[Analysis of the correlative factors of long-term positive nucleic acid and the characteristics of nucleic acid conversion in novel coronavirus infected patients].

To analyze the correlative factors of long-term positive nucleic acid and the characteristics of negative nucleic acid conversion in novel coronavirus infected patients.Novel coronavirus infected patients who were hospitalized in Beijing Tsinghua Changgung Hospital from December 2022 to June 2023 were retrospectively included. Patients who were positive for novel coronavirus nucleic acid for ≥30 days were selected as the long-positive group, and age-and sex-matched patients with novel coronavirus nucleic acid for <30 days were selected as the control group. The clinical data of all enrolled patients were collected. Binary logistic regression was used to analyze the influencing factors of the positive duration of nucleic acid ≥30 days. The Cox risk ratio model was used to analyze the risk factors for the prognosis of severe patients during hospitalization, and the difference in the time of nucleic acid conversion between the upper and lower respiratory tract was compared between the groups. A total of 30 patients were included in the long-positive group, including 24 males and 6 females, aged [M (Q1, Q3)] 77 (64, 86) years. Fifty-eight patients were included in the control group, including 46 males and 12 females, aged 78 (66, 86) years. Transplantation status (OR=50.32, 95%CI: 1.98-1 278.63, P=0.018), malignant tumor (OR=12.85, 95%CI: 1.65-99.88, P=0.015), CD4+T cell count (OR=0.99, 95%CI: 0.99-1.00, P=0.005) were correlative factors for positive nucleic acid≥30 days. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score (HR=1.12, 95%CI: 1.03-1.22, P=0.012) and nucleic acid positive time (HR=1.16, 95%CI: 1.01-1.33, P=0.031) were correlative factors for death in severe patients. The nucleic acid conversion time of the lower respiratory tract specimens in both groups was later than that of the upper respiratory tract specimens (all P<0.001). Weakened underlying immunity is a correlative factor for long-term novel coronavirus nucleic acid positivity, and long-term positive novel coronavirus nucleic acid in severe patients indicates high risk of death. The nucleic acid of the lower respiratory tract specimen turned negative later than the upper respiratory tract specimen.

[Analysis of factors of elder patients with lumbar vertebrae fractures caused by low-energy injury in plateau area].

Objective: To analyse the factors of elder patients with lumbar vertebrae fractures caused by low-energy injury in plateau area. Methods: From March 2013 to September 2016, 124 elder patients with lumbar vertebrae fractures caused by low-energy injury in our hospital were selected as observation group, in the corresponding period, 98 elderly patients who had no fractures were considered as control group .The bone mineral density (BMD) was examined by whole body bone mineral density tester, and univariate analysis and multivariate Logistic regression analysis were used to analyze the influencing factors of lumbar fractures caused by low-energy injury. Results: BMD and T value of lateral projection of lumbar vertebrae in observation group were significantly lower than those in control group (P<0.05). Single factor analysis showed that the age, body mass index, past history, bone mineral density and calcium supplementation had a significant effect on lumbar fractures caused by low-energy injury. Logistic regression analysis showed that age (OR=1.215), bone mineral density (OR=3.215) and calcium supplementation (OR=4.904) were independent risk factors for lumbar fractures caused by low-energy injury (P<0.05). Conclusion: Bone mineral density of elderly population in plateau area is lower. Age, bone mineral density and calcium supplementation are independent risk factors of lumbar fractures caused by low-energy injury, and individual medical intervention is needed.

Assembly of body-centered cubic crystals in hard spheres.

We investigate the crystallization of monodisperse hard spheres confined by two square patterned substrates (possessing the basic character of the body-centered cubic (bcc) crystal structure) at varying substrate separations via molecular dynamics simulation. Through slowly increasing the density of the system, we find that crystallization under the influence of square patterned substrates can set in at lower densities compared with the homogeneous crystallization. As the substrate separation decreases, the density, where crystallization occurs (i.e., pressure drops), becomes small. Moreover, two distinct regimes are identified in the plane of bcc particle fraction and density for the separation range investigated. For large substrate separations, the bcc particle fraction displays a local maximum as the density is increased, and the resulting formed crystals have a polycrystalline structure. However, and more importantly, another situation emerges for small substrate separations: the capillary effects (stemming from the presence of two substrates) overwhelm the bulk driving forces (stemming from the spontaneous thermal fluctuations in the bulk) during the densification, eventually resulting in the formation of a defect-free bcc crystal (unstable with respect to the bulk hard-sphere crystals) by using two square patterned substrates.

HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation.

