Survival after minimally invasive radical hysterectomy with protective colpotomy for early-stage cervical cancer: A systematic review and meta-analysis.

Minimally invasive surgery on treatment of early-stage cervical cancer is debatable. Traditional approaches of colpotomy are considered responsible for an inferior oncological outcome. Evidence on whether protective colpotomy could optimize minimally invasive technique and improve prognoses of women with early-stage cervical cancer remains limited. We produced a systematic review and meta-analysis to compare oncological outcomes of the patients treated by minimally invasive radical hysterectomy with protective colpotomy to those treated by open surgery according to existing literature. We explored PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2022. Inclusion criteria were: (1) randomized controlled trials or observational studies published in English, (2) studies comparing minimally invasive radical hysterectomy with protective colpotomy to abdominal radical hysterectomy in early-stage cervical cancer, and (3) studies comparing survival outcomes. Two reviewers performed the screening, data extraction, and quality assessment independently. A total of 8 retrospective cohort studies with 2020 women were included in the study, 821 of whom were in the minimally invasive surgery group, and 1199 of whom were in the open surgery group. The recurrence-free survival and overall survival in the minimally invasive surgery group were both similar to that in the open surgery group (pooled hazard ratio, 0.88 and 0.78, respectively; 95% confidence interval, 0.56-1.38 and 0.42-1.44, respectively). Minimally invasive radical hysterectomy with protective colpotomy on treatment of early-stage cervical cancer had similar recurrence-free survival and overall survival compared to abdominal radical hysterectomy. Protective colpotomy could be a guaranteed approach to modifying minimally invasive technique.

Advanced Ag nanoparticles for the catalyzation of glyoxylic acid oxidation in through-holes electroless copper metallization.

Advanced Ag nanoparticles (Ag NPs) were prepared by wet chemical oxidation-reduction method, using mainly the tannic acid as reducing agent and carboxymethylcellulose sodium as stabilizer. The prepared Ag NPs uniformly disperse and are stable for more than one month without agglomeration. The studies of transmission electron microscopy (TEM) and ultraviolet-visible (UV-vis) absorption spectroscopy indicate that the Ag NPs are in homogeneous sphere with only 4.4 nm average size and narrow particle size distribution. Electrochemical measurements reveal that the Ag NPs behave excellent catalytic activity for electroless copper plating using glyoxylic acid as reducing agent. In situ fourier transform infrared (in situ FTIR) spectroscopic analysis combined with density functional theory (DFT) calculation illustrate that the molecular oxidation of glyoxylic acid catalyzed by Ag NPs is as the following routes: glyoxylic acid molecule first is adsorbed on Ag atoms with carboxyl oxygen terminal, then hydrolyzed to diol anionic intermediate, and last oxidized to oxalic acid. Time-resolved in situ FTIR spectroscopy further reveals the real-time reactions of electroless copper plating as follows: glyoxylic acid is continuously oxidized to oxalic acid and releases electrons at the active catalyzing spots of Ag NPs, and Cu(II) coordination ions are in situ reduced by the electrons. Based on the excellent catalytic activity, the advanced Ag NPs can replace the expensive Pd colloids catalyst and successfully apply in through-holes metallization of printed circuit board (PCB) by electroless copper plating.

Adsorption-Catalysis-Conversion of Polysulfides in Sandwiched Ultrathin Ni(OH)2 -PANI for Stable Lithium-Sulfur Batteries.

Strong adsorption and catalysis for lithium polysulfides (LiPSs) are critical toward the electrochemical stability of Li-S batteries. Herein, a hollow sandwiched nanoparticle is put forward to enhance the adsorption-catalysis-conversion dynamic of sulfur species. The outer ultrathin Ni(OH)2 nanosheets not only confine LiPSs via both physical encapsulation and chemical adsorption, but also promote redox kinetics and accelerate the conversion of sulfur species, which is revealed by experiments and theoretical calculations. Meanwhile, the inner hollow polyaniline soft core provides a strong chemical bonding to LiPSs after vulcanization, which can chemically adsorpt LiPSs, and synergistically confine the shuttle effect. Moreover, the Ni(OH)2 nanosheets with a large specific area can enhance the wettability of electrolyte, and the flexible hollow sandwiched structure can accommodate the volume expansion, promoting sulfur utilization and structural stability. The obtained cathode exhibits excellent electrochemical performance with an initial discharge capacity of 1173 mAh g-1 and a small capacity decay of 0.08% per cycle even after 500 cycles at 0.2 C, among the best results of Ni(OH)2 -based materials for Li-S batteries. It is believed that the combination of adsorption-catalysis-conversion will shed a light on the development of cathode materials for stable Li-S batteries.

