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OBJECTIVE: To investigate the effect of tacrolimus on the proliferation of fibroblasts after glaucoma surgery. MATERIALS AND METHODS: Biopsy was applied in this study. Under aseptic conditions, tissues were collected from rabbits, cut into small pieces and cultured. Morphology of fibroblasts was observed under a microscope. Features of fibroblasts were identified via immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Western blotting and RT-PCR were performed to detect the expressions of related proteins after treatment. Flow cytometry and cell counting kit-8 (CCK-8) assay were employed to examine the proliferation of human Tenon's capsule fibroblasts (HTFs) after tacrolimus treatment. RESULTS: Tacrolimus decreased the levels of survivin and α-smooth muscle actin (α-SMA) after transforming growth factor-β (TGF-β) treatment. Besides, it inhibited proliferation and induced apoptosis of HTFs. CONCLUSIONS: Tacrolimus reduces proliferation and promotes apoptosis of HTFs by inhibiting the expression of survivin, which may be a strategy for treating hypertrophic scar after glaucoma surgery. [ABSTRACT FROM AUTHOR]

Let R be a ring, G an ordered group and a a map from G into the group of automorphisms of R. If R is reduced, then the Malcev-Nemnann ring R * ((G)) has the same triangulating dimension as R. Furthermore, if R is a PWP ring, then so is R * ((G)). [ABSTRACT FROM AUTHOR]

This article focuses on the wide band voltage-controlled oscillator (VCO) with a frequency range from 830 MHz to 2.4 GHz. The VCO has two control inputs, one for continuous control of the output frequency and one for band switching and two quadrature outputs. This VCO is simulated for the supply voltage of 2V. A wide tuning range of 98% is obtained in two independent bands. The harmonic distortions are kept low enough within the entire frequency range. The phase noise is 105 dBc/Hz at 400 kHz offset for the oscillation frequency of 830 MHz, and is 89 dBc/Hz at 400 kHz offset for the oscillation frequency of 2.42 GHz. Accurate quadrature outputs are maintained throughout the entire frequency range, as needed in all modem transceiver architectures.

The SHS reaction in the Ni-Ti-B4C system starts with the formation of Ni-Ti and Ni-B intermetallic compounds from the solid interacted reaction among the reactants and, subsequently, the formation of Ni-Ti and Ni-B liquid at the eutectic point. Meanwhile, some C atoms from the reaction between Ni and B4C can dissolve into Ni-Ti liquid to form TiC. The heat generated from these reactions can promote the mutual diffusion of Ni-Ti-C and Ni-B liquid and simultaneously accelerate the formation of Ni-Ti-C-B liquid. Finally the precipitation of TiC and TiB2 occur when the C and B atoms in the liquid become supersaturated. The addition of Ni not only promotes the occurrence of the self-propagating high temperature synthesis (SHS) reaction by forming Ni-Ti liquid, but also accelerates the SHS reaction by forming Ni-B liquid and dissociative C. The early appearance of dissociative C from the reaction between Ni and B4C causes the formation of TiC prior to that of TiB2. [ABSTRACT FROM AUTHOR]

Influenza is a contagious respiratory disease caused by influenza viruses, and the burden of severe disease is commonly seen in high risk populations. Influenza vaccination is an effective way to prevent influenza and its complications, especially for high risk populations. Although some countries have included influenza vaccine in their national immunization programs, influenza vaccination rates remain low globally in high risk populations. The influenza vaccine in China is still a non-immunization program vaccine that is voluntarily vaccinated at its own expense, and the influenza vaccine immunization strategy is different across the country. There is still a gap between the vaccination rate of the influenza vaccine and that of developed countries. It is an urgent problem to further optimize the whole population immunization strategy of influenza vaccine in China, strengthen the publicity of the whole population immunization strategy of influenza vaccine, and reduce the disease burden of influenza in China.

Vaccination is the most cost-effective measure to prevent infectious diseases in both children and adults. At present, the global burden of infectious diseases in adults is still heavy. With the continuous development and improvement of vaccines, vaccination has shown great potential to prevent infectious diseases, further reduce the morbidity and mortality of infectious diseases in adults and improve people's life quality. This article summarizes the current status of adult immunization, immunization strategies of representative countries, different adult vaccination strategies, and the advantages and challenges of adult immunization to provide reference for further exploring adult immunization strategies and improving adult vaccination recommendations. More attention should be paid to the immunization strategies for different adult populations, and effective measures should be taken to improve the vaccination coverage for the better protection of people's life and health.

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P =0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P =0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC ( P >0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P =0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Objective: To examine the influence factors of short-term recurrence after complete surgical resection of retroperitoneal liposarcoma. Methods: The clinicopathological data of retroperitoneal liposarcoma at Department of General Surgery, the First Medical Center, People's Liberation Army General Hospital from January 2000 to January 2020 were retrospectively analyzed. There were 60 males and 31 females, aged (52.1±9.9) years (range: 30 to 84 years). Tumor recurrence within 12 months after complete resection was defined as short-term recurrence, and tumor recurrence more than 12 months was defined as non-short-term recurrence. The t test, rank-sum test, χ 2 test and Fisher exact test were conducted for inter-group comparison. Logistic regression analysis was used to analyze the independent influence factors for the short-term recurrence of retroperitoneal liposarcoma after complete resection. The Kaplan-Meier curve was used to calculate the recurrence-free survival, and the Log-rank test was adopted for the comparison between the groups. Results: The univariate analysis results showed that irregular tumor morphology, multiple pathological subtypes, pathological scores>3, and multiple primary tumors are influence factors for short-term recurrence after complete resection of retroperitoneal liposarcoma (χ 2 : 4.422 to 7.773, all P <0.05). Regression analysis of the above risk factors showed that multiple primary tumors was the independent risk factor ( OR =2.918, 95% CI : 1.127 to 7.556, P =0.027). In the short-term recurrence group, Kaplan-Meier curve analysis showed that patients with multiple primary tumors had a shorter median recurrence time than patients with unifocal tumor (6 months vs. 9 months, P= 0.028). Conclusions: Multiple primary tumor is an independent risk factor for short-term recurrence after complete resection of retroperitoneal liposarcoma. It suggests that the frequency of follow-up after surgery should be increased for such patients.

