Objective    To introduce the surgical and perioperative strategy for giant mediastinal mass. Methods    The clinical data of 21 patients with giant mediastinal mass who underwent surgical treatment in Xinhua Hospital of Shanghai from January 2007 to July 2016 were retrospectively reviewed. There were 14 males and 7 females, with a mean age of 34.62 ± 22.95 years (range: 11 months to 79 years), and mean weight of 58.07±22.24 kg (range: 10.8 to 90.5 kg). Their clinical manifestation, anesthesia methods, surgical treatment and the prognosis were analyzed. Results    The tumor volume ranged from 8 cm×6 cm×6 cm to 25 cm×25 cm×8 cm. For surgical approach, 12 patients received median sternotomy, 5 anterior lateral incision, 1 posterior lateral incision, 2 "L"-shape sternotomy, 1 cervical and thoracic "]"-shape incision. All patients were given mass radical resection, except one patient with two-stage resection. Twelve patients needed other tissues resection besides the single tomor resection. The operation time was 55-480 (207.86±87.67) min, blood loss volume 700 (10-4 000) ml, intraoperative blood transfusion 800 (0-4 100) ml, postoperative mechanical ventilation time 4.75 (0-87) h, postoperative drainage time 3-12 (7.43±2.66) d, the total drainage volume 295-4 940 (1 584.76±1 173.98) ml, average daily drainage volume 62-494 (204.90±105.76) ml, and postoperative hospital stay 7-47 (11.86±8.51) d. The postoperative complications included pericardial effusion in 1 patient, Horner   syndrome in 1, left recurrent laryngeal nerve injury with the left phrenic nerve injury in 1, right phrenic nerve injury in 1 and delayed wound healing in 1. The remaining patients recovered well. All patients were followed up for 1 month to 9 years. Till September 1, 2016, 5 patients died and 2 suffered recurrent tumor. Conclusion    It is safe to perform surgical treatment after comprehensive evaluation of patients with giant mediastinal mass, perioperative mortality is low, and prognosis in patients with benign tumor is good.

OBJECTIVE： To investigate the effects of crystal form on in vivo and in vitro behavior of Astilbin nanosuspensions （AT-NS）. METHODS： AT-NS1 and AT-NS2 were prepared by precipitation method and miniaturized media milling method respectively. The particle size and polydispersity index （PDI） were determined by laser particle size analyzer. X-ray diffraction （XRD）， scanning electron microscopy （SEM）， HPLC and paddle method were used to analyze and compare the structure characteristics， appearance morphology and in vitro dissolution of AT raw material， AT-NS1 and AT-NS2. Totally 15 healthy male SD rats were randomly divided into AT raw material， AT-NS1 and AT-NS2 group， with 5 rats in each group. They were given relevant medicine suspension 120 mg/kg （using water as solvent） intragastrically； blood samples  were collected from orbit before medication （0 min） and 5， 10， 20， 30， 60， 120， 240， 480 min after medication. Using rutin as internal standard， HPLC method was used to determine plasma concentration of AT in rats. Pharmacokinetic parameters were calculated by using DAS 2.0 software and then compared. RESULTS： The particle sizes of AT-NS1 and AT-NS2 were （212.48±0.32） nm and （226.36±2.29） nm， respectively； PDI were 0.129 3±0.026 3 and 0.254 7±0.012 4. XRD analysis showed AT-NS1 was amorphous， and AT-NS2 was crystalline. Diffraction peaks of both were different from those of AT raw material. SEM analysis showed that AT-NS1 and AT-NS2 were similar in morphology， and they were spherical and uniform in size； AT raw material was lump with large particle size and different sizes. Results of dissolution tests showed that accumulative dissolution of AT raw material， AT-NS1 and AT-NS2 were 4.54％， 35.01％， 12.22％ at 1 h； accumulative dissolution of them were 24.01％， 81.14％， 64.69％ at 12 h； accumulative dissolution of them were 36.04％， 84.47％， 85.86％ at 24 h， respectively. Results of pharmacokinetic study showed， compared with AT raw material group， cmax and AUC0-∞ of AT-NS1 and AT-NS2 groups as well as t1/2z of AT-NS1 group were increased significantly， while tmax of AT-NS1 group was significantly reduced significantly （P＜0.05）. Compared with AT-NS2 goup， cmax， AUC0-∞ and t1/2z of AT-NS1 group were increased significantly， while tmax was reduced significantly （P＜0.05）. CONCLUSIONS： When AT is prepared into NS， dissolution in vitro and oral absorption in vivo of AT are increased significantly. In a short time， the dissolution/absorption of amorphous NS is faster than crystalline NS.

Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P < 0.05) and SNP analyses (FDR < 0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.
Adult ; Arachidonate 5-Lipoxygenase/genetics/*metabolism ; Benzene/toxicity ; Cell Count ; Cross-Sectional Studies ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Hematologic Diseases/chemically induced/genetics/*metabolism/pathology ; Humans ; Immunity, Innate/genetics ; Leukocytes/*drug effects/metabolism/pathology ; Male ; Occupational Exposure/adverse effects ; Peroxidase/genetics/*metabolism ; Polymorphism, Single Nucleotide ; Vascular Cell Adhesion Molecule-1/genetics/*metabolism

INTRODUCTIONThis study aims to evaluate the predictive factors affecting the clinical outcome of Below Knee Amputations (BKA) performed in diabetic foot patients admitted to National University Hospital (NUH) Multi-Disciplinary Diabetic Foot Team.