Safety observation study on haemophilus influenza type B conjugate vaccines injected at different sites in Chinese infants.

In the present study, the safety of Haemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Immunogenicity and safety of three 2010-2011 seasonal trivalent influenza vaccines in Chinese toddlers, children and older adults: a double-blind and randomized trial.

The 2009 influenza A(H1N1) pandemic strain was for the first time included in the 2010-2011 seasonal trivalent influenza vaccine (TIV). We conducted a double-blind, randomized trial in Chinese population to assess the immunogenicity and safety of the 2010-2011 TIV manufactured by GlaxoSmithKline and compared it with the counterpart vaccines manufactured by Sanofi Pasteur and Sinovac Biotech. Healthy toddlers (6-36 mo), children (6-12 y) and older adults (≥60 y) with 300 participants in each age group were enrolled to randomly receive two doses (toddlers, 28 d apart) or one dose (children and older adults). The immunogenicity was assessed by hemagglutination-inhibition (HI) assay. The solicited injection-site and systemic adverse events (AEs) were collected within 7 d after vaccination. All the three TIVs were well-tolerated with 15.1% of participants reporting AEs, most of which were mild. No serious AEs and unusual AEs were reported. Fever and pain were the most common systemic and injection-site AEs, respectively. The three TIVs showed good immunogenicity. The seroprotection rates against both H1N1 and H3N2 strains were more than 87% in toddlers after two doses and more than 95% in children and more than 86% in older adults after one dose. The seroprotection rates against B strain were 68-71% in toddlers after two doses, 70-74% in children and 69-72% in older adults after one dose. In conclusion, the three 2010-2011 TIVs had good immunogenicity and safety in Chinese toddlers, children and older adults and were generally comparable in immunogenicity and reactogenicity.

12-Di-methyl-amino-2,2-di-fluoro-8-phenyl-1λ(5),3-di-aza-2λ(4)-boratri-cyclo-[7.3.0.0(3,7)]dodeca-1(12),4,6,8,10-pentaen-1-ylium.

In the title boron-dipyrromethene derivative, C17H16BF2N3, the benzene ring and the boron-dipyrromethene mean plane form a dihedral angle of 55.82 (8)°. In the crystal, pairs of C-H⋯F inter-actions link the mol-ecules, forming inversion dimers. Further C-H⋯F inter-actions link the dimers into a three-dimensional network.

{[(1Z)-3-Chloro-1H-isoindol-1-yl-idene]meth-yl}dimethyl-amine.

The asymmetric unit of the title compound, C11H11ClN2, contains two almost-planar independent mol-ecules: the isoindole and dimethyl-amino-methyl-ene mean planes in the two mol-ecules form dihedral angles of 5.45 (8) and 1.34 (8)°. The crystal packing exhibits no short inter-molecular contacts, except for a relatively short Cl⋯Cl distance of 3.4907 (7) Å.

Co-expressions of casein kinase 2 (CK2) subunits restore the down-regulation of tubulin levels and disruption of microtubule structures caused by PrP mutants.

CK2 shows disease-associated alteration in the scrapie experimental rodents and human prion diseases. In this study, mammalian expressing plasmids for human CK2 subunits, CK2α and CK2ß, were generated. Immunoprecipitation assays revealed stronger signals of PrP-CK2α complexes in the HEK293 cells co-transfected with plasmids expressing CK2α and various PrP constructs, including PG5, CytoPrP, PG9, and PG12. Meanwhile, obviously weaker signals of PrP-CK2ß complexes were also observed in the cells co-expressing CK2ß and PrPs. Tubulin-specific Western blots and immunofluorescence assays revealed that similar as the observations in the presences of PrP-specific siRNA, the abnormal PrPs-induced reductions of tubulin and disruptions of microtubule structures were completely restored in the cells when co-expressing CK2α and CK2ß. Moreover, co-expressions of CK2α and PrPs induced phosphorylation on p53 at the position of serine 6 (p53-Ser6), although much weaker than that in the cells expressing CK2α and CK2ß, while expressions of either PrPs or CK2 subunits did not change the cellular p53 level or induce phosphorylation on p53 at Ser9. Our data here verify again the molecular interaction between CK2 and PrP. Co-presences of CK2 subunits restore the down-regulated tubulin and disrupted microtubule structures caused by expressions of the abnormal PrP proteins in HEK293 cells.

