Search

壶腹部发生的浸润性微乳头状癌罕见，本文报道1例发生于80岁老年女性的病例，肿瘤表面呈壶腹内乳头状管状肿瘤，下方浸润成分以微乳头状癌为主。肿瘤同时显示肠型、胰胆管/胃型的特征，为混合型。微乳头状癌区可见特征性的中性粒细胞浸润。目前需要积累该部位的病例以形成WHO壶腹部肿瘤分类的独立组织学亚型。.

Oxaliplatin-induced neuropathy is a significant complication of cancer therapy. We aimed at investigating the risk factors of oxaliplatin-induced neuropathy (OIPN) and providing evidence to enhance its prevention.PubMed, Medline, Web of Science, Embase, China Knowledge Resource Integrated Database, and the Wanfang Database were searched comprehensively for observational studies investigating the prevalence and risk factors of OIPN from inception to November 30, 2021. The Newcastle-Ottawa Scale was used by two independent reviewers to assess methodological quality. When applicable, we used meta-analysis to determine mean differences and odds ratios for continuous and nominal scaled data.We included 20 studies involving 10,900 participants for analysis. Factors associated with OIPN risk identified by meta-analysis were age, gender, diabetes, anemia, hypomagnesaemia, alcohol consumption, body mass index, body surface area, cumulative oxaliplatin dose and the number of chemotherapy cycles. Factors not associated with OIPN risk included smoking history and chemotherapy regimen.This meta-analysis identified multiple variables associated with OIPN. The recognition of modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.

Random Telegraph Noise (RTN)/fluctuation is one of the most serious reliability issues in modern deeply scaled CMOS. The current RTN characterization methods need to select devices and can only capture the fast traps, thus it is very difficult to predict and validate device long-term fluctuation behavior. A new fast and test-proven methodology of assessing RTN/fluctuation is proposed in this work. By using the Within Device Fluctuation (WDF), all the devices’ fluctuation can be captured. Moreover, WDF can be well explained and simulated as a sum of all the As-grown Traps (AT) induced RTN.

In the design of large-scale steel structure, the design calculation of the structure is usually based on the service state. But in the process of steel structure construction, the displacement and stress produced in the construction process cannot be completely consistent with that in the design state. With the progress of construction process, the deformation and stress caused by self-weight and construction load gradually accumulate until the structure is formed, which will produce construction error relative to the design state. In this paper, FEM method was used to simulate the construction process of the steel grid roof of the theater in the Beijing Sub Center Theater project, and the influence of the accumulated deformation and stress on the mechanical properties of the structure during the construction process was analyzed. The results show that the cumulative deformation and stress in the construction process have a great influence on the final deformation and stress distribution of the structure. The maximum vertical displacement in the actual construction state is 599.6% of that in the design state, and the maximum stress is 119.7% of that in the design state. This will lead to the difference between the construction-completed structure and the design structure, which makes the design result dangerous. The measures to optimize the construction process were also given in this paper, which provides guidance for the construction process of large-scale steel structure.

目的 探索稳定过表达CD99前后霍奇金淋巴瘤细胞株L428细胞中差异表达的蛋白，并分析验证差异蛋白的功能。 方法 采用荧光差异凝胶双向电泳和质谱分析技术检测L428细胞稳定过表达CD99前后蛋白表达的差异，采用GOfact开放软件对差异蛋白进行聚类分析，筛选在细胞转化过程中起重要作用的蛋白，并分析验证其功能。 结果 筛选鉴定得到38个差异蛋白，其中在稳定过表达CD99的霍奇金淋巴瘤细胞株L428（L428-CD99细胞）中与CD99表达呈正相关的蛋白21个，呈负相关的蛋白17个，所得的38个差异蛋白中有32个蛋白参与了细胞的生物过程，35个蛋白参与了细胞的组成和构建，28个参与了抗氧化、蛋白结合、催化活性、酶调节、信号转导、结构分子、翻译调节和离子转运等多个方面。 结论 筛选得到38个差异蛋白，其中关于细胞骨架、细胞分化、信号通路、调节基因表达等蛋白的改变与H/RS细胞和B淋巴瘤细胞转化相关。

