Objective:To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.Methods:A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People's Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.Results:Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio ( OR) = 0.997, 95% confidence interval (95% CI) was 0.996-0.998], D-dimer ( OR = 0.960, 95% CI was 0.944-0.977), LDH ( OR = 0.998, 95% CI was 0.997-0.999) and TG ( OR = 0.706, 95% CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer ( OR = 1.001, 95% CI was 1.001-1.002), LDH ( OR = 1.004, 95% CI was 1.002-1.005) and D-dimer ( OR = 1.036, 95% CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients ( OR = 7.692, 95% CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95% CI was 0.866-0.973, P = 0.000]. Conclusions:Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

Although traditional treatment for Graves′ disease(GD) displays some effects, it is imperative to explore new treatment methods. Based on the pathogenesis of GD, biologic agents developed by consumption of B lymphocytes and acting on thyroid stimulating hormone receptor(TSHR), such as monoclonal antibodies, TSHR antagonists and epitopes, can provide more options for patients with GD, and some new drugs are expected to be put into clinical practice. By restoring the damaged immune system and maintaining normal thyroid function continuously, it can avoid the disadvantages of conventional therapies such as long-term treatment, induction or aggravation of Graves ophthalmopathy, permanent hypothyroidism, and other complications. Preliminary experience suggests that thermotherapy is effective and safe for patients with refractory GD. In addition, the traditional Chinese medicine improves the symptoms and thyroid function of GD patients.The emergence of new therapeutic modalities and techniques will provide new approaches for the future treatment of GD and help clinicians to make the best decision.

Objective:To establish and evaluate a predictive model for recurrence risk of Graves′ disease after antithyroid drugs(ATD) withdrawal.Methods:Among 308 patients with newly onset Graves′ disease taking ATD from 2012 to 2019, 170 patients who completed follow-up were enrolled and divided into relapse and remission groups according to whether hyperthyroidism reoccurred within 2 years after ATD withdrawal to establish the discovery cohort. An internal validation cohort was constructed by repeating the sampling with bootstrap. Cox regression analysis was used to screen risk factors and establish a predictive model, named Graves′ Recurrence Evaluation System(GRES). The differentiation and accuracy of GRES model were evaluated and compared with the GREAT score.Results:Of 170 patients, 90 Graves′ disease cases relapsed within 2 years after ATD withdrawal. According to Cox regression analysis, family history of Graves′ disease, younger age(<30 years), grade Ⅱ-Ⅲ goiter, high level of TRAb(≥13 IU/L), large thyroid volume(≥26.4 cm 3) and low 25(OH) D(<14.7 ng/mL) were included in the predictive model: PI=0.672×family history+ 0.405×age+ 0.491×severity of goiter+ 0.808×TRAb+ 1.423×thyroid volume+ 0.579×25(OH) D. PI≥1.449 was associated with a higher risk of recurrence after drug withdrawal. The GRES model has good prediction in assessing Graves′ disease relapse within 2 years after ATD withdrawal and better than GREAT score. Conclusion:GRES model can be used to evaluate the recurrence risk within 2 years for patients with newly onset Graves′ disease after ATD withdrawal, and facilitate clinicians to reasonably select treatment modalities in order to improve the remission rate.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To investigate the risk factors for recurrence of Graves′ disease after withdrawal of antithyroid drugs (ATD).Methods:This prospective study recruited 285 patients with newly onset Graves′ disease taking ATD from 2012 to 2018 at Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. A total of 121 patients who completed follow-up were enrolled and were divided into relapse and remission group according to whether hyperthyroidism reoccurred within 2 years after ATD with drawal. Demographics, clinical manifestations, thyroid serological characteristics, and thyroid color doppler ultrasound at baseline and withdrawal were compared between the two groups. Cox regression analysis was used to analyze the correlation between above factors and recurrence of Graves′ disease.Results:Sixty-five patients relapsed within 2 years after drug withdrawal. Patients with early recurrence were characterized by Graves′ disease genetic history and high baseline thyrotrophin receptor antibody (TRAb) levels. Family history, higher serum FT 3(≥18.1 pmol/L), FT 4(≥49.8 pmol/L), and TRAb(≥16.1 mIU/mL) levels, larger goiter(Ⅱ-Ⅲ) and thyroid volume(≥28.6 cm 3), higher peak velocity of superior thyroid artery (STA-PV; ≥0.6 m/s) before treatment, and higher TRAb(≥0.8 mIU/mL) level after ATD withdraw were risk factors for Graves′ disease recurrence. Higher 25-hydroxy vitamin D(≥14.7 ng/mL) level at baseline, as well as high level of TSH(1.4 μIU/mL) at withdrawal may reduce the risk of relapse. Conclusions:Family history of Graves′ disease, clinical manifestations, thyroid serological indicators and imaging characteristics of severe Graves′ disease before treatment all increased the risk of Graves′ disease recurrence. Patients with aforementioned factors should be actively evaluated in order to choose treatment modalities reasonably. We recommended to maintain lower TRAb titer within normal reference range and TSH level between 1.4 μIU/mL and upper limits of normal reference range at ATD withdrawal to reduce the recurrence rate of Graves′ disease.

