Modified Posterior Short-Segment Pedicle Screw Instrumentation for Lumbar Burst Fractures with Incomplete Neurological Deficit.

PURPOSE: We have introduced a method of modified posterior short-segment pedicle screw fixation and evaluated its clinical effects in treating lumbar burst fractures with incomplete neurological deficits. METHODS: The data from 22 patients with lumbar burst fracture and incomplete neurological deficits who had undergone modified posterior short-segment instrumentation with Schanz screw fixation from January 2012 to February 2018 in our clinic were evaluated in the present retrospective study. All Schanz screws were implanted in an oblique downward direction into the vertebrae above and below the injured vertebra (insertion depth, 90%-100%). The implants were removed ∼1 year after surgery. Neurological function, back pain, anterior and posterior body height ratio, kyphosis angle, percentage of canal compromise, fracture severity, and treatment-related complications were evaluated. RESULTS: Technical success was achieved in all 22 patients. No infection, instrument loosening or failure, or breakage was observed. Statistically significant improvements with regard to the anterior body height (P < 0.05) and posterior body height (P < 0.05) ratios, kyphosis angle, and percentage of canal compromise (P < 0.05) were observed at 1 week postoperatively or the final follow-up visit. No correction loss had occurred at the final follow-up examination. Postoperatively, all patients with neurological deficits had functional improvement equivalent to ≥1 grade on the American Spinal Injury Association impairment scale and fracture union. Back pain was greatly improved postoperatively. CONCLUSIONS: Short-segment Schanz screw fixation implanted in an oblique downward direction seems to be a promising method for lumbar burst fractures with incomplete neurological deficits because it provided good clinical and radiographic outcomes.

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors.

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 µM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 µM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents.

Clinical characteristics and prognosis of primary Waldeyer's ring and lymph node diffuse large B-cell lymphoma in the rituximab era.

This study was to compare the clinical characteristics and prognosis of Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) and lymph node DLBCL (LN-DLBCL) in the rituximab era. Before propensity score-matched (PSM), WR-DLBCL group shows more favorable clinical characteristics than LN-DLBCL group. After PSM, there was no significant difference in the response rate and survivals between them. The 5-year PFS and OS rates were 65.0% and 78.6% for WR-DLBCL group, respectively, and 53.7% and 66.1% for LN-DLBCL group, respectively. In WR-DLBCL group, ECOG score, Ann Arbor stage, B symptoms and IPI were associated with poor PFS and OS. In LN-DLBCL group, ECOG score, Ann Arbor stage, LDH, and IPI were significant factors to PFS and OS. Multivariate analysis showed that Ann Arbor stage was the only significant factor to PFS for WR-DLBCL group, for LN-DLBCL group, Ann Arbor stage and IPI were independent factors to PFS, LDH was the only significant factor to OS. WR-DLBCL was associated with more favorable clinical characteristics compared with LN-DLBCL, whereas, WR involvement itself did not have a real favorable prognostic significance. The PFS and OS of DLBCL were largely dependent on other prognostic factors such as Ann Arbor stage, LDH or IPI.

Association between neutrophil-to-lymphocyte ratio and differentiated thyroid cancer: a meta-analysis.

The association between neutrophil-to-lymphocyte ratio (NLR) and differentiated thyroid cancer (DTC) is undecided. To rectify this question, we conducted a systematic meta-analysis based on 7 prospective cohort studies published between 2013 and 2015, comprising 7349 patients. Six of these cohorts included pretreatment (baseline) NLR data for patients with thyroid nodules. The meta-analysis of these 6 cohorts showed that the NLR of patients with DTC (4617 cases) was statistically similar to patients with benign nodules only (1666 cases), with a mean difference (MD) of 0.19 (95% CI: -0.09 to 0.46; I2 = 93%; P < 0.001). No significant difference in NLR was found between patients with DTC and patients with benign nodules. Two studies addressed an association between NLR and papillary thyroid carcinoma in patients stratified by age <45 and ≥45 years (496 and 891 cases, respectively); the pooled MD was 0.09 (95% CI: -0.37 to 0.55; I2 = 92.2%, P < 0.001). An elevated NLR seems not a reliable indicator of progressing DTC in patients with goiters, and there was no difference in NLR between patients aged <45 years and those aged ≥45 years. Well-designed and large-scale investigations are warranted to understand the value of NLR in the prognosis of DTC.

Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke.

Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

Oridonin suppress cell migration via regulation of nonmuscle myosin IIA.

