birth rate did not exceed 34 weeks, birth weight and hospitalization time decreased significantly (all P<0.05). However, there was no significant difference in maternal outcomes between the two groups. Conclusion: Through monitoring the length of the cervical canal by perineal ultrasound can make a better decision for the patients of complete placenta previa to chose the time of delivery.

[Analgesic effects of ionotropic glutamate receptor antagonists MK-801 and NBQX on collagen-induced arthritis rats].

OBJECTIVE: The ionotropic glutamate receptorantagonists include two types: MK-801, antagonist of N-methyl-D-asparticacid (NMDA) receptor, and NBQX, antagonist of non-NMDA receptor.The above-mentioned ionotropic antagonists can block the glutamate and its corresponding receptor binding to produce analgesic effect. The objective of this research was to study two antagonists in analgesic effect on rat behavior,as well as to investigate the down-regulation and up-regulation of cyclooxygenase-2 (COX-2) and Janus-activated kinase (Jak3) in collagen-induced arthritis (CIA) rat serum and tissue fluid after the application of these antagonists, that is, the effect on molecular biology. METHODS: This study used the ionotropic glutamate receptors as the target and established CIA rat model. Vivo studies were used to observe changes in behavior and molecular biology of the CIA rat.Behavioral assessment includedmechanical allodynia and joint swelling in the CIA rat,where themechanical allodynia was measured using the paw-withdrawal threshold (PWT) with VonFrey filaments according to the "Up-Down" method,and the drainage volume was used to assess joint swelling. Then the blood samples taken from the heart of the rat and the tissue homogenate were collected to detect the down-regulation and up-regulation of COX-2 and Jak3 in the serum and tissue fluid after the antagonists wereused. RESULTS: Using MK-801, NBQX alone or using the combination of these two antagonists,these three methods all could alleviate pain(P<0.01).The analgesic effect lasted more than 24 h.Both antagonists reached the peak of analgesia at the end of 4 hours post-injection. NBQX had stronger analgesic effect than MK-801 (P<0.05).Whether alone or combined use of these two antagonists,could not change the CIA rats' swelling of the joint (P>0.05). MK-801 could decrease the expression of COX-2 (P<0.01).At the same time, NBQX did not have this effect (P>0.05). Using MK-801, NBQX alone or combination of these two antagonists could not affect the increased expression of Jak3 caused by the CIA (P>0.05). CONCLUSION: MK-801 and NBQX could both alleviate pain, NBQX was much better than MK-801. Neither MK-801 nor NBQX had the effect on the swelling of the joint. NMDA receptor and COX-2 inflammatory pathways had certain interactions. For Jak3, it could not be found to have cross-function with ionotropic glutamate signaling pathways by this experiment.

[Analysis of early failure of the PHILOS in proximal humerus fractures].

OBJECTIVE: To analyze the reasons of early failure of the PHILOS in proximal humerus fractures. METHODS: From Nov. 2010 to Nov. 2014, there were 117 patients with humerus fractures treated with PHILOS locking plate in Department of Orthopaedics, Xuanwu Hospital. All of the patients were treated with the plate by open reduction internal fixation, and we analyzed these cases retrospectively. After the operation, we removed the drainage tube within 48 h, and the patients were allowed to do the passive motion 3 days after the surgery if the X-Ray showed the plate and screws were reliable. Eight cases failed within 4 weeks after the operation. We analyzed the reasons of the failure. RESULTS: The rate of the failed cases was 6.83%(8/117). The average age was 72.4(66-82) years. In the 8 failed cases, 3 were on the right side, and the other 5 on the left side. As for the reason of the fractures, 2 cases were because of car accidents, and the other 6 because of daily life injury. According to the Neer classification, 3 cases were 2-part fractures, and the other 5 3-part fractures. Three cases were total failure, and the other 5 partial failure. All the 8 failed cases failed within 4 weeks after the operation, of which 1 was on the sixth day after surgery, the other 7 2 to 4 weeks after the surgery.The 3 totally failed cases were treated by removing the screws and plates, the other 5 by conservative methods. All of the cases were malunion at the end. CONCLUSION: The early failure of the PHILOS locking plate in proximal humerus fractures is related to the bad reduction during the operation, the loss of medial cortex support, the limitation of screw length, the osteoporosis and the improper rehabilitation after operation.It is very important to do good preoperative plan for a surgeon. During the operation, we should try our best in the fracture reduction, use the appropriate plate and screws, and then pay attention to the rehabilitation after the operation. After all of this, the rate of failure may be decreased.

[Research of the effect of bone mineral density and fracture site of the vertebrae on low back pain in elderly patients with osteoporotic vertebral compression fractures].

OBJECTIVE: To investigate the effect of bone mineral density(BMD) and fracture site of the vertebrae on low back pain in elderly patients with osteoporotic vertebral compression fractures. METHODS: From August 2011 to August 2013, a total of 107 senile patients with osteoporotic vertebral compression fractures underwent percutaneous vertebroplasty were followed up for more than 2 ( average 2.5) years in Department of orthopedics, Xuanwu Hospital, Capital Medical University. The incidence of low back pain after vertebroplasty were analyzed on visual analog scale (VAS), and the relationship between BMD, vertebral fracture site were investigated. RESULTS: A total of 18 cases(16.8%)after vertebroplasty have significant low back pain. Along with BMD decreased [(-2.90±0.91) vs (-4.87±0.52)], the VAS of low back pain increasing, which showed statistical significance difference[(-3.12±0.91) vs (4.03±1.08), P<0.05]. The site of vertebral fracture was lower, the VAS was higher. CONCLUSIONS: About 16.8% patients show obvious low back pain after vertebroplasty. BMD and Vertebral fracture site were important factors of low back pain in elderly patients with osteoporotic vertebral compression fractures after vertebroplasty.

