Objective To evaluate the accuracy and feasibility of primary total knee arthroplasty (TKA) assisted by the self-made extramedullary osteotomy template on distal femur alignment.Methods We retrospectively analyzed the clinical data of 40 patients with osteoarthritis or rheumatoid undergoing primary TKA from September 2015 to March 2016.All patients were divided into two groups,extramedullary group and intramedullary group.Extramedullary group had 20 patients (4 males and 16 females) aged 65.1±6.9 years (range 51-75).Intramedullary group had 20 patients (3 males and 17 females) aged 65.7±7.9 years (range 48-75).The blood loss volume,drainage in operation,postoperative range of motion (ROM) at 1 week and 2 weeks,deviation between the ideal value and preoperative hip-knee-ankle (HKA) angle,coronal and sagittal angle of the femoral prosthesis were compared within the two groups.Results The age,gender,body mass index,deviation between the ideal value and preoperative HKA angle,Hospital for Special Surgery (HSS) scoring system,ROM of knee were not significantly different between the two groups.The operation time was 97.4± 14.0 min in extramedullary group and 111.7±9.9 min in intramedullary group (P ＜ 0.05).The blood loss was 71.8± 14.0 ml in extramedullary group and 111.7± 10.0 ml in intramedullary group (P ＜ 0.05),while the drainage volume was 167.0±74.5 ml in extramedullary group and 243.2±91.6 ml in intramedullary group (P＜ 0.05).The postoperative mean deviation of the HKA angle in extramedullary group (2.37°±0.73°) was smaller than that in intramedullary group (3.26°±1.42°).Furthermore,the coronal alignment of the femoral prosthesis in extramedullary group (89.70°±1.91°) was larger than that in intramedullary group (87.69°±2.39°).The sagittal alignment of the femoral prosthesis in extramedullary group (90.03°±2.62°) was also significantly larger than that in intramedullary group (88.07°±2.43°,P ＜ 0.05).The postoperative ROM of knee at 1 and 2 week in the extramedullary group were 101.75°±7.48° and 114.00°±7.88° respectively,while those in the intramedullary group were 101.25°±8.41° and 114.25°±8.78°.There was no statistically different between the two groups.There was no intraoperative and postoperative early complications reported in the two groups.Conclusion Although the primary TKA assisted by the selfmade extramedullary osteotomy template on distal femur alignment can shorten operation time,decrease the blood loss and increase the accuracy of coronal and sagittal alignment,the HSS score and ROM of knee are similar as intramedullary method.

Objective To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in intrathoracic tuberculosis(TB).Methods We retrospectively analyzed patients underwent EBUS-TBNA with a final diagnosis of intrathoracic TB at Shanghai Chest Hospital from October 2009 to March 2013 and observed that the diagnostic efficacy by pathology and microbiology and safety of EBUS-TBNA for intrathoracic TB.Results 75 patients were diagnosed with pulmonary TB or intrathoracic tuberculous lymphadenitis,and accuracy was 80％ (60/75) by EBUS TBNA.A total of 60 patients had pathology,acid-fast bacilli(AFB) staining and mycobacterial culture test results,of whom 52 (86.67％)were diagnosed.Pathological findings were consistent with TB in 77.33％ patients (58/75),in 20.31％ (13/64) the smear were positive for AFB and in 46.67％ (28/60) were positive for cuhure.One hundred and twenty-nine mediastinal or hilar lymph nodes and 10 intrapulmonary lesions were biopsied in 75 patients,the average target number of per patient were 1.85.Pathological findings were consistent with TB in 66.19％ samples(92/139),in 13.91％ (16/115) were positive for AFB and in 38.32％ (41/107) were positive for culture.Multivariate regression revealed that short-axis diameter was an independent risk factor associated with positive pathology,smear and euhure.Additionally,more aspiration times cause higher pathology positive rate,pathology showing necrosis and positive smear were independent risk factors associated with positive cuhure.There were two patients occurred complications during operation.Conclusion EBUS-TBNA was a safe and effective method for the diagnosis of intrathoracic tuberculosis.

Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty-nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated.
Adult ; Aged ; Carcinoma, Hepatocellular/*genetics/pathology/surgery ; CpG Islands ; *DNA Methylation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Liver/pathology ; Liver Neoplasms/*genetics/pathology/surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*genetics ; Oligonucleotide Array Sequence Analysis ; Proportional Hazards Models ; RNA, Messenger/biosynthesis ; Transcriptome/genetics