The aim of this study was to investigate the effects of miR-92b-5p inhibitor and interleukin-18-binding protein (IL-18BP) on interleukin-18 (IL-18)-mediated inflammatory response after spinal cord injury (SCI).In this work, microglia was isolated from the newborn C57/B6J mice spinal cord to in vitro culture. The expression of IL-18BP and IL-18 was measured by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) after transfection of miR-92b-5p into activated microglia. The expression of IL-18BP and IL-18 was determined following miR-92b-5p inhibitor treatment. In addition, the spinal cord injury model was established in mice. The expressions of miR-92b-5p, IL-18BP, and IL-18 were measured by qRT-PCR, and the expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1 β) were determined by Western blot. After intrathecal injection of miR-92b-5p inhibitor, the mRNA expression of miR-92b-5p, IL-18BP, and IL-18 and the expression of iNOS, TNF-α, and IL-1 β in the injured area of the spinal cord of mice were measured. Basso Mouse Scale (BMS) was used to determine the recovery of locomotor function after spinal cord injury and miR-92b-5p inhibition.After miR-92b-5p transfection, the expression of IL-18BP was significantly decreased compared with that of untransfected microglia cells, whereas the level of IL-18 mRNA was significantly increased. However, the level of IL-18BP elevated significantly and the level of IL-18 reduced markedly after treatment with corresponding inhibitors. In addition, compared with the sham operation group (Sham), the RNA level of miR-92b-5p in the SCI group was significantly higher than that in the Sham, but the expression of IL-18BP was evidently declined and the expression of IL-18 was significantly increased in the SCI group. Meanwhile, the expression of miR-92b-5p in miR-92b-5p inhibitor intrathecal injection mice was remarkably lower than that in SCI group, the expression level of IL-18BP was significantly increased, and the RNA expression of IL-18 was weakened accordingly. Moreover, the protein expression of iNOS, TNF-α, and IL-1 β in miR-92b-5p inhibitor-treated mice was significantly lower than that in the SCI group. The locomotor evaluation of miR-92b-5p inhibitor group was dramatically higher than that of the SCI group.Suppressing the expression of miR-92b-5p after SCI can effectively intensify the level of IL-18BP, reduce the expanded inflammatory effect of IL-18, decline the release of iNOS, TNF-α, and IL-1 β, thus alleviate the neuronal injury and improve the locomotor function after SCI.

To conduct analysis and prenatal diagnosis on 11 couples carrying Thailand deletion (--(THΑI)) α-thalassemia 1, so as to provide information for clinical genetic counseling on α-thalassemia 1.Altogether 11 Thailand deletion (--(THΑI)) α-thalassemia 1 families were collected from Fujian Maternal and Children Health Hospital from May 2009 to September 2015. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the thalassemia mutations in the couples and fetuses.In one family, Thailand deletion α-thalassemia 1 was detected in both the pregnant woman and her husband. In 10 families, Thailand deletion α-thalassemia 1 was detected in either the pregnant women or the husband, while the spouses had α-thalassemia heterozygote (1 combined with β thalassemia heterozygote). Thailand deletion α-thalassemia 1 family members all had lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). In prenatal diagnosis of the 12 fetuses, 4 fetuses were found with hemoglobin(Hb) Bart's hydrops fetalis syndrome, 5 were with α-thalassemia heterozygote, and 3 were normal.For couples with positive hematological phenotype but normal results in routine genetic examination of α-thalassemia, attention should be paid especially for with a history of having babies of hydrops fetalis syndrome or hemoglobin H disease. It is necessary to consider the possibility of the rare Thailand deletion (--(THΑI)) α-thalassemia 1. Prenatal diagnosis for high-risk families plays an important role.