Molecular interaction of TPPP with PrP antagonized the CytoPrP-induced disruption of microtubule structures and cytotoxicity.

BACKGROUND: Tubulin polymerization promoting protein/p25 (TPPP/p25), known as a microtubule-associated protein (MAP), is a brain-specific unstructured protein with a physiological function of stabilizing cellular microtubular ultrastructures. Whether TPPP involves in the normal functions of PrP or the pathogenesis of prion disease remains unknown. Here, we proposed the data that TPPP formed molecular complex with PrP. We also investigated its influence on the aggregation of PrP and fibrillization of PrP106-126 in vitro, its antagonization against the disruption of microtubule structures and cytotoxicity of cytosolic PrP in cells, and its alternation in the brains of scrapie-infected experimental hamsters. METHODOLOGY/PRINCIPAL FINDINGS: Using pull-down and immunoprecipitation assays, distinct molecular interaction between TPPP and PrP were identified and the segment of TPPP spanning residues 100-219 and the segment of PrP spanning residues 106-126 were mapped as the regions responsible for protein interaction. Sedimentation experiments found that TPPP increased the aggregation of full-length recombinant PrP (PrP23-231) in vitro. Transmission electron microscopy and Thioflavin T (ThT) assays showed that TPPP enhanced fibril formation of synthetic peptide PrP106-126 in vitro. Expression of TPPP in the cultured cells did not obviously change the microtubule networks observed by a tubulin-specific immunofluorescent assay and cell growth features measured by CCK8 tests, but significantly antagonized the disruption of microtubule structures and rescued the cytotoxicity caused by the accumulation of cytosolic PrP (CytoPrP). Furthermore, Western blots identified that the levels of the endogenous TPPP in the brains of scrapie-infected experimental hamsters were significantly reduced. CONCLUSION/SIGNIFICANCE: Those data highlight TPPP may work as a protective factor for cells against the damage effects of the accumulation of abnormal forms of PrPs, besides its function as an agent for dynamic stabilization of microtubular ultrastructures.

Knockdown of prion protein (PrP) by RNA interference weakens the protective activity of wild-type PrP against copper ion and antagonizes the cytotoxicity of fCJD-associated PrP mutants in cultured cells.

Development of the pathogenesis of transmissible spongiform encephalopathies (TSEs) requires the presence of both the normal host prion protein (PrPC) and the abnormal pathological proteinase-K resistant isoform (PrPSc). Reduction of PrPC levels has been shown to extend survival time after prion infection. In this report, based on analysis of the known sequences of human PrP, we constructed two small interfering RNA (siRNA) duplexes targeting the segments of amino acids (aa) 108-114 (Ri2) and aa 171-177 (Ri3). Western blot analysis results revealed that these PrP-specific siRNAs could effectively knock down the levels of either endogenous PrP in human neuroblastoma SHSY-5Y cells or recombinant PrP transfected with the plasmid expressing the full-length human PrP in human embryonic kidney (HEK) 293T cells. Meanwhile, the two siRNAs also showed a significant effect on the reduction of the expression of the PrP-PG9 and PrP-PG12 familial Creutzfeldt-Jakob disease (CJD)-associated PrP mutants with four and seven extra octarepeats, in the cells transfected with the respective expression plasmids. MTT tests identified that knockdown of wild-type PrP by Ri2 and Ri3 did not change the cell growth capacities, but significantly decreased the cell resistances against the challenge of Cu2+. Co-expression of Ri2 and Ri3 partially antagonized the cytotoxicity caused by expressing PrP-PG9 and PrP-PG12 in the two cell lines. Moreover, the rescuing effectiveness of PrP siRNAs was time-related, with the more efficient antagonism of the cytotoxicity of fCJD-associated PrP mutants occurring at the early stages after transfection. The data shown here provide useful clues for seeking potential therapeutic tools for prion diseases.

