AIMTo explore effects of intrathecal injection of U0126 on morphine withdrawal response and the spinal Phospho-CREB expression in morphine-induced withdrawal rats.

METHODSAll the rats were divided into 5 groups: control group, dependence group, withdrawal group, U0126 group (5 microg, it) and DMSO group. Morphine withdrawal score, touch evoked agitation scores(TEA score), immunohistochemical and Western-blotting technique were used to evaluate morphine withdrawal response and the expression of Phospho-CREB in the spinal cord.

RESULTSIntrathecal injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal symptoms. Morphine withdrawal scores in U0126 group (22.5 +/- 4.09) were significantly lower than that of withdrawal group (28.6 +/- 4.89, P < 0.05). TEA score of withdrawal group was 13.5 +/- 2.55, which was significantly higher than that of U0126 group (10.0 +/- 2.76, P < 0.05). Phospho-CREB positive neurons in the spinal dorsal horn of withdrawal group were 380 +/- 71, which is higher than that of U0126 group (293 +/- 47, P < 0.05). Compared with withdrawal group, level of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group was significantly lower.

CONCLUSIONMEK inhibitors U0126 could suppress expression of Phospho-CREB in the spinal cord.

Animals ; Butadienes ; pharmacology ; therapeutic use ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Injections, Spinal ; Male ; Morphine Dependence ; drug therapy ; metabolism ; Nitriles ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism ; Substance Withdrawal Syndrome ; drug therapy ; metabolism

The incidence of heterosexually transmitted HIV infection is rapidly increasing in China, which reached 44.7% among the HIV-positive patients in 2007. With a view to the reduction of HIV transmission and improvement of reproductive health in the Chinese population, this paper introduces the latest evidence obtained from the international epidemiological studies and randomized controlled clinical trials on the preventive effect of male circumcision (MC) on HIV transmission, and elucidates the cellular and molecular mechanisms of HIV transmission through the foreskin. Four studies published during 1997-2007 demonstrated that the mean prevalences of redundant prepuce and phimosis in 15,109 Chinese males aged 3-23 years in 4 areas of China were 43.90 and 11.55% , respectively, while the rate of MC was only 2.66%. As MC is a simple, inexpensive and highly effective technique in HIV prevention, we appeal to the policy-makers in China to conduct a practical program for promoting MC and enhancing male productive health in combination with other approaches to the prevention of HIV infection. MC for neonates, children, adolescents and adults should be included in the health insurance program, and free and timely MC should be performed for the male adults with the high risk of HIV infection and the normal ones whose wives are HIV-positive. Further investigations should be carried out on the epidemiology of redundant prepuce and phimosis, the acceptance and socio-cultural context of MC and the development of simpler and safer methods for MC.
Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Circumcision, Male ; HIV Infections ; epidemiology ; prevention & control ; Humans ; Male ; Reproductive Health Services ; statistics & numerical data

Purpose To investigate the frequency of anaplastic lymphoma kinase (ALK) expression in non-small cell lung cancer (NSCLC) patients and its correlation with the clinicopathologic features.Methods 1 047 cases of non-small cell lung cancer diagnosed by pathological examination were enrolled in this study.The status of ALK was detected by Ventana anti ALK reagent and IHC staining,and the clinical characteristics and pathological features of ALK gene were analyzed.Results Among 1 047 patients with non-small cell lung cancer,there are 72 cases with positive ALK (6.88％).These cases included 70 cases of adenocrcinoms and 2 adenosquamous carcinomas,with 40 males and 32 females,or 37 smokers and 35 non-smokers.The median age was 56 years and the mean age was 55.60 years.Histopathologically,43 cases were solid predominant adnocarcinomas,16 cases were acinar predominant adenocarcinomas,and 13 cases were papillary predominant adenocarcinomas.None were lepidic predominant adenocarcinomas.Conclusion ALK gene fusion lung cancer is a new molecular subtype of nonsmall cell lung cancer.It has unique clinical feature and pathological morphology.Ventana anti ALK reagent and IHC staining method are the first choice for the test of ALK positive non-small cell lung cancer,which has important significance to improve the detection rate and individual treatment for this type of lung cancer.

Objective:To prove the effect of double V-Y procedure for paramedian tubercles plasty in patients with thin lower lips and dissatisfied appearance of lower lips.Methods:From 2013 to 2019, 127 Chinese cases of thin and dissatisfied appearance of lower lips were included. A double V-Y procedure for paramedian tubercles plasty was performed. Objective data of lip morphology before and after operation were measured, and subjective satisfaction survey and long-term follow-up were conducted.Results:The midline lower red lip height, the height of paramedian tubercles of lower-lip and the protrusion of lower-lip were significantly higher than that before the operation. The time of apocatastasis, scar softening of incision, natural expression recovery and local numbness relief were evaluated by following up at 7 d, and 3-24 months after operation, and it showed 73.2% of subjective satisfaction. The time of detumescence was 6-32 (15.2±3.5) days; the time of incision scar softening was 2-10 (5.1±2.3) months; the time of expression recovery was 1-7 (3.1±0.9) months; the time of numbness disappearance was 5 d-2 years (158.2±82.6) days.Conclusions:The double V-Y advancement of vermilion mucosa flap procedure for paramedian tubercles plasty displays a significant effect in improving volume and shape of lower lips. It is recommended for further clinical application.