Objective: To study the expression of ALK protein in pulmonary adenocarcinoma as detected by Ventana immunohistochemistry, with correlation of clinicopathologic features., Methods: Immunohistochemical study for ALK protein using Ventana ALK (D5F3) kit was carried in 7 371 pulmonary adenocarcinoma samples. The clinicopathologic features were subsequently analyzed., Results: ALK fusion protein was detected in 446 of the 7 371 lung adenocarcinoma samples studied (6.05%). The ALK positivity rate in small biopsy samples was higher than that in surgical specimens [9.02% (153/1 696) versus 5.16% (293/5 675); P<0.01]. ALK fusion protein expression correlated with patient age, sample type and smoking history. ALK positivity rate in each age group increased with younger patient age. ALK positivity rate was 45.45% (10/22) in patients younger than 30 years old. The positivity rate of ALK fusion protein in adenocarcinoma in-situ, minimally invasive adenocarcinoma and invasive adenocarcinoma was 0, 0.48% (2/418) and 5.63% (291/5 165), respectively. The differences of ALK positivity rate amongst different subtypes had statistical significance (P<0.01). Invasive mucinous adenocarcinoma had highest ALK positivity rate, followed by invasive adenocarcinoma with predominantly solid pattern., Conclusions: ALK fusion protein is more often found in young patients with pulmonary adenocarcinoma, especially in those younger than 30 years old. ALK fusion protein is rarely expressed in early-stage pulmonary adenocarcinoma. Invasive mucinous adenocarcinoma and invasive adenocarcinoma with solid pattern have higher ALK positivity rate than other adenocarcinoma subtypes.

Medical pathogens induce infections, illnesses and sometimes serious medical conditions in the infected hosts. Diagnosis of these pathogens is important for proper treatment and investigation of pathogenesis processes. Molecular techniques have been developed for facilitating accurate, sensitive and low-cost diagnosis of these pathogens. Based on these techniques, diagnostic devices have been developed for a number of pathogens. More devices are needed for comprehensive coverage of medical pathogens. To facilitate the development of these devices, a database with integrated information about diagnostic methods, targets, and primers/probes for the known bacterial, fungal and viral pathogens is needed. We developed the microbial pathogen diagnostic methods database MicrobPad MD (http://bidd.nus.edu.sg/group/MicrobPad/MicrobPad.asp or http://pha-bidd.nus.edu.sg/group/MicrobPad/MicrobPad.asp) to provide comprehensive information about the molecular diagnostic techniques, targets, primers/probes, detection procedures and conditions, and tested diagnostic accuracies and limit of diagnosis for 314 bacterial, fungal and viral species from 61 genera. While available, additional information such as pathogen strains and hosts, tissue distribution or habitats, cultivation methods, biochemical characteristics, virulence factors, morphology, diseases, symptoms, treatment and prevention methods are provided. Our Database covers 242 gene targets, 700 primers/probes, 340 virulence factors, and 261 diseases. Cross-links to the NCBI genome and SwissProt/UniProt databases are provided., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Expression of a prion-like protein, doppel, induces apoptosis-like changes in cerebellar neuronal granule and Purkinje cells of prion-knockout mice and this effect can be rescued by re-introduction of cellular prion. Since most of those studies were done in transgenic mice, in the present study, we have established a murine neuro-2a cell line and the primary rat adult reactive astrocyte model for studying doppel-induced apoptosis and possible prion counteraction. We demonstrate that expression of doppel in neuro-2a cells causes apoptosis, during which DNA fragmentation occurs as visualized by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and other intracellular changes characteristic of apoptosis are observed in the electron microscope. Using immunoblot analyses, we further demonstrate that doppel expression activates caspase-10 as well as caspase-3, but does not activate caspase-9. Addition of purified doppel to cultures of neuro-2a cells and the primary astrocytes causes similar apoptotic changes. Significantly, apoptosis induced by doppel is enhanced when cellular prion protein is depleted by RNA interference, suggesting a protective effect of cellular prion against doppel-induced apoptosis. The antagonistic interaction between cellular prion and doppel appears to involve direct protein-protein interaction possibly on cell membrane as cellular prion and doppel physically interact with each other and co-localize on cell membranes. Together, our data show that doppel induces apoptosis in neuroblastoma neuro-2a and rat primary astrocytes via a caspase-10 mediated pathway and that this effect is counteracted by cellular prion through direct interaction with doppel possibly on cell membrane.

Conversion of normal cellular prion protein to the diseased form plays an essential role in transmissible spongiform encephalopathies such as mad cow disease and Creutzfeldt-Jakob disease. However, the normal physiological function of prion protein remains elusive. Doppel, a German synonym of double, was initially identified as a prion-like protein due to its structural and biochemical similarities. However, emerging evidence suggests that function of prion protein is more antagonistic to Doppel than synergistic. In this review, basic biochemical and structural similarities of prion protein and Doppel are introduced; evidence demonstrating antagonistic interaction of prion protein with Doppel is presented; and a potential novel activity of Doppel and prion protein in spermatogenesis, which could stimulate new avenues for research, is discussed.