Objective: To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN). Methods: A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People′s Hospital of Longhua District of Shenzhen were selected, and were divided into polycythemia vera (PV) group, essential thrombocyhemia (ET) group, and myelofibrosis (PMF) group according to their subtypes, with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides, the scores of the scale (myeloproliferative neoplasm symptom assessment form total symptom score, MPN-SAF-TSS) in different treatment periods (at the time of the visit, when the disease progressed, when the disease was stable, when the clinical improvement was made, when the partial remission was completed, at the time of remission and recurrence) were also compared. Results: At the time of initial diagnosis, there were significant differences in the incidences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ²=6.095, P=0.047), abdominal discomfort (χ²=7.342, P=0.025), poor mobility (χ²=13.029, P=0.001), inattention (χ²=6.099, P=0.047), pruritus (χ²=6.956, P=0.031), bone pain (χ²=7.807, P=0.020), fever (χ²=8.000, P=0.018) and weight loss (χ²=27.340, P<0.001). The incidences of poor mobility (85.71%, 24/28), inattention (67.86%, 19/28) and weight loss (82.14%, 23/28) in PMF group were significantly higher than those in PV group [42.86% (12/28), 39.29% (11/28), 35.71% (10/28)] and ET group [46.43% (13/28), 39.29% (11/28), 14.29% (4/28)] (all P<0.05). The incidences of abdominal discomfort (75.00%, 21/28) and bone pain (60.71%, 17/28) in PMF group were higher than those in PV group [39.29% (11/28), 25.00% (7/28)] (both P<0.05). The incidences of abdominal fullness (89.29%, 25/28) and fever (42.86%, 12/28) in PMF group were higher than those in ET group [60.71% (17/28), 10.71% (3/28)] (both P<0.05). The incidence of pruritus in PV group (71.43%, 20/28) was higher than that in ET group (42.86%, 12/28) and PMF group (39.29%, 11/28) (both P<0.05). Symptom load scores of patients with fatigue (χ²=368.594, P<0.001), abdominal fullness (χ²=261.312, P<0.001), abdominal discomfort (χ²=195.629, P<0.001), poor mobility (χ²=217.862, P<0.001), lack of concentration (χ²=280.664, P<0.001), night sweats (χ²=239.650, P<0.001), pruritus (χ²=254.418, P<0.001), bone pain (χ²=180.291, P<0.001), fever (χ²=231.613, P<0.001) and weight loss (χ²=227.831, P<0.001) were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P<0.05), and the symptom score of abdominal fullness was lower than that at the time of visit (P<0.05). Symptom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P<0.05). When the clinical improvement was made, symptom load scores of weakness, abdominal discomfort, inattention, night sweats, weight loss were lower than those when the disease was stable (all P<0.05). Symptom load scores of abdominal fullness, poor mobility, inattention, night sweats and pruritus in partial remission period decreased compared to temporary improvement period (all P<0.05). Compared to the partial remission period, the symptom load scores of weakness, abdominal fullness, night sweats, pruritus, bone pain and weight loss in complete remission period were lower (all P<0.05). At last, symptom load scores of weakness, abdominal fullness, abdominal discomfort, poor mobility, inattention, night sweats, pruritus, bone pain, fever and weight loss in recurrence period were higher than those in complete remission period (all P<0.05). Conclusion There are several differences in the main clinical symptoms among patients with different MPN subtypes, and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

Objective: To investigate the brain volume alterations in patients with hyposmia using voxel-based morphometry (VBM) and to correlate these alterations with the degree and duration of hyposmia. Methods: Forty patients with hyposmia from Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital since 2013 to 2016 and forty age and sex matched normal subjects were recruited in this study. Sniffin′ Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired T1-weighted magnetic resonance images from all subject on a 3T scanner. VBM was performed using VBM8 toolbox and SPM8 in a Matlab environment. Independent sample t test analysis was used to compare the volume of gray and white matter between the controls and patients. In addition, the Pearson or Spearman correlation analysis was used for the correlation between the voxel value of cerebral volume alterations area and the degree and duration of hyposmia on patients (threshold discrimination identification, TDI). Results: Compared with the controls, patients showed significantly decreased volume in the gray matter of right orbitofrontal cortex (number of voxel in clusters was 226, t=-4.46, P<0.001, uncorrected). There was negative correlation between decreased gray matter volume of the right orbitofrontal cortex with significantly decreased area and the TDI results (r=-0.40, P=0.01), but positive correlation with duration of hyposmia (r=0.37, P=0.02). Conclusions The patients with hyposmia show gray matter atrophy of the right orbitofrontal cortex. The duration may be an important risk factor for decreased gray matter in patients with hyposmia.

Objective: To investigate the white matter integrity in patients with olfactory dysfunction using diffusion tensor imaging (DTI). Methods: Twenty-one patients with olfactory dysfunction and sixteen age, sex and level of education matched normal subjects were recruited in this study. Sniffin′ Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with a echo planar imaging (EPI) sequence from all subjects on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral piriform cortex, orbitofrontal cortex, hippocampus and insula cortex adjacent white matter as well as capsula interna were delineated from the FA images as the region of interest associated with olfactory (ROI_awo) manually. Independent sample t test analysis was used to compare the FA value of all ROI_awo between the controls and patients. Results: In olfactory dysfunction group, the FA value of adjacent white matter of right piriform cortex and orbitofrontal cortex were significantly lower than those of control group (0.42±0.05 (±s) vs 0.45±0.05, 0.43±0.06 vs 0.49±0.07, t value was 2.32, 2.79, respectively, all P<0.05). The FA value of adjacent white matter of left piriform cortex and orbitofrontal cortex had no significant difference compared with those of control group (0.43±0.05 vs 0.45±0.04, 0.44±0.04 vs 0.47±0.06, t value was 1.65, 1.37, respectively, all P>0.05). The FA value of the adjacent white matter of bilateral hippocampus, insula cortex and capsula interna had no significant difference compared with those of control group, neither (0.45±0.08 vs 0.44±0.08, 0.45±0.09 vs 0.44±0.10, 0.41±0.08 vs 0.39±0.07, 0.41±0.07 vs 0.38±0.05, 0.64±0.08 vs 0.63±0.08, 0.64±0.07 vs 0.63±0.07, t value was 0.30, 0.15, 0.88, 1.34, 0.14, 0.35, respectively, all P>0.05). Conclusions The patients with olfactory dysfunction showed abnormal white matter connection in the major primary and secondary olfactory cortex. The reduced white matter integrity in ROI_awo might contribute to the pathogenesis of olfactory dysfunction.

Objective: Using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and microPET-CT to test the feasibility of ¹⁸F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of ¹⁸F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of ¹⁸F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat′s brain after PEA stimulation included bed nucleus and insula. Activation regions of rat′s brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat′s brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.

Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin′ Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ²=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.