Role of minimally invasive techniques in gastrointestinal surgery: Current status and future perspectives.

In recent years, the incidence of gastrointestinal cancer has remained high. Currently, surgical resection is still the most effective method for treating gastrointestinal cancer. Traditionally, radical surgery depends on open surgery. However, traditional open surgery inflicts great trauma and is associated with a slow recovery. Minimally invasive surgery, which aims to reduce postoperative complications and accelerate postoperative recovery, has been rapidly developed in the last two decades; it is increasingly used in the field of gastrointestinal surgery and widely used in early-stage gastrointestinal cancer. Nevertheless, many operations for gastrointestinal cancer treatment are still performed by open surgery. One reason for this may be the challenges of minimally invasive technology, especially when operating in narrow spaces, such as within the pelvis or near the upper edge of the pancreas. Moreover, some of the current literature has questioned oncologic outcomes after minimally invasive surgery for gastrointestinal cancer. Overall, the current evidence suggests that minimally invasive techniques are safe and feasible in gastrointestinal cancer surgery, but most of the studies published in this field are retrospective studies and case-matched studies. Large-scale randomized prospective studies are needed to further support the application of minimally invasive surgery. In this review, we summarize several common minimally invasive methods used to treat gastrointestinal cancer and discuss the advances in the minimally invasive treatment of gastrointestinal cancer in detail.

CD4+ T cell depletion does not affect the level of viremia in chronically SHIVSF162P3N-infected Chinese cynomolgus monkeys.

Chronically SHIVSF162P3N-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4+ T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4+ T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection.

Postoperative complications after robotic resection of colorectal cancer: An analysis based on 5-year experience at a large-scale center.

BACKGROUND: As a common gastrointestinal malignancy, colorectal cancer (CRC) poses a serious health threat globally. Robotic surgery is one of the future trends in surgical treatment of CRC. Robotic surgery has several technical advantages over laparoscopic surgery, including 3D visualization, elimination of the fulcrum effect, and better ergonomic positioning, which together lead to better surgical outcomes and faster recovery. However, analysis of independent factors of postoperative complications after robotic surgery is still insufficient. AIM: To analyze the incidence and risk factors for postoperative complications after robotic surgery in patients with CRC. METHODS: In total, 1040 patients who had undergone robotic surgical resection for CRC between May 2015 and May 2020 were analyzed retrospectively. Postoperative complications were categorized according to the Clavien-Dindo (C-D) classification, and possible risk factors were evaluated. RESULTS: Among 1040 patients who had undergone robotic surgery for CRC, the overall, severe, local, and systemic complication rates were 12.2%, 2.4%, 8.8%, and 3.5%, respectively. Multivariate analysis revealed that multiple organ resection (P < 0.001) and level III American Society of Anesthesiologists (ASA) score (P = 0.006) were independent risk factors for overall complications. Multivariate analysis identified multiple organ resection (P < 0.001) and comorbidities (P = 0.029) as independent risk factors for severe complications (C-D grade III or higher). Regarding local complications, multiple organ resection (P = 0.002) and multiple bowel resection (P = 0.027) were independent risk factors. Multiple organ resection (P < 0.001) and level III ASA score (P = 0.007) were independent risk factors for systemic complications. Additionally, sigmoid colectomy had a lower incidence of overall complications (6.4%; P = 0.006) and local complications (4.7%; P = 0.028) than other types of colorectal surgery. CONCLUSION: Multiple organ resection, level III ASA score, comorbidities, and multiple bowel resection were risk factors for postoperative complications, with multiple organ resection being the most likely.

Clinical and MRI response to dose reduction of an etanercept-biosimilar for hip arthritis in patients with ankylosing spondylitis: an observational, retrospective cohort study.

