0.05)between the two groups.Conclu- sion The long-term outcomes of e-CHB is not markedly different compared with that of e+CHB.

Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest and induce apoptosis of tumor cells. A series of novel tetrahydro-beta-carboline derivatives were synthesized as kinesin spindle protein inhibitor and evaluated as potential antitumor agents. All compounds showed promising KSP inhibitiory activity. Compounds 8 and 9 exhibited better antitumor activity (Lung/A549, Stomach/AGS) than CK0106023 with GI50/IC50 values (1.07/1.62 and 1.46/3.27 micromol x L(-1), 1.09/>10 and 1.22/6.33 micromol x L(-1), respectively).
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Carbolines ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Kinesin ; antagonists & inhibitors ; pharmacology ; Molecular Structure

Kinesin spindle protein (KSP/Eg5) is essential for the formation and maintenance of bipolar spindles during mitosis. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, a series of tetrahydro-beta-carboline derivatives 5a - k were synthesized as kinesin spindle protein inhibitor. Their structures were confirmed with 1H NMR, ESI-MS and elemental analysis. The synthesized compounds were evaluated for their inhibition of KSP.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Carbolines ; chemical synthesis ; chemistry ; pharmacology ; Kinesin ; antagonists & inhibitors ; metabolism ; Molecular Structure

OBJECTIVEThe explore the mechanism responsible for diaphragmatic contractile and relaxation dysfunction in a rat model of sepsis.

METHODSThirty-six adult male Sprague-Dawley rats were randomized equally into a sham-operated group and two model groups of sepsis induced by cecal ligation and puncture (CLP) for examination at 6 and 12 h following CLP (CLP-6 h and CLP-12 h groups). The parameters of diaphragm contractile and relaxation were measured, and the calcium uptake and release rates of the diaphragmatic sarcoendoplasmic reticulum (SR) and the protein expressions of SERCA1, SERCA2 and RyR in the diaphragmatic muscles were determined.

RESULTSThe half-relaxation time of the diaphragm was extended in both the CLP-6 h and CLP-12 h groups with significantly reduced maximum tension declinerate and the peek uptake rate of SERCA (P<0.01). Diaphragmatic maximum twitch force development rate, the maximal twitch, tetanus tensions and the peek release rate of SR decreased only at 12h after CLP (P<0.01). The expression levels of SERCA1 protein decreased significantly in the diaphragmatic muscles at 12h following CLP (P<0.01) while SERCA2 expression level and SERCA activity showed no significant changes.

CONCLUSIONIn the acute stage of sepsis, both the contractile and relaxation functions of the diaphragm are impaired. Diaphragmatic relaxation dysfunction may result from reduced calcium uptake in the SR and a decreased level of SERCA1 in the diaphragmatic muscles.

Animals ; Calcium ; metabolism ; Cecum ; Diaphragm ; drug effects ; metabolism ; Endoplasmic Reticulum ; metabolism ; Ligation ; Male ; Muscle Contraction ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Sepsis

OBJECTIVETo analyze and evaluate the acceptability of mifepristone compatible with misoprostone versus conventional surgical abortion among women under unwanted early pregnancy, so as to help the unexpected pregnant women to choose the satisfactory abortion, and to provide the evidence for clinicians to make a proper clinical decision.

METHODSSix medical databases were searched, including MEDLINE, EMBASE, Cochrane library, CBMdisc, CNKI and VIP, together with twelve journals hand-searched, and references of included studies additionally searched. Two qualified reviewers reviewed the original articles, evaluating qualities of articles, and extracting data independently. After heterogeneity test, the data was pooled using Revman software if capable, or descriptive analysis was applied.

RESULTSIn total, nine original clinical controlled trials were included, containing 3565 cases. Before abortion, more unwanted pregnant women chose the medical abortion because they believed medical abortion was less painful than surgical abortion (OR = 466.51, 95% CI: 91.37 - 2381.88), but medical abortion was less time-consuming than surgical abortion (OR = 0.02, 95% CI: 0.01 - 0.06). After abortion, satisfaction with medical abortion was similar to that with surgical abortion, with insignificant difference (P = 0.89). However, second choice and recommendation rates of medical abortion were much higher than those of surgical abortion with OR and 95% CI as 2.72, 2.13 - 3.47 and 4.19, 2.16 - 11.16, respectively.

CONCLUSIONSMedical abortion was less painful than surgical abortion and the rate of second choice and recommendation to others were all also higher than those of surgical abortion. However, the process of medical abortion was not as quick as surgical abortion but the satifacation of both methods seemed similar. Therefore, the two artificial abortion methods were not recommended to replace each other at the present time.