Oridonin, which is isolated from Chinese herb Rabdosia rubescens (Hemsl.) Hara, has been implicated in regulation of tumor cell migration and invasion. In this study, treatment with oridonin enhanced the phosphorylation of myosin regulatory light chain (T18/S19) that regulates the ATPase activity of myosin IIA. Meanwhile, stress fibers were significantly more prominent after oridonin incubation, which impaired cell migration in transwell migration assays. All of these effects may be caused by the decreased interaction between myosin IIA and myosin phosphatase complex, but not kinases. Our data provide clear evidence of this novel pharmacological function for oridonin in treating cancer cell migration.

[Correlation of TLR2 and TLR4 gene polymorphisms with the susceptibility and recurrence of condyloma acuminatum].

OBJECTIVE: To explore the correlation of the gene polymorphisms of Toll-like receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma acuminatum (CA). METHODS: Using Snapshot, we detected the gene polymorphisms of TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and 1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative controls. We made comparisons between the CA patients and controls as well as between the cases of recurrent CA and those of non-recurrence at 6 months after treatment. RESULTS: There were 72, 48, and 20 cases of genotype TT, TC, and CC of TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3 cases in the controls. The gene frequency of mutant C was 31. 43% in the patients, significantly higher than 17.62% in the controls (χ2 = 12.04, P < 0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in the non-recurrent cases (χ2 = 4.16, P < 0.05). There were 74, 49, and 17 cases of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients, as compared with 73, 29, and 3 cases in the controls. The gene frequency of mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the controls (χ2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases, markedly higher than 25. 29% in the non-recurrent cases (χ2 = 4.18, P < 0.05). There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G), respectively, in the CA patients, as compared with 26, 58, and 21 cases in the controls. There was no significant difference in the gene frequencies of mutant G between the two groups (χ2 = 0.33, P > 0.05). No mutant genes of TLR2 2508 (G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2 597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93). CONCLUSION: TLR2 597(T/C) is tightly linked to 1350(T/C), which is correlated with both the susceptibility and the recurrence of condyloma acuminatum.

Pilomatrix carcinoma on the left side of the parotid region: A case report and review of the literature.

Pilomatrix carcinoma (PC) is a rare neoplasm, particularly in the parotid region. Thus, it is easily misdiagnosed and an optimal treatment regimen has not yet been established. The present study reports the case of a 43-year-old female who presented with a PC of the parotid region and reviews the associated published literature. The patient underwent three surgical excisions prior to the tumor being completely removed, and was misdiagnosed four times prior to the correct diagnosis. Once the tumor was completely removed, the patient received radiation therapy (RT). At the 2-year follow-up, the patient remained free of local recurrence and metastasis. To the best of our knowledge, only 3 cases of PC on the parotid region have been reported. Although an optimal treatment regimen has not been established, surgery with wide margins is recommended, with RT and chemotherapy producing mixed results.

Sesquiterpenes from the fruits of Illicium jiadifengpi and their anti-hepatitis B virus activities.

Two new compounds, 2S-hydroxyl-jiadifenolide (1) and jiadifenlactone acid (2), and eight known compounds were isolated from the fruits of Illicium jiadifengpi. Their structures were analysed using several spectroscopic techniques, including 1D-, 2D-NMR and HR-ESI-MS experiments. The anti-hepatitis B virus (HBV) activities of the isolates were evaluated via HBV transfection of the Hep G2.2.15 cell line. The inhibitory rates of the most active compounds, compounds 4 and 5, on the HBeAg and HBsAg expression were 28.85±3.15% and 17.53±1.81% and 37.93±2.74% and 23.47±9.52% at concentrations of 64.94µM and 61.35µM, respectively.

A new sesquiterpene lactone from the fruits of Illicium henryi.

AIM: To study the chemical constituents of the fruits of Illicium henryi. METHOD: Chromatographic separations on silica gel, Sephadex LH-20 gel and MCI gel were used to isolate the compounds. The structures were elucidated based on extensive spectroscopic data analyses. RESULTS: Seven compounds were obtained and their structures were identified as 10-benzoyl-cycloparvifloralone (1), cycloparvifloralone (2), 2α-hydroxycycloparviforalone (3), henrylactone B (4), merrillianone (5), henrylactone C (6) and 7, 14-ortholactone- 3-hydroxyfloridanolide (7). CONCLUSION: Compound 1 is a new sesquiterpene lactone. The tested compounds showed weak anti-HBV activities on HBV surface antigen (HBsAg) secretion and HBV e antigen (HBeAg) secretion using Hep G2.2.15 cell line.