OBJECTIVES: Hip arthritis plays a critical role in the prognosis of ankylosing spondylitis (AS). Dose reduction of tumor necrosis factor inhibitors preserves general improvement of AS, so this study attempted to examine the equivalence between Yisaipu® tapering and conventional therapy for hip arthritis in AS patients, using clinical parameters and magnetic resonance image (MRI). METHODS: AS patients received this etanercept-biosimilar injections (50 mg/week) in the first 12 weeks. Participants in the tapering group were treated with this reagent 50 mg every other week from week 13 to week 24, while the control group kept undergoing full-dose therapy. Clinical and laboratory parameters were assessed at baseline, week 12 and week 24. MRI examination of hip was performed at baseline and week 24. RESULTS: One hundred and thirty-six patients were enrolled, and 80 of them were in the tapering group. Linear mixed model revealed that main effects of tapering group with control group as reference in disease activity parameters were insignificant (p > 0.05). Main effects of baseline with week 24 as reference were significant (p < 0.05), but main effects of week 12 with week 24 as reference were not (p > 0.05). Prevalence of acute inflammatory change in MRI significantly decreased in the tapering group (76.88% vs 20.00%, p < 0.05) and control group (76.79% vs 19.64%, p < 0.05). Influence of both treatments on acute inflammatory change was equivalent (p > 0.05). CONCLUSION: Efficacy of Yisaipu® tapering treatment is comparable to the full-dose therapy for hip arthritis in AS patients. Both treatments maintain remission of hip arthritis after patients achieved low disease activity.

Flexible and Accurate Simulation of Radiation Cooling with FETD Method.

Thermal management and simulation are becoming increasingly important in many areas of engineering applications. There are three cooling routes for thermal management, namely thermal conduction, thermal convection and thermal radiation, among which the first two approaches have been widely studied and applied, while the radiation cooling has not yet attracted much attention in terrestrial environment because it usually contributes less to the total amount of thermal dissipation. Thus the simulation method for radiation cooling was also seldom noticed. The traditional way to simulate the radiation cooling is to solve the thermal conduction equation with an approximate radiation boundary condition, which neglects the wavelength and angular dependence of the emissivity of the object surface. In this paper, we combine the heat conduction equation with a rigorous radiation boundary condition discretized by the finite-element time-domain method to simulate the radiation cooling accurately and flexibly. Numerical results are given to demonstrate the accuracy, flexibilities and potential applications of the proposed method. The proposed numerical model can provide a powerful tool to gain deep physical insight and optimize the physical design of radiation cooling.

The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. Lack of effective pharmacotherapies for NASH is largely attributable to an incomplete understanding of its pathogenesis. The deubiquitinase cylindromatosis (CYLD) plays key roles in inflammation and cancer. Here we identified CYLD as a suppressor of NASH in mice and in monkeys. CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity. We observed that overexpression of Cyld in hepatocytes concomitantly inhibits lipid accumulation, insulin resistance, inflammation and fibrosis in mice with NASH induced in an experimental setting. Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. Notably, reconstitution of hepatic CYLD expression effectively reverses disease progression in mice with dietary or genetically induced NASH and in high-fat diet-fed monkeys predisposed to metabolic syndrome. Collectively, our findings demonstrate that CYLD mitigates NASH severity and identify the CYLD-TAK1 axis as a promising therapeutic target for management of the disease.

Chiral copper(II) complex based on natural product rosin derivative as promising antitumour agent.

To evaluate the biological preference of chiral drug candidates for molecular target DNA, the synthesis and characterization of a chiral copper(II) complex (2) of a chiral ligand N,N'-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral, emission spectral and viscosity analysis reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. In the absence/presence of ascorbic acid, 1 and 2 cleaved supercoiled pBR322 DNA by single-strand and 2 displayed stronger DNA cleavage ability. In addition, in vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines study show that they exhibited effective cytotoxicity against the tested cell lines, notably, 2 showed a superior cytotoxicity than the widely used drug cisplatin under identical conditions, indicating it has the potential to act as effective anticancer drug. Flow cytometry analysis indicates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis demonstrates that 2 mainly arrested HeLa cells at the S phase. The study represents the first step towards understanding the mode of the promising chiral rosin-derivative based copper complexes as chemotherapeutics.

[Efficacy of local injection of RhTNFR: Fc in collagen-induced arthritis of rats].