Acute Fibrinous and Organizing Pneumonia (AFOP) is a new pathologic pattern of acute lung injury characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" in a patchy distribution.A 65-years-old female after a surgical resection of rectal adenocarcinoma presented with typical manifestations of hospital-acquired pneumonia, but she didn't respond to the anti infective therapy. After an explicit diagnosis of AFOP via percutaneous needle lung biopsy, she got an impressive improvement with a long-term therapy of methylprednisolone and low-dose indomethacin. To date, a total of non-overlapped 45 individual AFOP cases and 4 single-center studies involving AFOP have been reported. The most common coexisting diseases are infections, connective tissue diseases and hematological diseases. Corticosteroids and immunosuppressants are the most common agents prescribed in AFOP. The prognosis of AFOP is unfavorable, associated with the pathologic characteristics and the clinical parameters.The immune system activated by infection may play an important role in the pathogenesis of AFOP. Low-dose indomethacin combined with methylprednisolone may be a new choice for AFOP treatment.

To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis.The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy. The result was analyzed in combination with clinicopathological data.The proportion of regulatory T cells (Treg) after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034). The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survival (OS). The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg, which was 23.5 and 9.4 months respectively (P0.05).The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

In this experiment in in vitro conserved embryogenic calli of 15 cultivars in longan were used as the materials for the studies on the induction, maturation and regeneration of somatic embryos. The results showed that the somatic embryogenesis was different among these 15 cultivars. During the induction of somatic embryo-genesis, sucrose concentrations, organic substances supplied, plant growth regulators and light quality affected the time, quantity and quality of somatic embryogenesis in different degrees. Somatic embryogenesis occurred from 15 to 35 d after induction, many of the embryoids were white in color, the frequency of somatic embryogenesis was all 100%, and the number of differentiated embryoids was from 2550-13220 per gram callus. In the stage of embryoid maturation, concentrations of sucrose, organic substances and light quality affected the size and the shape of matured embryoids, from 5 to 15 mm in size. The results showed that the maturation time, different types of somatic embryogenesis and light quality had great effects on the germination rates and growth of somatic embryos. Most of the normal matured somatic embryos germinated after transferred to germination medium for 15 d, and the germination rates were different from 55 to 93.3% among 15 cultivars.

Somatic embryogenesis system in longan can serve as a model experimental system of woody plants. Since 2000, on the basis of histological and cytological observations, determination of endogenous hormones and polyamines (PAs), the changes of isozymes and proteins by PAGE, IEF and SDS- PAGE analysis during longan somatic embryogenesis proteomics and molecular biology during longan somatic embryogenesis have been carried out by mRNA differential display, homologous cloning, fluorescence quantitative PCR, 2-DE and bio-mass spectrometry (MALDI-TOF or Q-TOF2) technique, to uncover the molecular mechanism of longan somatic embryo- genesis, and provide scientific evidence for regulating longan embryo development.

A 44-year-old man presented with chronic, persistent cough and occasional wheezing. Airflow obstruction, blood eosinophilia and a remarkable elevated level of serum carcinoembryonic antigen (CEA) were found. Radiographic and pathological studies confirmed eosinophilic bronchiolitis. There was no evidence of neoplasms by extensive examinations. After a protracted oral steroid therapy, the blood eosinophil count, the serum CEA level and the lung lesions were all improved in parallel, whereas fixed airflow obstruction remained. This case was diagnosed as a new distinct syndrome, hypereosinophilic obliterative bronchiolits. Serum CEA and blood eosinophil cell count served as good markers of the disease condition for this syndrome.