Abortifacient Agents ; adverse effects ; Abortion, Induced ; adverse effects ; methods ; Choice Behavior ; Controlled Clinical Trials as Topic ; Female ; Humans ; Mifepristone ; Misoprostol ; Pain ; etiology ; Patient Satisfaction ; statistics & numerical data ; Pregnancy ; Pregnancy, Unwanted

Objective: To investigate the clinical features and prognosis factors of acquired immunodeficiency syndrome (AIDS) patients complicated with cryptococcal meningitis (CM). Methods: Retrospective analyses were performed on clinical features, laboratory data, treatment status and related prognosis factors in 81 AIDS patients with CM admitted to the Department of Infectious Diseases, Beijing You′an Hospital, Capital Medical University from January 2010 to December 2017. The t test, rank sum test and χ² test were employed to analyze the data. Results: Of the 81 AIDS patients with CM, 71 cases were infected with human immunodeficiency virus (HIV) by sexual transmission (87.7%). The most common clinical symptoms were fever in 60 (74.1%), headache in 72 (88.9%), and nausea and vomiting in 56 (69.1%). Cerebrospinal fluid (CSF) examination results show that 60 cases (74.1%) had elevated opening pressure, the white blood cell count was 17.0 (6.0, 44.5)×10⁶/L, monocyte count was 9.0 (3.0, 29.5)×10⁶/L, the level of chloride was (117.26±5.61) mmol/L, of glucose was 2.89 (2.05, 3.41) mmol/L, of protein was 0.32 (0.21, 0.65) g/L, ink staining positive rate was 84.0% (68/81), fungal culture positive rate was 59.3% (48/81). The positive rate of serum cryptococcal antigen was 96.3% (78/81), and CSF cryptococcal antigen positive rate was 93.8% (76/81). The clinical efficacies were not significant different among different treatment regimens (χ²=1.479, P=0.533). After treatment, 60 patients survived and 21 died, with an overall mortality rate of 25.9%. Univariate analysis showed that consciousness disorder and CSF opening pressure were significantly higher in the death group than those in the survival group (χ²=22.365, t=0.317, respectively, both P<0.05), while serum albumin (Alb) and CD4⁺ T lymphocyte counts were significantly lower in the death group than those in the survival group (t=7.975, Z=-3.073, respectively, both P<0.05). Multivariate logistic regression analysis showed that consciousness disorder and Alb were independent factors influencing the clinical outcome of AIDS patients with CM. Consciousness disorder was related with poor outcome (odd ratio (OR)=26.704, P=0.011, 95% confidence interval (CI) 2.115-337.247), and higher Alb was related with good outcome (OR=0.671, P=0.005, 95%CI 0.507-0.888). The area under the receiver operating characteristic curve of serum Alb for predicting poor outcomes of AIDS patients with CM was 0.932 (95% CI 0.859-0.998, P<0.01). By using 31.7 g/L as cut-off value, the sensitivity was 95% and the specificity was 81% for predicting poor outcome. Conclusions AIDS complicated with CM has a high mortality rate, and its clinical features are lack of specificity. Consciousness disorder and Alb are independent prognosis factors.

OBJECTIVETo evaluate the use of acellular dermal matrix (ADM) to improve esthetic effects of alveolar ridge in dental implantology.

METHODSFifty patients with similar single missing tooth in the anterior maxilla were randomly divided into two groups: the ADM group was treated with dental implant therapy plus ADM transplantation; the control group was treated with dental implant therapy alone. The periodontal parameters and the changes of horizontal width of alveolar crest at implant zones were evaluated before surgery and 12 weeks after surgery.

RESULTSAll operated sites healed uneventfully. Mean horizontal width of alveolar crest in ADM group increased by (3.10 +/- 0.64) mm at 12 weeks and the control group increased by (0.30 +/- 0.50) mm, The volume increase showed a significant difference groups (P < 0.05). Mean horizontal width of alveolar crest in ADM group was (11.50 +/- 1.48) mm and the contralateral alveolar crest was (11.60 +/- 1.60) mm (P > 0.05).

CONCLUSIONSADM is a suitable material for the treatment of soft tissue deformities due to its biocompatibility and horizontal gain of soft tissue.

Adult ; Alveolar Bone Loss ; surgery ; Alveolar Ridge Augmentation ; methods ; Dental Implants, Single-Tooth ; Dermis ; cytology ; transplantation ; Extracellular Matrix ; transplantation ; Female ; Humans ; Male ; Skin, Artificial

BACKGROUNDThe neurogenic bladder dysfunction caused by spinal cord injury is difficult to treat clinically. The aim of this research was to establish an artificial bladder reflex arc in rats through abdominal reflex pathway above the level of spinal cord injury, reinnervate the neurogenic bladder and restore bladder micturition.