Systematic evaluation on the use of acellular dermis matrix graft in prevention Frey syndrome after parotid neoplasm surgery.

OBJECTIVE: To study the effectiveness and safety of acellular dermal matrix (ADM) graft in preventing Frey syndrome after parotid neoplasm surgery, we reviewed foreign reported clinical randomized controlled trials systematically. Based on this review, we aimed to assess the effectiveness of ADM graft and provide reliable evidence for clinical application. METHODS: We reviewed foreign-language databases, such as MEDLINE, applied meta-analysis with Rev.Man 5, and drew forest plots with odds ratio as effect size. RESULTS: Three trials were recruited. The morbidity of Frey syndrome in experimental group was significantly lower than that in control on both subjective index and objective index, with odds ratios at 0.03 (95% confidence interval, 0.01-0.11) and 0.03 (95% confidence interval, 0.01-0.12), respectively. There was no significant difference between ADM group and blank control in total adverse reactions and complication incidence, whereas results differed for a kind of specific adverse reaction or complication. CONCLUSIONS: Based on existing research data, implanting ADM could effectively prevent Frey syndrome, and its poor prognosis effects did not significantly increase, which suggested that its total safety was reliable. Nevertheless, further investigations about the difference on a specific adverse reaction or complication were still needed.

[Impact on tyrosinase expression and export from endoplasmic reticulum by inhibition of 26S proteasome].

OBJECTIVE: To determine the impact on tyrosinase expression and export from endoplasmic reticulum by inhibition of 26S proteasome. METHODS: Western blot was used to detect 26S proteasome from 8 vitiligo patients and 4 healthy controls. Melanocytes were incubated with proteasome inhibitor (lactacystin) and further detected as follows: cell survival by MTT assay, proteasome activity with fluorescence, ultrastructure observation with electron microscope, co-localization of tyrosinase and calreticulin (endoplasmic reticulum marker) by confocal laser scanning microscopy and 26S proteasome and tyrosinase with Western blot. RESULTS: The 26S proteasome expression level from lesions of vitiligo (1.05 ± 0.40) was significantly lower than the donor sites (1.82 ± 0.88) and the healthy controls (1.88 ± 0.16) (P < 0.05). But no significant difference existed between the latter two groups (P > 0.05). Compared to the untreated group, a 12-h incubation of 10 µmol/L lactacystin showed inhibitory effects on melanocytes (0.999 ± 0.110 vs 1.372 ± 0.127, P < 0.05) and significantly decreased proteasome activity (0.234 ± 0.019 vs 1, P < 0.01). Expansion rate of endoplasmic reticulum in the lactacystin group (1.91 ± 0.17) was significantly higher than that of the untreated cells (1.17 ± 0.11) (P < 0.05). More tyrosinase co-localized with calreticulin in endoplasmic reticulum in lactacystin-treated cells was observed than that of the untreated group. Compared with the untreated group, significantly decreased levels of tyrosinase (146 ± 10 vs 269 ± 8, P < 0.01) and tyrosinase activity (0.159 ± 0.017 vs 0.221 ± 0.019, P < 0.01) were shown in the lactacystin group (P < 0.05). CONCLUSIONS: Significantly decrease of 26S proteasome is found in lesions of vitiligo patients. Inhibition of 26S proteasome may lead to expansion of endoplasmic reticulum of melanocytes, impact export of tyrosinase from melanocyte endoplasmic reticulum and expression of tyrosinase.

Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors.

Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure-activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented.

[Impact of treatment with low dose roxithromycin on stable bronchiectasis].