There exist reports that statin treatment has beneficial effects for patients with pneumonia. The objective of this study was to evaluate whether the available published data support that statins as adjunctive therapy could reduce mortality associated with pneumonia and, thus, help to assess whether a randomized controlled study is warranted.A meta-analysis of observational studies such as cohort studies and case-control studies identified in Pubmed, Scopus, EMBASE, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov. Eligible patients were adults with pneumonia. Studies that reported mortality of pneumonia grouped by statins usage were included. Data was analyzed and pooled using Revman 5.1.Fourteen studies with 269,739 participants were included in this study. Pooled analysis showed that statin treatment was associated with lower 30-day mortality, with an OR of 0.44 (95% CI, 0.29-0.67), and an adjusted OR of 0.59 (95% CI 0.48-0.73, NNT30d = 19). Statin therapy was also associated with lower long-term (30 days) mortality, with an OR of 0.49 (95% CI, 0.29-0.84) and an adjusted OR of 0.65 (95% CI, 0.51-0.82, NNTlong-term = 15). For pneumonia inpatients, the raw data demonstrated no significant benefit from statin therapy (OR = 0.86, 95% CI, 0.56-1.34). Adjusted data showed a marginal benefit (adjusted OR = 0.89, 95% CI, 0.81-0.97, NNTinpatient = 230). Subgroup analysis revealed that current statin users might have better outcomes than recent or past statins users.This meta-analysis supports that patients who happen to be receiving statin therapy have less mortality from pneumonia. However, it remains unclear whether initiation of statins at time of diagnosis is beneficial. There is only modest evidence to support the value of a well-designed randomized controlled clinical trial.

TRAIL (TNF-related apoptosis inducing ligand) belongs to the tumor necrosis factor (TNF) cytokine family, can induce apoptosis in a wide variety of tumor cell lines. This review introduces research progress on TRAIL from several aspects: the structure and function of TRAIL, the pathway of its inducing apoptosis, TRAIL and cancer treatment, and its foreground.

A rapid enantiomeric separation method using L-leucine as chiral selector was established. Capillary zone electrophoresis (CZE) has been used for the enantiomeric separation of twelve pharmaceutical racemates with bare fused silica capillary and employing L-leucine as chiral selector. The enantiomeric resolution was influenced by L-leucine concentration and pH of background electrolyte (BGE). The effects of the BGE types and concentrations on the enantiomeric separation were also investigated. The results showed that in the solution containing 50 mmol/L borax and 70 mmol/L L-leucine (pH 9.0), all the twelve drugs were on baseline separated in less than 11 minutes.

In order to study the relationships of aspartic proteases, we have modified pepsin, a single-chain eukaryotic enzyme, to a two-chain heterodimer, which resembles aspartic proteases from retrovirus, including human immunodeficiency virus. Two fragments of pepsinogen, residues 1P-172 and 173-326, were expressed separately in Escherichia coli. Mixtures of chains were refolded from urea solutions to generate an active two-chain pepsinogen, which was converted to two-chain pepsin in acid solutions. The intramolecular and bimolecular activation constants (k1 and k2) of two-chain pepsinogen are about 1.5-fold and one-sixth, respectively, of those for pepsinogen. Structural evidence suggests that the faster k1 of two-chain pepsinogen is due to decreased interaction of the propeptide with the pepsin moiety, implying that the rate-limiting step in the intramolecular activation of pepsinogen is the "conformational dissociation" of its propeptide. Two-chain pepsin has the same Km but only one-sixth of the kcat of pepsin. Both pepsinogen chains are capable of independent refolding. The refolding of the NH2-terminal chain, which contains the propeptide and the NH2-terminal lobe, generated a small amount of proteolytic activity which is likely derived from the homodimer of the NH2-terminal lobe. It has been postulated that mammalian aspartic proteases, which contain two structurally homologous lobes, are derived in evolution from a homodimer enzyme by gene duplication and fusion (Tang, J., James, M. N. G., Hsu, I.-N., Jenkins, J. A., and Blundell, T. L. (1978) Nature 271, 618-621). The observation of the homodimer activity of the NH2-terminal lobe of pepsinogen suggests that the interface of the lobes is conservative in evolution.

