Objective To investigate the clinical efficacy, the toxicity and side reactions of interventional chemoembolization with FOLFOX4 regimen through both hepatic artery and superior mesenteric artery, i.e. dual access technique, in treating primary hepatocellular carcinoma. Methods Between November 2010 and March 2013 at authors’ hospital, a total of 21 patients with advanced primary hepatocellular carcinoma (the study group) were treated with FOLFOX4 regimen by using dual access interventional technique. FOLFOX4 regimen included hepatic arterial infusion of 5-fluorouracil 400 mg/m2, hepatic arterial chemoembolization with iodipin and oxaliplatin 85 mg/m 2, intravenous administration of calcium folinate 200 mg/m2 IV on the first and second day, trans-superior mesenteric artery continuous infusion (lasting for 22 hours) of 5 -Fuorouracil 600 mg/m2 on the first and second day. During the same period other 21 patients with primary hepatocellular carcinoma were selected (used as the control group) to receive conventional hepatic arterial chemoembolization. In both groups, the treatment was repeated after 4-6 weeks. The therapeutic effect and the toxicity and side reactions were evaluated after the second treatment. Results The effective rate for the study group and the control group was 61.9% and 28.6% respectively, and the median survival time for the study group and the control group was 14.7 months and 9.4 months respectively. The differences in the effective rate and the median survival time between the two groups were statistically significant (P = 0.030 and P = 0.034). The occurrence of toxicity and side reactions, such as digestive tract reactions and the damage of liver function, in the study group were strikingly lower than those in the control group. Conclusion Through dual approach of hepatic artery and superior mesenteric artery catheterization, interventional chemoembolization with FOLFOX4 regimen is outstandingly effective for primary hepatocellular carcinoma, meanwhile, the side effects are very slight.

BACKGROUNDRheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Many methods have been used to observe the progress of RA. The purpose of this study was to observe the progress of RA in rats with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the relationships among different methods in evaluation of RA.

METHODSSixteen healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA group and a control group. Bovine type II emulsified incomplete Freud's adjuvant was used to induce arthritis in the RA group. Arthritis score of the rats in two groups were recorded, and (18)F-FDG PET/CT, MR imaging were performed both on the corresponding rats every 3 days. All the rats were sacrificed at week 5, and histopathological examination was performed on rat knees stained with haematoxylin and eosin.

RESULTSThe arthritis score and the standard uptake value (SUV) of knee joints in RA rats increased with the progression of arthritis gradually. Both peaks of arthritis score and SUV appeared at 21 days after the first immune injection, then the arthritis score and SUV of knee joints decreased slowly. The arthritis scores of knee joints in RA rats were positively correlated with their SUV changes. The MR images were confirmed by the histopathological studies.

CONCLUSIONPET/CT can detect the earliest molecular metabolism changes of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all of which indicated that PET/CT and MR imaging may be applied as useful tools to monitor the progress of RA.

Animals ; Arthritis, Rheumatoid ; diagnosis ; pathology ; Fluorodeoxyglucose F18 ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Radiopharmaceuticals ; Rats ; Rats, Sprague-Dawley ; Tomography, X-Ray Computed

Objective: To compare the effects of various interventions on the incidence of central line-associated bloodstream infection (CLABSI) . Methods: The clinical data of 218 patients with central venous catheterization were retrospectively analyzed. Infected patients were treated as CLABSI group and non-infected patients as control group. Results: Of the 218 patients, 24 patients were developed CLABSI. There was no significant difference in sex, age, primary infection status and puncture site between CLABSI group and control group. Univariate analysis showed that axillary vein puncture could significantly reduce the incidence of CLABSI (P=0.028), and the infection rate of axillary vein puncture per 1000 days under B-ultrasound was significantly reduced by 0.93‰. The average indwelling days of deep venous catheter in patients with pulse puncture were significantly longer than those in other groups (47.32 days vs 19.90 days). The average indwelling days in patients with axillary vein puncture positioned by B ultrasound were longer than those in patients with other parts of vein puncture positioned by B ultrasound (P < 0.05). Logistic multiple regression analysis showed that the main risk factors for CLABSI were anatomically located puncture (P = 0.031) and non-axillary venous catheterization (P = 0.068). Conclusions Choosing axillary vein as the position of deep venous catheterization and using ultrasound-guided central venous puncture can reduce the incidence of CLABSI and prolong the average catheterization time.