[siRNA-mediated inhibition of ErbB2 expression and its effect on breast cancer cell growth].

AIM: To construct a vector of ErbB2 small interfering RNA(siRNA), and to investigate its effect on ErbB2 expression and the growth of ZR75-1 breast cancer cells. METHODS: Two ErbB2-siRNAs were designed and inserted into the pSliencer 2.1-U6 neo vector. After confirmed by restriction and DNA sequencing, siRNA vectors were co-transfected with the FLAG-ErbB2 expression vector into human embryonic kidney 293T cells, or transfected into SKBR3 and ZR75-1 breast cancer cells. The effects of siRNAs on the expression of ErbB2 were identified by Western blot and the proliferation of ZR75-1 cells was repressed. RESULTS: Two siRNAs could effectively inhibit the expression of exogenous and endogenous ErbB2 proteins, and could repress the growth of ZR75-1 cells. CONCLUSION: ErbB2 siRNAs effectively inhibit the expression of ErbB2, thus repressing the growth of ZR75-1 cells.

A novel PrP partner HS-1 associated protein X-1 (HAX-1) protected the cultured cells against the challenge of H2O2.

Prion protein (PrP) is a ubiquitous conserved glycoprotein predominantly expressed in neurons of the central nervous system (CNS). To elucidate on its cellular function, we performed a yeast two-hybrid screen within an adult human brain cDNA library for potential PrP-binding molecules. A novel protein, HS-1 associated protein X-1 (HAX-1), was identified to be able to bind with PrP strongly. The interaction between the two proteins has been further verified by glutathione-S-transferase (GST) pull-down and immunoprecipitation assays. The minimal binding regions were mapped to the segments of residues aa 91-163 for PrP(C) and residues aa 38-129 for HAX-1. Immunofluorescent assays of co-expressions of human PrP and HAX-1 in 293T and SHSY-5Y cells revealed marked co-localizations of those two proteins in cytoplasm. Moreover, the co-expression of HAX-1 and wild-type PrP (PG5) was found to enhance the cellular resistance to the challenge of H2O2. Contrarily, co-transfection of HAX-1 did not reverse but aggravated the cytotoxicities of the genetic CJD (gCJD) associated PrP mutants with nine- (PG9) and fourteen-octarepeats (PG14). Our data provide for the first time a new PrP-interacting partner that may play role in cell oxidative stress and anti-apoptosis physiologically and cell damage pathologically.

Heat shock protein 104 inhibited the fibrillization of prion peptide 106-126 and disassembled prion peptide 106-126 fibrils in vitro.

Amyloid-like fibrils have been associated with the pathogenesis of human prion diseases. Prion peptide of aa 106-126 (PrP106-126) exhibits many PrP(Sc)-like biochemical features, forming amyloid-like fibrils in vitro. Here, we found that the recombinant yeast-derived molecular chaperon Hsp104 inhibited significantly the fibril assembly of the synthetic PrP106-126 peptide by dynamic ThT assays in vitro. EM assays revealed almost no fibril-like structure after incubation of the synthetic PrP106-126 peptides with Hsp104 for 12h. Circular dichroism assays identified that treatment of Hsp104 shifted the secondary structure of PrP106-126 fibrils from ß-sheet to a random coil. MTT tests confirmed that interaction of PrP106-126 with Hsp104 maintained the toxicity of PrP106-126 on human neuroblastoma cell line SK-N-SH. Additionally, Hsp104 was able to disassemble the mature PrP106-126 fibrils in vitro, leading to recovering the cytotoxicity of PrP106-126 on SK-N-SH cells. Our study provides the molecular evidences that the yeast-derived Hsp104 can interfere in the fibril assembly and disassembly of human PrP106-126 segment.

Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly.