A cDNA clone, which contained the complete rhizopuspepsin structure and the putative proregion, was placed in three different Escherichia coli expression vectors for the synthesis of rhizopuspepsinogen (Rpg). Recombinant Rpgs which were expressed in the cytosol of E. coli as inclusion bodies (cRpg and tRpg) were not active. After solubilization in 6 M urea and refolding by rapid dilution, both of these Rpgs were purified to homogeneity. The third zymogen, pRpg, which was secreted to the periplasmic space of E. coli with an omp leader, was fully active and also was purified. The expression level of pRpg was higher (over 40 mg/liter culture) than that of cRpg (about 1.5 mg/liter culture). Amino-terminal sequence analysis of the zymogens revealed that cRpg and pRpg contain 40 and 51 residues of prosequence, respectively. tRpg, which was expressed under the control of T7 promoter, was synthesized at 500 mg/liter culture and was purified at 50 mg/liter culture. This zymogen contained, in addition to 51 residues of proregion, 16 residues inherited from the expression vector construction. All of these Rpgs spontaneously converted to rhizopuspepsin in solutions of pH less than 5. Each of the conversions was associated with a change of molecular weight as monitored in sodium dodecyl sulfate-polyacrylamide electrophoresis. At least one intermediate of conversion was observed in the pH range of 2 to 3 for both the cRpg and pRpg zymogens. For pRpg and tRpg, kinetic data demonstrated that the Rpg to rhizopuspepsin conversion was accomplished by a first order, unimolecular reaction at pH 2. The first order kinetic constants in this pH at 15 degrees C were 1.1 and 2.4 min-1 for pRpg and tRpg, respectively. The activation rate decreased as pH was raised above pH 2. At pH greater than 3.0, rhizopuspepsin-catalyzed, second-order activation also takes place. Consequently, the recombinant Rpgs are activated by either of two cleavage mechanisms as is the case for pepsinogen. These results also support the hypothesis that Rpg is synthesized in Rhizopus chinensis as a zymogen. Rpg in the host fungus is probably activated by an acid environment of pH less than 5 in the secretory granules to become rhizopuspepsin before secretion.

This paper reports on an in vitro culture system for the exoerythrocytic (EE) stage of Plasmodium berghei (P.b.) using embryonic lung cells. The system was first developed by our laboratory in China. The embryonic lung cells were isolated by trypsin digestion of a human embryonic lung obtained from a therapeutic abortion case and was designated as cell line Elu 8801. Anopheles stephensi mosquitoes were infected by biting P.b. ANKA strain infected Kunming mice and after 18-21 days were dissected under aseptic conditions for preparation of a sporozoite suspension. This suspension was used to inoculate the monolayer cultures of Elu 8801. Regular examination found that following a cultivation for 48 hours, up to 100 multinuclear EE schizonts of P.b. could be observed on 1 x 1 cm cover slide. Seventy-two hours later mature merozoites were seen among part of the schizonts. An intraperitoneal inoculation of the supernatant culture medium to mice could induce malaria infection which could be transferred to other mice by blood inoculation. When the mice infected with the second generation were allowed to feed A. stephensi, sporozoites developed in the mosquitoes. The results demonstrate that the human embryonic lung cell line Elu 8801 established in our laboratory is susceptible to P.b. ANKA sporozoites and can support the developmental maturation of EE stages, producing potentially infectious merozoites.