METHODSThe outcome was achieved by intradural microanastomosis of the right T13 ventral root to S2 ventral root with autogenous nerve grafting, leaving the right T13 dorsal root intact. Long-term function of the reflex arc was assessed from nerve electrophysiological data and intravesical pressure tests during 8 months postoperation. Horseradish peroxidase (HRP) tracing was performed to observe the effectiveness of the artificial reflex.

RESULTSSingle stimulus (3 mA, 0.3 ms pulses, 20 Hz, 5-second duration) on the right T13 dorsal root resulted in evoked action potentials, raised intravesical pressures and bladder smooth muscle, compound action potential recorded from the right vesical plexus before and after the spinal cord transaction injury between L5 and S4 segmental in 12 Sprague-Dawley rats. There were HRP labelled cells in T13 ventral horn on the experimental side and in the intermediolateral nucleus on both sides of the L6-S4 segments after HRP injection. There was no HRP labelled cell in T13 ventral horn on the control side.

CONCLUSIONUsing the surviving somatic reflex above the level of spinal cord injury to reconstruct the bladder autonomous reflex arc by intradural microanastomosis of ventral root with a segment of autologous nerve grafting is practical in rats and may have clinical applications for humans.

Anastomosis, Surgical ; Animals ; Atropine ; pharmacology ; Male ; Models, Theoretical ; Rats ; Rats, Sprague-Dawley ; Reflex, Abdominal ; drug effects ; physiology ; Trimethaphan ; pharmacology ; Urinary Bladder, Neurogenic ; physiopathology

OBJECTIVETo study the effects of deltamethrin (DM) on cell survival rate and intracellular Ca(2+) ([Ca(2+)]i) concentration in primary cultured astrocytes of rat.

METHODSThe cell survival rate was measured by Typan Blue assay; the intracellular [Ca(2+)]i concentration was determined by the fluorescent Ca(2+) indicator Fura-2/AM.

RESULTSThe survival rate of astrocytes was decreased to 91.9% after astrocytes were incubated with 1 x 10(-5) mol/L DM for 72 h (P < 0.05). The cell survival rates were 89.0%, 84.8%, 81.2% and 79.2% respectively when astrocytes were administered with 1 x 10(-4) mol/L DM for 4, 12, 24 and 72 h, which were remarkably lower than control groups (P < 0.01). Comparing with controls and before DM treatment, sharp increases in [Ca(2+)]i concentration [(451.4 +/- 42.3), (536.9 +/- 47.5) and (870.9 +/- 100.5) nmol/L respectively] were observed when astrocytes were incubated with 1 x 10(-7), 1 x 10(-6) and 1 x 10(-5) mol/L DM for 5 minutes (P < 0.01). After astrocytes were treated with 1 x 10(-8), 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) mol/L DM for 15 minutes, the [Ca(2+)]i concentrations were decreased to (124.3 +/- 6.0), (131.3 +/- 19.1), (118.9 +/- 1.4), (136.6 +/- 3.8) nmol/L respectively, which were significantly different from those of controls and before treatment. And this situation was almost keeping stable to 30 min.

CONCLUSIONThe cell survival rate was decreased and the [Ca(2+)]i concentration was temporarily increased when astrocytes were treated with DM.

Animals ; Astrocytes ; cytology ; drug effects ; metabolism ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Insecticides ; toxicity ; Nitriles ; Pyrethrins ; toxicity ; Rats

OBJECTIVETo explore the clinicopathological characteristics of primary thyroid-like follicular carcinoma of the kidney.

METHODSA case of primary thyroid-like follicular carcinoma of the kidney was studied with histology and immunohistochemical staining, and its clinical and pathological findings were further analyzed with review of the literature.

RESULTSThe patient was a 26-year-old asymptomatic woman who had a kidney mass during her annual physical examination. The tumor was well-circumscribed. Pathologically, the tumor showed follicular structures with colloid-like material in the lumina. Immunohistochemically, the tumor cells showed intense staining for CK7 and vimentin and negative for thyoid transcripation factor-1, thyroglobulin, thyoid peroxidase and RCC.

CONCLUSIONSThe diagnosis of primary thyroid-like follicular carcinoma of the kidney is based on the characteristic follicular architecture with colloid-like material, and the metastasis from a thyroid follicular carcinoma must be excluded clinically and pathologically before making the final diagnosis.

Adenocarcinoma, Follicular ; metabolism ; pathology ; Adult ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratin-7 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; Nephrectomy ; methods ; Neprilysin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; Transcription Factors ; Vimentin ; metabolism