OBJECTIVETo investigate the effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) mediated antiviral activity against hepatitis B virus (HBV) and duck hepatitis B virus (DHBV).

METHODSTotal RNA was extracted from peripheral blood mononuclear cells (PBMCs), RT-PCR product was cloned into the EcoR I/Hind III restriction sites of the CMV-driven expression vector fused with a hemagglutinin fusion epitope tag at its carboxyl terminal. Replication competent 1.3 fold over-length HBV was constructed with full-length HBV of ayw subtype. The mammalian hepatoma cell HepG2 was cotransfected with the replication competent 1.3 fold over-length HBV and various amounts of CMV-driven expression vector encoding APOBEC3G-HA. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA, HBV DNA. RNA from intracellular core particles was examined using Northern and Southern blot analyses. Chicken hepatoma cell LMH was cotransfected with head-to-tail dimer of an EcoR I monomer of DHBV and various amounts of CMV-driven expression vector encoding APOBEC3G-HA. DHBV DNA from intracellular core particles was examined using Southern blot analysis.

RESULTSCMV-driven expression vector encoding APOBEC3G-HA and replication competent 1.3 fold over-length HBV were constructed. There was a dose dependent decrease in the levels of intracellular core-associated viral (HBV and DHBV) DNA and extracellular production of HBsAg and HBeAg. Levels of intracellular core-associated viral RNA were also decreased, but the expression of HBcAg remained almost unchanged.

CONCLUSIONAPOBEC3G suppresses HBV and DHBV replication and also suppresses HBsAg and HBeAg expression.

APOBEC-3G Deaminase ; Cytidine Deaminase ; genetics ; Hep G2 Cells ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B Virus, Duck ; physiology ; Hepatitis B e Antigens ; metabolism ; Hepatitis B virus ; physiology ; Humans ; RNA, Messenger ; genetics ; Virus Replication

Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-β-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-β-D-glucopyranoside (8), luteolin-4'-0-β-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3β-0-acetate (10), darma-20, 24-dien-3β-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3β-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Inula ; chemistry ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVESTo study the effects of tumor suppressor in lung cancer-1 (TSLC1) on human hepatocyte carcinoma cell line HepG2.

METHODSA full length of TSLC1 cDNA was amplified from RNA of normal human liver cells by RT-PCR, and it was cloned into a pCI-neo expression vector and transfected into human hepatocellular carcinoma cell line HepG2. The HepG2 cells transfected with this plasmid (experimental group) and those treated with pCI-neo vector (control group) and without any treatment (blank group) were compared. Cell morphology was studied microscopically and cell growth was analyzed with MTT assay. FACSort flow cytometry analysis was performed to assess the cell cycle distribution and apoptosis.

RESULTSA stable cell line expressing TSLC1 protein was successfully established. Morphologically, cells of the experimental group were tightly aggregated when compared with those of the control and blank groups. The growth of TSLC1-transfected cells was significantly suppressed in vitro compared with those of the control and blank groups. The amount of G0-G1 cells was 63.66%+/-3.83% (P less than 0.01) in the experimental group, while those of the control and blank groups were 47.45%+/-0.91% and 54.47%+/-0.96% respectively. The amount of S phase cells in the experimental group, 22.90%+/-6.04%, was significantly lower (P less than 0.05) than that of the control group (36.58%+/-0.61%) and the blank group (33.61%+/-2.99%), which suggested a G0-G1 cell cycle arresting. The number of cells in early and late phase apoptosis (17.09%+/-0.20% and 16.11%+/-0.40% respectively) were significantly higher than those of the control and blank groups (P less than 0.01).

CONCLUSIONSTSLC1 strongly inhibits the growth of HepG2 cells in vitro and induces apoptosis of the cells, suggesting that TSLC1 may have a tumor suppressor function in HCC.