Objective:To observe and evaluate reductional M-shaped plasty method in patients with thick lips and dissatisfied lip appearance.Methods:From 2013 to 2019, 415 Chinese cases of thick upperlip without clear vermilion curve and tubercle were included. A reduction method for upper lip M-shaped plasty was performed. Objective data of lip morphology before and after operation were measured, and subjective satisfaction survey and long-term follow-up were conducted.Results:According to the statistics of 415 patients, the time of detumescence was 3-21 (11.8±2.6) days; the time of incision scar softening was 1-24 (2.6±0.8) months; the time of expression recovery was 1-24 (3.1±1.4) months; the time of numbness disappearance was 1-2 years. Three months after the operation, there was no significant change in the height of the central part of the upper red lip compared with that before the operation, the height of the red lip at the peak of the lip was significantly reduced, the height of the red lip was (13.3±2.2) mm before the operation, and (11.4±1.7) mm after the operation; the relative height of the dome point was significantly increased, the height was (0.4±1.0) mm before the operation, and the height was (2.1±0.5) mm after the operation. After more than 6 months of follow-up, patients' satisfaction rate of one operation was 72.0%, the satisfactory rate of upper lip shape was 75.4%, the long-term complications included obvious scars or discomfort (3.6%), local numbness (1.7%), and unnatural expression (0.7%).Conclusions:The reduction method for upper lip M-shaped plasty displays a significant effect in improving the shape of upper vermilion with thick and normal lips. The complications are slight and repairable. This lip cosmetology and rejuvenation procedure is recommended for further clinical application.

OBJECTIVEAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, while glucocorticoid (GC) is a critical component in multi-agent chemotherapy protocols currently used for the treatment of ALL. The purpose of this study was to investigate the relationship between the glucocorticoid induction test and the clinical features and the prognosis of Chinese childhood ALL.

METHODThe study recruited 309 hospitalized patients (187 male and 122 female) with childhood ALL, the sex, age, initial WBC count, immunophenotype, chromosome and gene expression were recorded. After diagnosis, all patients received GC induction test for 7 days. Then they were divided into prednisone good response (PGR) group and prednisone poor response (PPR) group according to the peripheral lymphoblast count on D8. Early responses to chemotherapy and treatment outcomes of the patients in the two groups were also analyzed.

RESULTOf the 309 patients, 263 belonged to PGR group and 46 belonged to PPR group. Initial WBC count was higher in PPR group than in PGR group (86.30×10(9)/L vs. 30.97×10(9)/L, P < 0.01) . B lineage ALL showed more sensitive to GC than T-ALL (86.6% vs. 60%, P < 0.05). Different initial-risk-group's sensitivity to GC differed from one another (high-risk:51.4%, medium-risk: 82.7%, standard risk: 93.7%, P < 0.0125). There was no significant difference between two groups in chromosomal karyotypes (P > 0.05). BCR-ABL positive ALL showed lower sensitivity to GC (P < 0.05) , while MLL, TEL-AML1, E2A-PBX1 positive rates in two groups were of no statistical significance (P > 0.05). Bone marrow was reviewed on D15 and D33, and the CR rates in PGR group were significantly higher than that in PPR group (D15: 60.5% vs. 32.6%, D33: 94.6% vs. 73.3%, P < 0.01) ; Minimal residual disease (MRD) levels were examined on D33, W12, and both were much lower in PGR group (D33: P < 0.01, W12: P < 0.05). Of the PGR group 215 patients (81.7%) remained continuously in complete remission (CCR) while only 28 cases (60.9%) in PPR group did so. The CCR rate was much higher in PGR group than that in PPR group (P < 0.01).

CONCLUSIONClosely related to clinical features and the outcomes of treatment, GC induction test is also an important prognostic factor in Chinese childhood ALL.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukocyte Count ; Male ; Neoplasm, Residual ; drug therapy ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; mortality ; Predictive Value of Tests ; Prognosis ; Remission Induction ; Survival Rate

OBJECTIVETo investigate the expressions of FOXC1 and matrix metalloproteinase 7 (MMP-7) in different molecular subtypes of breast cancer and their association with clinicopathological characteristics of the disease.

METHODSBased on immunohistochemical results of ER, PR, HER2, CK5/6, CK14 and EGFR, 105 breast cancer patients were classified as 4 subtypes: luminal, HER2 positive, basal-like subtype (BLs) and normal breast-like subtype (NBLs). The association of FOXC1 and MMP-7 expressions with clinicopathological parameters in different molecular subtypes was analyzed.