OBJECTIVE: To evaluate the efficacy of recombinant human tumor necrosis factor-α receptor II: IgG fusion protein (RhTNFR:Fc) local injection in collagen-induced arthritis (CIA) of rats. METHODS: Twenty-four CIA rats were randomly divided into 3 groups: single therapy (Group I), multiply therapies (Group II) and control (Group III). Group I received normal saline thrice after a single RhTNFR:Fc local treatment while Groups II and III had 4 times of RhTNFR:Fc or normal saline local injection. The severities of right ankle and systemic inflammation were assessed by arthritis index (AI) at baseline and every week after local injection (visits 1, 2, 3 and 4). Serum C reactive protein (CRP) was measured after the last visit. And right ankles were further examined through radiology and pathology. RESULTS: Local or systemic AI of Group I were significantly lower than that of baseline at visit 1 (P < 0.05), but increased during other visits. And local or systemic AI of Group II gradually decreased at each follow-up, but AI of Group III showed no decline. The radiographic scores (5.70±0.67 and 4.90±0.73), histopathological scores (6.00±0.67 and 3.80±0.91) and serum CRP concentration (7.50±0.87 and 3.09±0.76 µg/ml) of Group I and Group II were lower than those of Group III (6.60±1.26, 7.10±0.7 and 12.15±3.47 µg/ml, P < 0.05). And all these parameters of Group I were higher than those of Group II (P < 0.05). CONCLUSION: Local injection of RhTNFR:Fc can effectively alleviate disease activity of CIA and reduce CRP concentration, radiographic and histopathological scores. Multiple therapies show a better efficacy than single injection.

Azithromycin inhibits neutrophil accumulation in airways by affecting interleukin-17 downstream signals.

BACKGROUND: Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases. However, the precise mechanism behind this action remains unknown. Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 (IL-17) downstream signals. METHODS: Mice were pretreated with azithromycin before murine IL-17A (mIL-17) stimulation. After the mIL-17 stimulation, the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay (ELISA) tests in bronchoalveolar lavage (BAL) fluid; IL-6, CXC chemokine ligand-1 (CXCL-1), CXCL-5, macrophage inflammatory protein-2 (MIP-2), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF). The number of neutrophils in BAL fluid were evaluated by cytospin preparations. RESULTS: (1) Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines (MIP-2, CXCL-5 and GM-CSF) and the accumulation of neutrophils in airways caused by mIL-17 stimulation. (2) The levels of three neutrophil-mobilizing cytokines (IL-6, MIP-2 and GM-CSF) were positively correlated with the numbers of neutrophil in BAL fluid. CONCLUSIONS: Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals. This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.

[Establishment and evaluation of a Chinese rhesus model of tuberculosis].

OBJECTIVE: To establish and evaluate the Chinese rhesus model of tuberculosis. METHODS: Twelve Chinese rhesus macaques, randomly divided into 3 groups, were inoculated with 2 different doses of Mycobacterium tuberculosis H(37) Rv strain via both bronchoscopic and intratracheal instillation into the lungs. Clinical observation and laboratory examinations were performed, including erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test and X-ray examination. Histopathological assessments were performed in the 24th week postinfection. Statistical analysis was performed by ANOVA in the 3 groups. RESULTS: After infection all the animals manifested fever, weight lose, lack of appetite, coughing and other symptoms of tuberculosis. The temperature gradually increased and reached a peak [(40.1 ± 0.2)°C] at the 8th week postinfection. The weight decreased significantly at 24th week postinfection (-5.5 ± 5.6)%. Erythrocyte sedimentation rate elevated significantly at the 6th to 8th week postinfection (36 ± 40) mm/1 h. C-reactive protein was significantly increased at the 6th to 24th week after infection (75.8 ± 49.8) mg/L. The positive rate of tuberculin skin test was 100%. In Group I (bronchoscopic instillation, 20 CFU) the disease developed slowly, and the main manifestation of chest X-ray was patchy shadows. In group II (bronchoscopic instillation, 100 CFU) and group III (intratracheal instillation, 100 CFU) the disease developed rapidly, and the main manifestation of chest X-ray was patchy and nodular lesions during the 4th to the 12th week postinfection, but became large patchy and consolidation lesions during the 12th to the 24th week postinfection. Tuberculosis granuloma and caseous necrosis, similar to the pathological changes of human tuberculosis, were found in the lungs, mediastinal lymph nodes, kidney and spleen. The results of acid-fast stain were positive. The most serious pathological manifestations were observed in group II, followed by group III and group I. The highest bacterial load of the right lung was seen in group II, followed by group I and group III. CONCLUSIONS: A chinese rhesus model of tuberculosis was successfully developed via both bronchoscopic and intratracheal instillation. Their clinical manifestations, disease progression and pathological changes were similar to human primary tuberculosis and hematogenous disseminated tuberculosis.