MATERIALS AND METHODSThis is a prospective cohort study of 151 patients admitted to the Department of Orthopaedic Surgery, NUH, for Diabetic Foot Problems (DFP) from January 2006 to January 2010. All had undergone BKA performed by NUH Multi-Disciplinary Diabetic Foot Team. Statistical analyses (univariate and multivariate analysis with logistic regression) were carried out using SPSS version 18.0, for factors such as demographic data, diabetic duration and control, clinical findings and investigations, indications for surgery, preoperative investigations and evaluation, microbiological cultures, and these were compared to the clinical outcome of the patient. A good clinical outcome is defined as one not requiring proximal re-amputation and whose stump healed well within 6 months. The ability to ambulate with successful use of a prosthesis after 1 year was documented. Statistical significance was set at P <0.050.

RESULTSMean age of study population was 55.2 years with a male to female ratio of about 3:2. Mean follow up duration was 36 months. Of BKAs, 73.5% gave a good outcome. Univariate analysis showed that smoking, previous limb surgery secondary to diabetes, high Total White Count (TW), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Urea, Creatinine (Cr), Neutrophils, absence of posterior tibial and popliteal pulses, low Ankle Brachial Index (ABI) and Toe Brachial Index (TBI) were associated with poor clinical outcome. Multivariate analysis showed that high CRP, ESR, Neutrophils, absence of popliteal pulse and low ABI were associated with poor clinical outcome. Of patients, 50.3% attained mobility with prosthesis after 1 year. Mortality rate was 21.2% within 6 months of operation, with sepsis being the most significant cause of death.

CONCLUSIONSuccess rate of BKA was 73.5%, with mortality rate being 21.2% within 6 months. In this cohort, 50.3% were able to attain eventual mobility with prosthesis after 1 year. Sepsis was the most significant cause of death. Markers of infection such as high CRP, ESR, neutrophils; and indicators of poor vascularity such as absence of popliteal pulse and low ABI were significantly associated with poor clinical outcome.

Adult ; Aged ; Aged, 80 and over ; Amputation ; methods ; Diabetic Foot ; surgery ; Female ; Humans ; Knee ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

Background: The use of translaminar screws may serve as a viable salvage method for complicated cases. To our understanding, the study of the feasibility of translaminar screw insertion in the actual entire subaxial cervical spine has not been carried out yet. The purpose of this study was to report the feasibility of translaminar screw insertion in the entire subaxial cervical spine. Methods: Eighteen cadaveric spines were harvested from C3 to C7 and 1-mm computed tomography (CT) scans and three-dimensional reconstructions were created to exclude any bony anomaly. Thirty anatomically intact segments were collected (C3, 2; C4, 3; C5, 3; C6, 8; and C7, 14), and randomly arranged. Twenty-one segments were physically separated at each vertebral level (group S), while 9 segments were not separated from the vertebral column and left in situ (group N–S). CT measurement of lamina thickness was done for both group S and group N–S, and manual measurement of various length and angle was done for group S only. Using the trajectory proposed by the previous studies, translaminar screws were placed at each level. Screw diameter was the same or 0.5 mm larger than the proposed diameter based on CT measurement. Post-insertion CT was performed. Cortical breakage was checked either visually or by CT. Results: When 1° and 2° screws of the same size were used, medial cortex breakage was found 13% and 33% of the time, respectively. C7 was relatively safer than the other levels. With larger-sized screws, medial cortex breakage was found in 47% and 46% of 1° and 2° screws, respectively. There were no facet injuries due to the screws in group N–S. Conclusions Translaminar screw insertion in the subaxial cervical spine is feasible only when the lamina is thick enough to avoid any breakage that could lead to further complications. The authors do not recommend inserting translaminar screws in the subaxial cervical spine except in some salvage cases in the presence of a thick lamina.

Tyrosine kinase inhibitors (TKI) significantly reduce the risk of recurrence and metastasis and prolong survival in patients with gastrointestinal stromal tumors (GIST), but drug resistance is often inevitable. Immunotherapy has been proven effective in multiple solid tumors, but the efficacy in GIST is unclear. The efficacy of immunotherapy depends on the tumor microenvironment (TME). Tumor-infiltrating immune cells and immune checkpoints are important components of TME, which not only participate in the regulation of tumor immune response but are also the key target of immunotherapy. A comprehensive analysis of them can clarify the mechanism of tumor immune escape. This review found that there are abundant tumor-infiltrating immune cells in GIST, which play an important role in tumor immune surveillance and escape. Although early clinical studies have shown that patients with GIST have a good tolerance to immunotherapy, the curative effect is not satisfactory. Therefore, how to select the responders of immunotherapy and coordinate the relationship between immunotherapy and TKIs is the key issue to be explored. At the same time, the gradual deepening of basic research and large sample prospective clinical trials will certainly provide more strategies for the application of immunotherapy in GIST.
Humans ; Gastrointestinal Stromal Tumors/drug therapy* ; Prospective Studies ; Immunotherapy/methods* ; Tumor Microenvironment ; Protein Kinase Inhibitors/pharmacology*

The process of globalization increases the risk of global transmission of infectious diseases, resulting in pressure for country's prevention and control of imported infectious disease. Based on the risk assessment of disease importation and local transmission, a strategy that conducting importation prevention and routine prevention and control before the importation of disease and taking emergency control measures after the importation of disease was developed. In addition, it is important to take part in global infectious disease response action, aid the countries with outbreak or epidemic to actively decrease the risk of disease importation.
Communicable Diseases ; Communicable Diseases, Imported/transmission* ; Disease Outbreaks/prevention & control* ; Epidemics ; Global Health ; Humans ; Risk Assessment ; Travel

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA. OBJECTIVE: ObjectiveThe trial aims to assess the effect and safety of CO laser moxibustion in patients with knee osteoarthritis compared with a sham control. METHODS: This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers. DISCUSSION CO laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.