Eighteen histone deacetylases (HDACs) are present in humans, categorized into two groups: zinc-dependent enzymes (HDAC1-11) and NAD(+)-dependent enzymes (sirtuins 1-7). Among zinc-dependent HDACs, HDAC6 is unique. It has a cytoplasmic localization, two catalytic sites, a ubiquitin-binding site, and it selectively deacetylases alpha-tubulin and Hsp90. Here, we report the discovery that the redox regulatory proteins, peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6. Prx are antioxidants enzymes whose main function is H(2)O(2) reduction. Prx are elevated in many cancers and neurodegenerative diseases. The acetylated form of Prx accumulates in the absence of an active HDAC6. Acetylation of Prx increases its reducing activity, its resistance to superoxidation, and its resistance to transition to high-molecular-mass complexes. Thus, HDAC6 and Prx are targets for modulating intracellular redox status in therapeutic strategies for disorders as disparate as cancers and neurodegenerative diseases.

Dense packing in the monodisperse hard-sphere system: a numerical study.

We report a numerical study of the close packing of monodisperse hard spheres. The close packings of hard spheres are produced by the Lubachesky-Stillinger (LS) compression algorithm and span the range from the disordered states to the ordered states. We provide quantitative evidence for the claim that the density and structural order of the arrested close packing can be determined by the compression rate, i.e., with slower rates producing denser and more ordered structures. Through deeply analyzing the structure of the resulting arrested close packings, a transition region has been identified in the plane of density and reciprocal compression rate, in between what have been historically thought of as amorphous and crystalline packings. We also find clear system size dependences in studying the structural properties of the packings from the disordered ones to the ordered ones. These detailed investigations, on the structure of the arrested close packings, may provide a link between the glassy states and the crystalline states in the hard spheres.

Histone deacetylase inhibitors: Potential in cancer therapy.

The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation. There are 18 HDACs in humans. These enzymes are not redundant in function. Eleven of the HDACs are zinc dependent, classified on the basis of homology to yeast HDACs: Class I includes HDACs 1, 2, 3, and 8; Class IIA includes HDACs 4, 5, 7, and 9; Class IIB, HDACs 6 and 10; and Class IV, HDAC 11. Class III HDACs, sirtuins 1-7, have an absolute requirement for NAD(+), are not zinc dependent and generally not inhibited by compounds that inhibit zinc dependent deacetylases. In addition to histones, HDACs have many nonhistone protein substrates which have a role in regulation of gene expression, cell proliferation, cell migration, cell death, and angiogenesis. HDAC inhibitors (HDACi) have been discovered of different chemical structure. HDACi cause accumulation of acetylated forms of proteins which can alter their structure and function. HDACi can induce different phenotypes in various transformed cells, including growth arrest, apoptosis, reactive oxygen species facilitated cell death and mitotic cell death. Normal cells are relatively resistant to HDACi induced cell death. Several HDACi are in various stages of development, including clinical trials as monotherapy and in combination with other anti-cancer drugs and radiation. The first HDACi approved by the FDA for cancer therapy is suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza), approved for treatment of cutaneous T-cell lymphoma.

Histone deacetylase inhibitors: molecular mechanisms of action.

This review focuses on the mechanisms of action of histone deacetylase (HDAC) inhibitors (HDACi), a group of recently discovered 'targeted' anticancer agents. There are 18 HDACs, which are generally divided into four classes, based on sequence homology to yeast counterparts. Classical HDACi such as the hydroxamic acid-based vorinostat (also known as SAHA and Zolinza) inhibits classes I, II and IV, but not the NAD+-dependent class III enzymes. In clinical trials, vorinostat has activity against hematologic and solid cancers at doses well tolerated by patients. In addition to histones, HDACs have many other protein substrates involved in regulation of gene expression, cell proliferation and cell death. Inhibition of HDACs causes accumulation of acetylated forms of these proteins, altering their function. Thus, HDACs are more properly called 'lysine deacetylases.' HDACi induces different phenotypes in various transformed cells, including growth arrest, activation of the extrinsic and/or intrinsic apoptotic pathways, autophagic cell death, reactive oxygen species (ROS)-induced cell death, mitotic cell death and senescence. In comparison, normal cells are relatively more resistant to HDACi-induced cell death. The plurality of mechanisms of HDACi-induced cell death reflects both the multiple substrates of HDACs and the heterogeneous patterns of molecular alterations present in different cancer cells.

A Prediction Model of the Capillary Pressure J-Function.