Apoptosis ; genetics ; Cell Adhesion Molecule-1 ; Cell Adhesion Molecules ; Cell Proliferation ; Hep G2 Cells ; Humans ; Immunoglobulins ; genetics ; Membrane Proteins ; genetics ; Transfection ; Tumor Suppressor Proteins ; genetics

Objective To analyze the factors which may affect postoperative patency of microsurgical vasoepididymostomy (VE).Methods Ninety-four patients underwent VEs from September 2014 to June 2016 in the Department of Urology,Peking University Third Hospital,with average age of (30.7 ± 4.8) years,and body mass index (BMI) of (25.1 ± 3.0) kg/m2.Semen analyses were performed 1 month,3 months and 5 to 6 months after the operation.The following semen analyses were performed every 3-6 months thereafter.Patency was defined by finding sperms in twice or more analyses during the followup until August 2017.Patients were followed up by face-to-face or telephone interview.Seven factors (age,BMI,bilateral or unilateral anastomosis,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid) were analyzed by Chi-square analysis and multifactor logistic regression analysis.Results Eighty-two patients were followed up (87.2％,82/94) while 12 patients were lost of follow-up.The mean follow-up time was 19 months.Sperms were found in the ejaculate in 59 patients postoperatively.The overall patency rate was 72.0％ (59/82),and natural paternity rate was 32.8％ (19/58).Patients ≤28 years old and those ＞28 years old had patency rates of 89.3％ (25/28) and 63.0％ (34/54,P =0.012),respectively.Patients with BMI ＜26.0 kg/m2 and BMI≥26.0 kg/m2 had patency rates of 80.4％ (41/51) and 58.1％ (18/31,P =0.029),respectively.Patency rate of bilateral surgery was 72.1％ (44/61) and of unilateral surgery was 71.4％ (44/62,P =0.727).Patency rate of caput anastomosis achieved 75.0％ (15/20) and of corpus/caudal anastomosis was 71.0％ (44/62,P =0.727).Patency rates of patients with and without adjustment of anastomosis sites were 77.8％ (7/9) and 71.2％ (52/73,P =0.680),respectively.Patency rates of a lot,a few,motile and seldom-motile sperms in epididymal fluid were 74.3％ (55/74) vs.50.0％ (4/8,P =0.146) and 70.0％ (28/40) vs.73.8％ (31/42,P =0.701),respectively.Multifactor logistic regression analysis showed that age was well associated with patency rate (OR=4.705,95％CI 1.181-18.742,P=0.028).Conclusions Age ≤28 years is an independent factor leading to higher patency rates.Patients with lower BMIs and younger could have higher patency rates.Factors of anastomosis sides,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid showed no statistical difference in patency rates.

Adaptive immunity is a critical component of the human immune system, playing an essential role in identifying antigens and orchestrating a tailored immune response. This review delves into the significant strides made in the development of epitope prediction tools, their integration into vaccine design, and their pivotal role in enhancing immunotherapy strategies. The review emphasizes the transformative potential of these tools in refining our understanding and application of immune responses. Adaptive immunity distinguishes itself from innate immunity by its ability to recognize specific antigens and remember past infections, leading to quicker and more effective responses upon subsequent exposures. This facet of immunity involves complex interactions between various cell types, primarily B cells and T cells, which recognize distinct epitopes presented by antigens. Epitopes are small sequences or configurations on antigens that are recognized by the immune receptors on B cells and T cells, acting as the focal points of immune recognition and response. Epitopes can be broadly classified into two types: linear (or sequential) epitopes and conformational (or discontinuous) epitopes. Linear epitopes consist of a sequence of amino acids in a protein that are recognized by B cells and T cells in their primary structure form. Conformational epitopes, on the other hand, are formed by spatially distinct amino acids that come together in the tertiary structure of the protein, often recognized by the immune system only when the protein folds into its native conformation. The role of epitopes in the immune response is critical as they are the primary triggers for the activation of B cells and T cells. When an epitope is recognized, it can stimulate B cells to produce antibodies, mobilize helper T cells to secrete cytokines, or prompt cytotoxic T cells to kill infected cells. These actions form the basis of the adaptive immune response, tailored to eliminate specific pathogens or infected cells effectively. The prediction of B cell and T cell epitopes has evolved with advances in computational biology, leading to the development of several sophisticated tools that utilize a variety of algorithms to predict the likelihood of epitope regions on antigens. Tools employing machine learning methods, such as support vector machines (SVMs), XGBoost, random forest, analyze large datasets of known epitopes to classify new sequences as potential epitopes based on their similarity to known data. Moreover, deep learning has emerged as a powerful method in epitope prediction, leveraging neural networks capable of learning high-dimensional data from vast amounts of immunological inputs to identify patterns that may not be evident to other predictive models. Deep learning models, such as convolutional neural networks (CNNs), recurrent neural networks (RNNs) and ESM protein language model have demonstrated superior accuracy in mapping the nonlinear relationships inherent in protein structures and epitope interactions. The application of epitope prediction tools in vaccine design is transformative, enabling the development of epitope-based vaccines that can elicit targeted immune responses against specific parts of the pathogen. These vaccines, by focusing the immune response on highly specific regions of the pathogen, can offer high efficacy and reduced side effects. Similarly, in cancer immunotherapy, epitope prediction tools help identify tumor-specific antigens that can be targeted to develop personalized immunotherapeutic strategies, thereby enhancing the precision of cancer treatments. The future of epitope prediction technology appears promising, with ongoing advancements anticipated to enhance the precision and efficiency of these tools further. The integration of broader immunological data, such as patient-specific immune profiles and pathogen variability, along with advances in AI and machine learning, will likely drive the development of more adaptive, robust, and clinically relevant prediction models. This will not only improve the effectiveness of vaccines and immunotherapies but also contribute to our broader understanding of immune mechanisms, potentially leading to breakthroughs in the treatment and prevention of multiple diseases. In conclusion, the development and refinement of epitope prediction tools stand as a cornerstone in the advancement of immunological research and therapeutic design, highlighting a path toward more precise and personalized medicine. The ongoing integration of computational models with experimental immunology holds the promise of revolutionizing our approach to combating infectious diseases and cancer.