Prion protein (PrP) is able to bind with tubulin and to interfere with the formation of microtubule. To investigate the influence of accumulation of cytosolic PrP in cytoplasm on microtubule, plasmid pcDNA3.1-PrP23-230 expressing human PrP23-230 was introduced into HeLa cells. Immunoprecipitation assays identified the molecular interaction between cytosolic PrP and cellular tubulin. Confocal microscopy showed the co-localization of the expressed cytosolic PrP with tubulin in cytoplasm. Immunofluorescent assays of tubulin illustrated remarkable disruption of microtubular structures in the cells accumulated with cytosolic PrP. Meanwhile, the expressed cytosolic PrP significantly reduced cell viability and induced cell apoptosis. The amounts of microtubule protein in the cells expressing cytosolic PrP were decreased. Moreover, the levels of endogenous tubulin in the brain tissues of scrapie-infected hamsters were significantly lower than that of normal one. It highlights a close linkage between disruption of microtubule framework and cell death caused by abnormal presence of cellular PrP in cytoplasm. The association of apoptosis with microtubule-disrupting activity caused by cytosolic PrP may further provide insight into the unresolved biological function of PrP in the neurons.

Establishment of hamster- and human-PRNP transgenic mice.

OBJECTIVE: To create transgenic mice expressing hamster- and human-PRNP as a model for understanding the physiological function and pathology of prion protein (PrP), as well as the mechanism of cross-species transmission of transmissible spongiform encephalopathies (TSEs). METHODS: Hamster and human-PRNP transgenic mice were established by conventional methods. The copy number of integrated PRNP in various mouse lines was mapped by real-time PCR. PRNP mRNA and protein levels were determined by semi-quantitative RT-PCR, real-time RT-PCR, and western blot analysis. Histological analyses of transgenic mice were performed by hematoxylin and eosin (H & E) staining and immunohistochemical (IHC) methods. RESULTS: Integrated PRNP copy number in various mouse lines was 53 (Tg-haPrP1), 18 (Tg-huPrP1), 3 (Tg-huPrP2), and 16 (Tg-huPrP5), respectively. Exogenous PrPs were expressed at both the transcriptional and translational level. Histological assays did not detect any abnormalities in brain or other organs. CONCLUSION: We have established one hamster-PRNP transgenic mouse line and three human-PRNP transgenic mouse lines. These four transgenic mouse lines provide ideal models for additional research.

[Inhibition of the expression of FHL2 by RNA interference].

AIM: To construct the eukaryotic expression vector of small interfering RNA (siRNA) targeting human FHL2 and transfect it into human embryo kidney 293T cells to investigate the silencing effect of FHL2 siRNA on the expression of FHL2 gene. METHODS: Two FHL2 siRNAs were designed and inserted into pSliencer 2.1-U6 neo expression vector. Then human embryo kidney 293T cells were cotransfected with the recombinant plasmids and FLAG-tagged FHL2 expression vector. The silencing effect of FHL2 siRNAs on the expression of FHL2 gene was identified by Western blot. RESULTS: The expression vectors of FHL2 siRNAs were constructed and confirmed by DNA sequencing. Western blot showed that FHL2 siRNAs effectively inhibited expression of FHL2. CONCLUSION: The eukaryotic expression vectors of FHL2 siRNAs are constructed successfully. The siRNAs effectively inhibit the expression of FHL2.

[Establishment of estrogen receptor alpha trans-activation system].

OBJECTIVE: To construct estrogen receptor alpha (ERalpha) trans-activation system. METHODS: The full length ERalpha and its different function regions [(transcriptional activation function 1 (AF1), DNA binding domain (DBD), and transcriptional activation function 2 (AF2)] were amplified from pcDNA3-ERalpha by PCR and cloned into the pGAL vector. The expressions of the recombinant plasmids constructed were detected via immunoblotting. The 293T cells transfected with recombinant plasmids of full length ERalpha, its different function regions and empty vector were divided into 5 groups; each group was divided into 2 parts which were treated with or without estrogen (E(2)). The transcriptional activity of each group was detected in 293T cells after the recombinant plasmid was co-transfected with 0.2 microg of estrogen receptor element luciferase (ERE-LUC) and 0.1 microg of plasmid expressing beta-galactosidase and treated with or without 10 nmol/L E(2) for 24 hours. RESULTS: The full length ERalpha and its different function regions were expressed in the 293T cells. Compared with the empty pGAL vector, the transcription activities of full length ERalpha, AF1, AF2 and DBD recombinant plasmids were raised about 20.44 +/- 1.01, 2.09 +/- 0.11, 8.09 +/- 0.30 and 1.05 +/- 0.09 fold, respectively, with the induction of E(2) after transfection in the 293T cells. CONCLUSION: The trans-activation system of ERalpha has been successfully established.