OBJECTIVE: To investigate the impact of treatment with low dose roxithromycin on clinical symptoms and CT scores in patients with stable bronchiectasis. METHODS: Fifty patients with bronchiectasis in stable condition were randomly assigned to a control group and a treatment group. Patients in the control group received ambroxol hydrochloride tablet 90 mg 3 times a day. Patients in the treatment group received roxithromycin disperse tablet 0.15 g every day and ambroxol hydrochloride tablet 90 mg 3 times a day. The course of treatment lasted for 6 months. Quality of life was assessed using St. George's respiratory questionnaire (SGRQ). The British Medical Research Council (MRC) dyspnea scale was used to assess the degree of dyspnea. The score for CT evaluation of the thorax, quality of life and SGRQ were performed for all patients before and after the treatment. RESULTS: After 6 months, the scores for quality of life (48 ± 13) were lower compared to that (58 ± 15) before treatment in the control group; however, the scores for bronchial wall thickening of bronchiectasis (1.8 ± 0.5) were higher than that (1.8 ± 0.4) before study. The scores for the extent of bronchiectasis (2.7 ± 1.6), the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) were reduced after treatment as compared to those before treatment [(4.8 ± 2.3), (1.8 ± 0.5), (9.5 ± 3.3)] in the treatment group, (all P < 0.01). The degree of dyspnea (1.3 ± 0.4) and quality of life (42 ± 12) were lower than those before treatment [(1.89 ± 0.45), (56 ± 15)] in the treatment group. Furthermore, the scores for extent of bronchiectasis (2.7 ± 1.6), the scores for the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) in the treatment group were significantly improved as compared with those [(4.8 ± 2.0), (1.8 ± 0.5), (9.7 ± 3.6)] in the control group respectively after treatment. At the same time, the degree of dyspnea (1.3 ± 0.4) in the treatment group was significantly improved as compared with that (1.7 ± 0.4) in the control group after treatment. CONCLUSIONS: The scores for the bronchial wall thickening of bronchiectasis were increased in patients with stable bronchiectasis. Low dose roxithromycin combined with ambroxol hydrochloride significantly improved degree of dyspnea, reduced scores for extent of bronchiectasis, scores for the bronchial wall thickening of bronchiectasis and the global CT score as compared to treatment with ambroxol hydrochloride alone in patients with bronchiectasis in stable condition.

Two new lignans and anti-HBV constituents from Illicium henryi.

Two new lignans, dihydrodehydrodiconiferyl alcohol 9-O-ß-D-(3″-O-acetyl)-xylopyranoside (1) and threo-4,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan 7-O-α-rhamnopyranoside (2) were isolated from Illicium henryi, together with ten known compounds, 3-12. Their structures were elucidated by extensive spectroscopic analyses. The anti-hepatitis B virus (anti-HBV) activity of compounds 1-12 inhibiting HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion on Hep G2.2.15 cell line was evaluated. (-)-Dihydrodehydrodiconiferyl alcohol (4) showed moderate inhibitory activity on both HBsAg and HBeAg secretion with IC(50) values of 0.06 and 0.53 mM, respectively.

Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors.

Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure-activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 <60 nM) with 180-fold selectivity over DYRK2. In addition, a moderately potent DYRK2 inhibitor (41, IC50 <400 nM) with a 5.4-fold selectivity over haspin was also identified.

Henrylactones A-E and anti-HBV constituents from Illicium henryi.

Five new sesquiterpene lactones, henrylactones A-E ( 1- 5), together with ten known compounds: cycloparvifloralone ( 6), tashironin ( 7), tashironin A ( 8), neoanisatin ( 9), anisatin ( 10), anislactone B ( 11), 7- O-acetylanislactone B ( 12), merrillianolide ( 13), cyclomerrillianolide ( 14) and pseudomajucin ( 15), were isolated from the stems and roots of ILLICIUM HENRYI. Their structures were elucidated based on extensive spectroscopic data analyses. Among them, henrylactone A ( 1) is a novel sesquiterpene with a dilactone moiety and its structure was confirmed by X-ray diffraction. Sesquiterpene lactones 1- 15 were tested for their anti-hepatitis B virus (HBV) activities. The most active compound, tashironin ( 7), exhibited an IC (50) value of 0.48 mM (SI = 6.3) inhibiting on HBV surface antigen (HBsAg) secretion and an IC (50) value of 0.15 mM (SI = 20.1) inhibiting on HBV e antigen (HBeAg) secretion using HBV transfected Hep G2.2.15 cell line.

Crystal structure of HsEg5 in complex with clinical candidate CK0238273 provides insight into inhibitory mechanism, potency, and specificity.

HsEg5 is an important mitotic kinesin responsible for bipolar spindle formation at early mitosis. A rich body of evidence shows that inhibition of HsEg5 can result in mitotic arrest followed by cellular apoptosis. Recently identified HsEg5 inhibitor, CK0238273, exhibits potent antitumor activity and is currently in clinical trial. Here we report the cocrystal structure of the motor domain of HsEg5 in complex with CK0238273 at a 2.15 A resolution. Compared to the previously published HsEg5-Monastrol complex structure, CK0238273 shares the same induced-fit pocket with similar allosteric inhibitory mechanism. However, CK0238273 shows better fitting to the binding pocket with 65% increase of hydrophobic interaction area than that of Monastrol. Some unique hydrophilic interactions were also observed mostly between the phenyl ring and 8-chloro on quinazolinone of CK0238273 with ARG221 and GLY217. We believe that the combination of these interactions defines the superior potency and specificity of CK0238273.