OBJECTIVETo determine the value of elective neck dissection in patients with clinically stage I (cT1N0M0) squamous cell carcinoma of the tongue.

METHODSThis was a retrospective study of patients with surgical treatment between November 1984 and November 1999. A total of 130 patients were included in the study, all of whom received operation of the primary site, meanwhile, 99 of whom underwent elective neck dissection simultaneously including level I -III or level I -IV neck dissection in 20 patients and level I - V neck dissection in 79 patients. Results Among all these patients, the rate of occult metastasis to the neck were 12. 0%. Local failure rate in patients with only local treatment, level I II, II, III/IV neck dissection and level I - V neck dissection were 25. 8%, 15. 0% and 7. 6% respectively. There were significant difference in regional failure between patients with only local treatment and patients with elective neck dissection (P < 0.05). Also, no significant differences were noted in the survival rate between patients with only local treatment, elective neck dissection (level I -III or level I -IV) and level I -V neck dissection (P > 0.05).

CONCLUSIONSElective neck dissection significantly reduced regional control failure but was not able to reduce distant metastasis or increase the overall survival. A prospective randomized study is worthwhile to further evaluate the benefit of elective neck dissection in the treatment of clinically stage I squamous cell carcinoma of the tongue.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; surgery ; Elective Surgical Procedures ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck Dissection ; Neoplasm Staging ; Retrospective Studies ; Tongue Neoplasms ; pathology ; surgery ; Treatment Outcome ; Young Adult

Laser induced breakdown spectroscopy ( LIBS ) was proposed to rapidly discriminate microbe species. Ten species of microbes were prepared in lab. Filter papers were selected as substrate for enriching bacteria and enhancing the quality of LIBS. The images of plasma were collected by ICCD camera and LIBS spectra were obtained by spectrometers. The results displayed that the images and spectra were different from 10 bacteria. It was demonstrated that this method was feasible to discriminate bacteria species by analyzing image and/or spectroscopy. Furthermore, nine smooth and multiple scattering correction ( MSC) were utilized to preprocess the LIBS full-spectrum data in the wavelength range of 200-420 nm and 560-680 nm. And principal component analysis ( PCA) and PCA-RF ( Random forest) were compared to validate the accuracy of discrimination. The investigation showed that the PCA-RF model coupled with suitable methods in preprocessing data could identify bacteria. The accuracy was 99. 6% for ten species of microbes by evaluating LIBS spectra in training set, and 96. 7% in predicting set. This report indicated that it is feasible to differentiate bacteria species by analyzing LIBS spectra.