The capillary pressure J-function is a dimensionless measure of the capillary pressure of a fluid in a porous medium. The function was derived based on a capillary bundle model. However, the dependence of the J-function on the saturation Sw is not well understood. A prediction model for it is presented based on capillary pressure model, and the J-function prediction model is a power function instead of an exponential or polynomial function. Relative permeability is calculated with the J-function prediction model, resulting in an easier calculation and results that are more representative.

Bevacizumab in combination with first-line chemotherapy in patients with metastatic colorectal cancer: a meta-analysis.

Bevacizumab plays an important role in the treatment of patients with metastatic colorectal cancer (mCRC). The aim of this study is to assemble current RCTs to analyze efficacy of adding bevacizumab to the most used combination first-line chemotherapy in mCRC patients. PubMed, Web of Science, the Cochrane Library and Embase were systematically searched. Our primary endpoint was overall survival (OS), progression-free survival (PFS) and secondary endpoint was overall response rate (ORR). Hazard ratios (HRs) for PFS and OS and risk ratio (RR) for ORR were extracted from each trial. All these above were performed using a random-effects model and statistics was performed in StataSE 12.0. Seven randomized controlled studies aggregating 3264 patients were enrolled in our meta-analysis. OS, PFS and ORR were performed using a random-effects model. A therapeutic effect advantage was showed in Bevacizumab added to first-line chemotherapy with higher OS (HR=0.67; 95% CI=0.61-0.72; P=0.000), PFS (HR=0.67; 95% CI=0.61-0.72; P=0.000) compared with chemotherapy alone. Chemotherapy plus bevacizumab increased ORR (38.42% vs. 33.44%), showing statistically difference (RR=1.17, 95% CI=1.06-1.28, P=0.001). Our meta-analysis shows that the addition of bevacizumab to first-line regimens can be beneficial in terms of OS, PFS and ORR compared with chemotherapy alone.

Detection of trisomy 3 in primary gastric B-cell lymphoma by using chromosome in situ hybridization on paraffin sections.

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.

High incidence of BCL-6 gene rearrangement in diffuse large B-cell lymphoma of primary gastric origin.

The incidence of BCL-6 gene rearrangement was studied in 39 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary site of involvement was nodal in 18 cases and gastric in 21 cases. Clonal BCL-6 gene rearrangement was found in 17% of the patients with primary nodal and 48% with primary gastric lymphoma (p = 0.05). The clinical characteristics and treatment outcome of the 21 patients with primary gastric lymphoma were analyzed according to the BCL-6 status. Significantly more patients in the germline BCL-6 gene group had advanced stage (II, III and IV) of disease. Complete remission rate following primary therapy appeared to be higher for the positive rearrangement group (70% versus 36%), but it was not statistically significant. Those with a rearranged BCL-6 gene also appeared to have better survival at 5 years (58% versus 36%) but the difference was also not statistically significant. On the other hand, patients being classified as low risk according to the International Prognostic Index had significantly better survival at 5 years (89% versus 9%, p = 0.0001). We concluded that BCL-6 gene rearrangement was more commonly found in diffuse large B-cell lymphoma of primary gastric origin than its nodal counterpart and it may be playing a more important role in the pathogenesis of gastric large B-cell lymphoma. There was a trend that the BCL-6 gene rearrangement was associated with a more favorable outcome in patients with gastric large B-cell lymphoma but the difference was not statistically significant.

Mutation of the 5' noncoding region of the BCL-6 gene in low-grade gastric lymphoma of the mucosa-associated lymphoid tissue.

BCL-6 gene rearrangement and hypermutations were investigated in four Hong Kong Chinese patients with low-grade gastric lymphoma of the mucosa-associated lymphoid tissue (MALToma). The former was studied by Southern analysis and the latter by the technique of polymerase chain reaction and denaturing gradient gel electrophoresis. BCL-6 gene rearrangement was not detectable in any of the four cases. However, mutations at both the E1.11 and E1.12 segments of the 5' noncoding region of the BCL-6 gene were found in two patients. This preliminary observation suggests that the mutations of the 5' noncoding region of the BCL-6 gene rather than gene rearrangement may be playing a more important role in the tumorigenesis of low-grade gastric MALToma. Further confirmation of this finding by studying a larger number of patients will be required.

Immunization with interleukin-2/interferon-gamma double cytokine-secreting allogeneic fibroblasts prolongs the survival of mice with melanoma.