[Analysis of early failure of the PHILOS in proximal humerus fractures].

OBJECTIVE: To analyze the reasons of early failure of the PHILOS in proximal humerus fractures. METHODS: From Nov. 2010 to Nov. 2014, there were 117 patients with humerus fractures treated with PHILOS locking plate in Department of Orthopaedics, Xuanwu Hospital. All of the patients were treated with the plate by open reduction internal fixation, and we analyzed these cases retrospectively. After the operation, we removed the drainage tube within 48 h, and the patients were allowed to do the passive motion 3 days after the surgery if the X-Ray showed the plate and screws were reliable. Eight cases failed within 4 weeks after the operation. We analyzed the reasons of the failure. RESULTS: The rate of the failed cases was 6.83%(8/117). The average age was 72.4(66-82) years. In the 8 failed cases, 3 were on the right side, and the other 5 on the left side. As for the reason of the fractures, 2 cases were because of car accidents, and the other 6 because of daily life injury. According to the Neer classification, 3 cases were 2-part fractures, and the other 5 3-part fractures. Three cases were total failure, and the other 5 partial failure. All the 8 failed cases failed within 4 weeks after the operation, of which 1 was on the sixth day after surgery, the other 7 2 to 4 weeks after the surgery.The 3 totally failed cases were treated by removing the screws and plates, the other 5 by conservative methods. All of the cases were malunion at the end. CONCLUSION: The early failure of the PHILOS locking plate in proximal humerus fractures is related to the bad reduction during the operation, the loss of medial cortex support, the limitation of screw length, the osteoporosis and the improper rehabilitation after operation.It is very important to do good preoperative plan for a surgeon. During the operation, we should try our best in the fracture reduction, use the appropriate plate and screws, and then pay attention to the rehabilitation after the operation. After all of this, the rate of failure may be decreased.

Effects of artesunate and ursolic acid on hyperlipidemia and its complications in rabbit.

OBJECTIVE: To find the novel hypolipidemic agents, the effects of ursolic acid and artesunate on hyperlipidemia and its complications were determined in rabbit fed with Western-type diet. METHODS AND RESULTS: New Zealand rabbits fed a Western-type diet developed a hyperlipidemia. Rabbits received ursolic acid (25mg/kg) or artesunate (25mg/kg) alone, or in combination (12.5+12.5mg/kg), to prevent hyperlipidemia. Ursolic acid or artesunate alone significantly decreased the plasma cholesterol and triglyceride in rabbits. Furthermore, they both attenuated liver steatosis and reduced the area of aortic root lesions. The combination of ursolic acid and artesunate was more potent than either agent alone, which indicates a strong synergistic effect. CONCLUSION: The hypolipidemic effect of artesunate is firstly reported. Its combination with ursolic acid might have the potential to further develop for the treatment of atherosclerosis.

Methylenetetrahydrofolate reductase genotypes and haplotypes associated with susceptibility to colorectal cancer in an eastern Chinese Han population.

Methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, C677T and A1298C have been associated with several diseases, including cancer. We made a case-control study to analyze a possible association of MTHFR gene polymorphisms C677T and A1298C with risk for colorectal cancer in an eastern Chinese Han population of 137 patients with a confirmed histopathological diagnosis of CRC and 145 age- and gender-matched controls with no history of cancer. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The concentrations of folate in plasma were measured by chemiluminescence immunoassay. The MTHFR 677TT genotype had a protective effect against colorectal cancer, with an odds ratio (OR) = 0.467 (95% confidence interval (CI) = 0.225-0.966). The 1298CC genotype was significantly correlated with a reduced risk of colorectal cancer (OR = 0.192; 95%CI = 0.040-0.916). Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was 0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and 1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI = 0.044-0.654). MTHFR 677TT+CT genotypes had a significantly lower plasma folate concentration than those with the MTHFR 677CC genotype. MTHFR 1298AC+CC genotypes had a lower plasma folate concentration than those with the MTHFR 1298AA genotype (P < 0.05). In conclusion, subjects with the MTHFR 677TT and MTHFR 1298CC genotypes appeared to have a significantly lower risk for colorectal cancer. MTHFR haplotypes 677CC/1298CC and 677TT/1298AC were less common in cases than in controls. These haplotypes, when compared to the most common haplotype 677CC/1298AA, were associated with a decreased risk for colorectal cancer. We conclude that plasma folate level is influenced by MTHFR genotypes.

Non-peptide corticotropin-releasing hormone antagonists: syntheses and structure-activity relationships of 2-anilinopyrimidines and -triazines.

Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [125I]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (Ki = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than alpha-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH1 receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH1 receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH1 Ki = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines.

The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course.