AIM: To clone the cDNA fragment of human TRAIL (TNF-related apoptosis inducing ligand) into a tetracycline-regulated gene expression system, the RevTet-On system, transduce expression vectors into a gastric carcinoma cell line-NCI-N87 and examine the effects of controlled expression of TRAIL in vitro on the gastric carcinoma cells. METHODS: The full-length cDNA of TRAIL was inserted into a vector under the control of the tetracycline-responsive element (TRE) to obtain the plasmid pRevTRE-TRAIL, which was transfected into a packaging cell line PT67. In addition, vector pRev-Tet On and pRevTRE were also transfected into PT67 separately. After hygromycin and G418 selection, the viral titer was determined. The medium containing retroviral vectors was collected and used to transduce a gastric carcinoma cell line NCI-N87. The resulting cell line NCI-N87-Tet On TRE-TRAIL and a control cell line, NCI-N87 Tet On-TRE, were established. TRAIL expression in the cell line was induced by incubating cells with doxycycline (Dox), which is a tetracycline analogue. The killing effect on gastric carcinoma cells was analyzed after induction. RESULTS: The recombinant plasmid pRev-TRE-TRAIL was constructed. After hygromycin or G418 selection, the producer cell lines PT67-TRE, PT67-TRE-TRAIL and PT67-Tet On were obtained, with titers of about 108 CFU·L-1. By transducing NCI-N87 cells with retroviral vectors from these cell lines, stable cell lines NCI-N87-Tet On TRE-TRAIL (NN3T) and control cell line NCI-N87-Tet On TRE (NN2T) were established. The growth curves of the selected cell lines were the same with the wild type NCI-N87. When Dox was added, cell death was obvious in the test groups (29%-77%), whereas no difference was observed in control and wild type cell lines. With the addition of a medium from the test group, human leukemia cell line Jurkat was activated till death (83%), indicating the secretion of active TRAIL proteins from the test cells to the medium. CONCLUSION: With the use of the RevTet-On system, a regulated expression system for TRAIL was constructed. Using this system, the selected killing effect of TRAIL on gastric carcinoma cell line NCI-N87 could be observed.

In order to carry out studies on structure and function relationships of porcine pepsinogen using site-directed mutagenesis approaches, the cDNA of this zymogen was cloned, sequenced, expressed in Escherichia coli, and the protein refolded, and purified to homogeneity. Porcine pepsinogen cDNA, obtained from a lambda gt10 cDNA library of porcine stomach contains 1364 base pairs. It contains leader, pro, and pepsin regions of 14, 44, and 326 residues, respectively. In addition, it also contains 5'- and 3'-untranslated regions. Four differences are present between the sequence deduced from the cDNA and the pepsinogen sequence determined previously by protein chemistry methods. Residues P19 (in the pro region) and 263 are asparagines in the cDNA sequence instead of aspartic acids. Isoleucine 230 is not present in the cDNA sequence and residue 242 is a tyrosine in the cDNA instead of an aspartic acid. Porcine pepsinogen cDNA was placed under the control of a tac promoter in a plasmid and expressed in E. coli. The synthesis of pepsinogen was optimized to about 50 mg/liter of culture. The recombinant (r-) pepsinogen, which was insoluble, was recovered by centrifugation, washed, dissolved in 6 M urea in Tris-HCl, pH 8, and refolded by rapid dilution. r-pepsinogen was purified to homogeneity after chromatography on Sephacryl S-300 and fast protein liquid chromatography on a monoQ column. r-pepsinogen contains an additional methionine residue at the NH2 terminus as compared to native (n-) pepsinogen. However, r- and n-pepsinogens are indistinguishable in their intramolecular activation constants. After activation, r- and n-pepsins have the same NH2-terminal sequences as well as Km values. Based on these data, r-pepsinogen was judged suitable for mutagenesis studies. A mutant pepsinogen (D32A) with the active site aspartic acid changed to an alanine was produced and purified. D32A-pepsinogen did not convert to pepsin in acid solution but it bound to pepstatin with an apparent KD of about 5 x 10(-10) M. D32A-pepsinogen possesses no detectable proteolytic activity. These results indicate that (i) intramolecular pepsinogen activation is accomplished by the pepsin active site, and (ii) unlike subtilisin (Carter, P., and Wells, J. A. (1988) Nature 332, 564-568), the active site mutant of pepsin is not enzymically active.