LM mouse fibroblasts (H-2k) were modified for the expression of (antibody-defined) melanoma-associated antigens (MAA) and the secretion of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) (RLBA-IL-2/IFN-gamma cells). The cell construct was tested for its immunogenic properties in C57BL/6 mice (H-2b) with B16 melanoma. The results indicated that the survival of mice injected with a mixture of B16 cells and the modified, double cytokine-secreting fibroblasts was significantly longer than that of mice injected with B16 cells and LM cells modified for the expression of MAA and the secretion of IL-2 or IFN-gamma alone (RLBA-IL-2 or RLBA-IFN-gamma cells). Both natural killer/lymphokine-activated killer (NK/LAK) cells and Lyt-2.2 + CTLs with anti-melanoma cytotoxic activities were predominant in mice immunized with the double cytokine-secreting cells. B16 melanoma cells persisted in mice treated with RLBA-IL-2 cells (B16-R3). The B16-R3 cells were resistant to anti-melanoma effector cells from mice immunized with RLBA-IL-2 cells. The recurrent melanoma cells were deficient in the expression of MHC class I determinants. Class I expression by B16-R3 cells was increased if they were incubated in medium conditioned by the growth of IFN-gamma-secreting RLBA-IL-2/IFN-gamma or RLBA-IFN-gamma cells. After incubation, the sensitivity of B16-R3 melanoma cells to immune-effector cells from mice immunized with RLBA-IL-2 cells was restored. The survival of mice bearing low MHC class I-expressing B16-R3 cells, treated RLBA-IL-2/IFN-gamma cells, was determined. The treated animals survived significantly longer than mice with B16-R3 melanoma treated with RLBA-IL-2 cells. Similar results were obtained for mice with B16-R3 melanoma treated with RLBA-IFN-gamma cells. We postulate that immunization of mice with IL-2/IFN-gamma double cytokine-secreting cells stimulated multiple anti-melanoma effector mechanisms. Analogous to the enhanced therapeutic anti-tumour effects of combination chemotherapy, it was likely that treatment with a cellular immunogen engineered to stimulate more than one effector mechanism resulted in the elimination of larger numbers of tumour cells than treatment with an immunogen that stimulated a single effector mechanism alone.

Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.

This study examines the basis of resistance and sensitivity of normal and transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically the role of caspases and thioredoxin (Trx). An important attribute of HDACis is that they induce cancer cell death at concentrations to which normal cells are relatively resistant, making them well suited for cancer therapy. The mechanism underlying this selectivity has not been understood. In this study we found that the HDACi suberoylanilide hydroxamic acid (SAHA) and MS-275, a benzamide, cause an accumulation of reactive oxygen species (ROS) and caspase activation in transformed but not normal cells. Inhibition of caspases does not block HDACi-induced cell death. These studies provide a possible mechanism that can explain why normal but not certain transformed cells are resistant to HDACi-induced cell death. The HDACi causes an increase in the level of Trx, a major reducing protein for many targets, in normal cells but not in transformed cells. The SAHA-induced increase in Trx activity in normal cells is associated with no increase in ROS accumulation. Transfection of transformed cells with Trx small interfering RNA caused a marked decrease in the level of Trx protein with an increase in ROS, a decrease in cell proliferation, and an increase in sensitivity to SAHA-induced cell death. Thus, Trx, independent of the caspase apoptotic pathway, is an important determinant of resistance of cells to HDACi-induced cell death.

[Analysis of the cultural and mental diseases rates of the three nationalities from She, Hui and Mongolian peoples].

This paper researches into transcultural psychiatry from She. Hui and Mongolian Nationalities in an epidemiological fact-finding way. Its results show that different historical cultural background geographical environment and custom of these three nationalities closely related to mental health including the sickness rates the symptoms and the kinds of mental disease.

[Effect of the use of human hyperimmune plasma against Pseudomonas protein for protection against Pseudomonas sepsis in burn mice].

A controlled study was performed to evaluate the efficacy of human hyperimmune plasma (HIP) for protecting burned mice from Pseudomonas infection. The HIP was prepared from healthy volunteers immunized with endotoxin protein (Ep) of Pseudomonas aeruginosa. It contained antibody against Ep up to the titre higher than 1:128. Mice with full-thickness burn of 13% TBSA, infected by subeschar injection of 0.2 ml P. aeruginosa (CFU/ml), were treated with HIP at 6 hrs and 18 hrs postburn. The survival rate of the former on the 7th day was 45%, while in mice treated with normal plasma (NP) was 14% and in control mice 10% (P < 0.01). If the HIP was given 18h after burn, the survival rate was 43%, while in mice with NP was 39% and in control 42% (P > 0.05). The results indicate that HIP is able to protect burned mice from Pseudomonas infection giving at 6 hrs postburn (pre sepsis) but not at 18 hrs postburn (post sepsis).