Objective:To explore the significance of digital orthopedic technology in surgical plan for spinal tumor and the preliminary outcomes of 3D printed vertebral bodies in spinal tumor surgery.Methods:The clinical data of 2 patients were retrospectively analyzed who had had a 3D printed vertebral body implanted at Center of Orthopaedics, Shenzhen Hospital from June 2018 to December 2019. One was a 32-year-old male, diagnosed with cervical neurinoma; the other was a 27-year-old female, diagnosed with giant cell tumor of lumbar bone. 3D virtual reconstruction of tumor and surrounding structures was established via Mimics software for surgical plan. Virtual osteotomy was simulated, their disease models and guide templates were 3D printed, and their metal artificial vertebral bodies were 3D printed after personalized design of the vertebral body diameter, porosity and procedures of reconstruction and fixation. Lesion resection and prosthesis implantation were carried out in accordance with the preoperative plan. After operation, the motor function of cervical or lumbar vertebrae, tumor recurrence, and spinal stability reconstructed were regularly observed.Results:Resections and reconstructions went uneventfully in both cases. The 2 patients were followed up for 21 and 13 months respectively. Their postoperative images showed that their 3D printed vertebral bodies fitted the neighboring vertebral bodies well. The spinal stability was reconstructed without any loosening or periprosthetic osteolysis, and the tumors were removed completely with no recurrence in both cases. Their spinal motor function was satisfactory.Conclusions:Digital orthopedic technology can offer accurate guidance in the treatment of spinal tumors. It is necessary to consider local physiological anatomy in personalized design of a metal vertebral body 3D printed. Clinical application of 3D printed metal vertebral bodies is a new strategy for spinal reconstruction following spinal tumor resection.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective To evaluate the safety of Renaissance spine robot assisted system in spinal injury.Methods From March 2014 to May 2016,38 patients with spinal disease received spinal surgery assisted by spine robot system.They were 20 males and 18 females,with an average age of 42 years (range,from 12 to 69 years).There were 10 lumbar fractures,8 thoracic fractures and 20 spinal deformities.Pedicle screw implantation was conducted in 30 patients (PS group) and percutaneous vertebroplasty in 8 (PV group).One side was chosen randomly to use Mazor spine robot assisted system (assisted group) and the opposite side the conventional method (non-assisted group).The anteroposterior and lateral X-rays and CT scan of the lumbar and/or thoracic spine were performed in all patients after surgery.The precision of pedicle screws implantation in PS group was evaluated by the Abul-Kasimhierarchy grading system;location of the puncture trajectory,time used for puncture and radiation exposure time in PV group were evaluated.Results 208 pedicle screws were implanted in PS group,including 120 lumbar ones and 88 thoracic ones.For lumbar pedicle screw implantation,the excellent to good rate was 95.0％ (57/60) in the assisted group,significantly higher than that in the non-assisted group (80.0％,48/60) (P ＜ 0.05).For thoracic pedicle screw implantation,the excellent to good rate was 95.5％ (42/44) in the assisted group,significantly higher than that in the non-assisted group (77.3％,34/44) (P ＜ 0.05).There were 24 puncture trajectories in 8 patients in PV group,showing no pedicle penetration or cement leaking in any case.The mean time used for puncture was 5.5 ± 1.4 min in the assisted group,significantly shorter than that in the non-assisted group (17.8 ± 7.5 min) (P ＜ 0.05);the X-ray exposure time was 14.0 ± 4.0 s in the assisted group,significantly shorter than that in the non-assisted group (22.4 ± 6.0 s) (P ＜ 0.05).Conclusions Renaissance spine robot-assisted system deserves more clinical application,because in spinal surgery it can make pedicle screw implantation more precise and safer,and can reduce operation time and X-ray exposure time in percutaneous vertebroplasty.

A method for simultaneous determination of 25 kinds of fungicides in cereals, vegetables and fruits using SPE-LC-Q-TOF/MS technique was developed.The samples were extracted with acetonitrile containing 1% (V/V) acetic acid, purified by solid phase extraction (SPE) with a Crabon/NH2 cartridge, eluted with acetonitrile-toluene(3∶1, V/V), separated by a reversed phase C18 column, gradiently eluted with acetonitrile and 0.1% formic acid solution (Containing 5 mmol/L ammonium acetate), determined by LC-Q-TOF/MS, and quantified by external standard method.A data base of the accurate mass numbers and a library which contains 25 kinds of fungicides were established.The automatic retrieval of detection results was carried on according to the characteristics of the compound, such as accurate mass, retention time, isotope peak distribution, isotopic ratios, and so on.Based on the above results, the qualitative identifications of the 25 new fungicides were accomplished without the contrast of standard substances.The results indicated that 25 fungicides showed good linearity in the range of 0.02-200 μg/L, and the limits of detection (LOD) and the limits of quantification (LOQ) were 0.01-5.00 μg/kg and 0.02-20.00 μg/kg, respectively.The linear relative coefficients were greater than 0.995.The recoveries were in the range 71.8%-114.0% and the relative standard deviations (RSD) were ranged from 0.1% to 21.3% (n=3).The method has some advantages such as simplicity, rapidity and high sensitivity, and is suitable for the rapid determination of the common fungicides in cereals, vegetables and fruits.