RESULTSOut of 105 patients with breast cancer, the subtypes of luminal, HER2 positive, BLs and NBLs accounted for 52.4% (55/105), 16.2% (17/105), 17.1%(18/105) and 14.3% (15/105), respectively. Patients with luminal and/or NBLs subtypes had significantly higher 5-year survival rate than those with HER2 positive and/or BLs did (log-rank=22.161, P<0.01). The overall positive expression rate of FOXC1 was 26.7% (28/105) and the expression was higher in BLs patients than that in other subgroups (χ²=30.108, P<0.01). The expression of FOXC1 was correlated with histological grade, tumor size, distant metastasis and 5-year survival rate of breast cancer. The overall positive expression rate of MMP-7 was 67.6% (71/105) and the expression of MMP-7 was also higher in BLs patients than that in other molecular subtypes (χ²=11.328, P<0.05). The positive expression of MMP-7 was correlated with metastasis in ipsilateral axillary lymph nodes, distant metastasis and 5-year survival rate of the patients. FOXC1 was correlated with MMP-7 (r=0.325, P<0.01).

CONCLUSIONPatients with luminal and/or NBLs breast cancer have more favorable prognosis than those with HER2 positive and/or BLs subtypes. The expressions of FOXC1 and MMP-7 are closely correlated with the clinicopathological features of breast cancer patients.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; diagnosis ; pathology ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Matrix Metalloproteinase 7 ; metabolism ; Middle Aged ; Prognosis

ObjectiveTo study the expression of human lysozyme-like protein 6 (LYZL6) in the male reproductive system and its physiological role.

METHODSThe recombinant P. pastoris strain was cultured and induced with methanol to express LYZL6, followed by purification using chitin affinity chromatography. The bactericidal activity of the recombinant LYZL6 was observed by bilayer agar plate diffusion assay, and then the recombinant protein was used as an immunogen to generate polyclonal antibodies, whose specificity was examined by ELISA. The distribution of LYZL6 in the human tissue and semen was identified by Western blotting and the subcellular localization in the testis was investigated by immunohistochemistry.

RESULTSAt pH 5.6, recombinant LYZL6 exhibited a high bacteriolytic activity against M. lysodeikticus. ELISA analysis showed that the anti-LYZL6 polyclonal antibodies could bind the recombinant protein with a high specificity. Western blot manifested the expression of LYZL6 in the testis and epididymis, higher in the former than in the latter. LYZL6 was also detected in the sperm protein extract, while protein bands were not observed in the seminal plasma. Immunodetection with a specific antiserum localized the LYZL6 protein in the late spermatocytes and round spermatids.

CONCLUSIONSLYZL6 has a higher bacteriolytic activity under low pH condition and is bound to spermatozoa after secreted in the testicular epithelia, suggesting that LYZL6 could act as a potential hydrolase for carbohydrates in zona pellucida penetration.

Blotting, Western ; Epididymis ; metabolism ; Humans ; Male ; Muramidase ; genetics ; metabolism ; Pichia ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Semen ; metabolism ; Spermatozoa ; metabolism ; Testis ; metabolism

Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Leukemia, Promyelocytic, Acute ; RNA, Long Noncoding ; Tretinoin

ObjectiveTo analyze the differential components in water extract of Chuanxiong Rhizoma before and after processing with wine， and to explore the molecular mechanism of Chuanxiong Rhizoma processed with wine in enhancing anti-cerebral ischemia injury. MethodUltra high performance liquid chromatography tandem quadrupole orbitrap high resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to qualitatively analyze the main chemical components in water extract of Chuanxiong Rhizoma based on the spectral information of compound， comparison of reference substance and references. The chemical pattern recognition method was used to screen the differential components of Chuanxiong Rhizoma before and after processing. Based on these differential components， the potential targets of differential components were predicted by online databases， and the related targets of cerebral ischemia were searched. Cytoscape 3.6.0 was used to establish the network diagram of differential components-action targets-diseases of Chuanxiong Rhizoma processed with wine. The protein-protein interaction （PPI） network of intersection targets was constructed by STRING 11.5. The potential targets of differential components against cerebral ischemia were analyzed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis through DAVID 6.8. At the same time， the chemical compounds with high relative content and increased peak area after wine processing were docked with their corresponding targets to verify the mechanism of enhanced effect after wine processing. ResultA total of 71 chemical components were identified from Chuanxiong Rhizoma， 34 differential components and 603 potential targets were screened out. At the same time， a total of 769 disease targets and 60 intersection targets were obtained. Seven key targets were identified through PPI network analysis， including JUN， signal transducer and activator of transcription 3 （STAT3）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-1β （IL-1β）， vascular endothelial growth factor A （VEGFA）， Caspase-3 （CASP3） and mtrix metalloproteinase 9 （MMP9）. Tumor necrosis factor （TNF） signaling pathway was the main differential signaling pathway. The results of molecular docking showed that differential components （senkyunolide K， senkyunolide F， 3-n-butylphthalide， Z，Z′-6，8′，7，3′-diligustilide， ferulic acid and Z-ligustilide） and corresponding targets had good binding activities. ConclusionThe synergistic mechanism of Chuanxiong Rhizoma processed with wine may be related to the enhanced inhibitory effect of inflammatory reaction.