Objective To investigate the relationship between blood vessel invasion (BVI) and clinicopathologic features and prognosis in patients with gastric cancer,and analyze related factors affecting the prognosis of patients.Methods The clinicopathological data of 206 patients with gastric cancer who were admitted to the Nanjing Hospital Affiliated to Nanjing Medical University from January 2007 to December 2010 were retrospectively analyzed.The BVI of surgical tumor specimens in all patients was detected by immunohistochemical staininng.All the patients were followed up via outpatient examination and telephone interview up to March 2014.The count data were analyzed using the chi-square test.The survival curve was drawn by Kaplan-Meier method.The survival analysis and univariate analysis were done using the Log-rank test,and multivariate analysis was done using the COX regression model.Results The BVI rate of 206 patients was 27.67％ (57/206).The BVI rate of tumor tissues,tumor differentiation,perineural invasion,T stage,N stage and TNM stage in all patients with gastric cancer were compared,showing significant differences (x2=14.396,9.569,15.579,43.453,30.732,P ＜ 0.05).After operation,188 patients were followed up for 6.0-60.0 months (median,34.0 months),with the follow-up rate of 91.26％ (188/206).Among 188 patients with follow-up,the median survival time and 5-year cumulative survival rate in patients with BVI and with negative BVI were 32.4 months and 19.6％,40.7 months and 42.0％,respectively,with a significant difference in the survival of patients (x2 =9.364,P ＜ 0.05).The results of univariate analysis showed that the diameter of tumor,tumor differentiation,perineural invasion,BVI,T stage,N stage and TNM stage were factors affecting the prognosis of patients with gastric cancer (x2=9.241,17.486,11.243,9.364,27.666,216.745,49.887,P ＜ 0.05).The results of multivariate analysis showed that the diameter of tumormore than 5 cm,BVI,stage T4,stage N3 and stage Ⅲ were independent risk factors affecting the prognosis of patients with gastric cancer (HR =0.502,0.456,0.052,0.001,0.735; 95％ confidence interval:0.334-0.754,0.289-0.720,0.004-0.664,0.000-0.006,0.159-3.398,P ＜ 0.05).Conclusions BVI in patients with gastric cancer is associated with the progression of tumors.The diameter of tumor more than 5cm,BVI,stage T4,stage N3 and stage Ⅲ are independent risk factors affecting the prognosis of patients with gastric cancer,and BVI may be a predictor of poor prognosis of patients with gastric cancer.

Autophagy constitutes a major catabolic hub for the quality control of intracellular entities of eukaryotic cells, and is emerging as an essential part of the host antiviral defense mechanism. However, in turn, viruses have evolved elegant strategies to co-opt various stages of the cellular autophagy pathway to establish virulence in vivo. This is particularly the case in the ubiquitous and persistent herpesvirus infection. In this review, I will focus on recent findings regarding the crosstalk between the herpes virus family and the autophagy pathway, with a look at the molecular mechanisms they use to disturb cells' autophagy regulation and eventually result in persistence and pathogenesis.
Autophagy ; Eukaryotic Cells ; Herpesviridae Infections ; Humans ; Immunity, Innate ; Quality Control ; Viruses

Objective To investigate the features and characteristics of GLIS3 gene mutation in patients with congenital hypothyroidism(CH),and to establish the theoretical basis for gene diagnosis and prenatal diagnosis of CH.Methods Genomic DNA was extracted from peripheral blood leukocytes of 50 patients with CH who were collected from February 2007 to November 2016 in Shandong Province.The exon 2 to 11 of GLIS3 were amplified with 11 pairs of sequence specific primers designed by Primer 5.0.Polymerase chain reaction and the first generation of sequencing method(Sanger sequencing) were used to detect the mutation.Comparison of the sequencing results with the GLIS3 reference sequence (National Center for Biotechnology Information Reference Sequence:NC_000009.12) helped to screen gene mutations.Results The 50 CH patients included 22 boys and 28 girls,and the sex ratio was 1.0 ∶ 1.3.The mean age was (2.5 ± 0.5) years.Six cases (12％) had thyroid gland hypoplasia,23 cases (46％) had thyroid gland agenesis and 21 cases(42％) with ectopic thyroid gland.C2507A missense mutation was found in exon 10 of GLIS3 in a thyroid gland agenesis case,which might result in proline to glutamine substitution at codon 836.One mutant (rs780019691,c.C289T) was detected which was nonsense mutation (Arg→Stop) in another thyroid gland agenesis child.Conclusions The mutation rate of GLIS3 gene is very low in CH children of Shandong province.Further studies are needed to investigate the relationship between GLIS3 genotypes and clinical phenotypes.

Objective To investigate the effects of laryngeal mask airway combined with lung-protective ventilation on postoperative pulmonary complications in patients undergoing open abdominal surgery with general anesthesia.Methods Eighty-seven patients of both sexes,aged 18-64 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective open abdominal surgery under general anesthesia,were randomly divided into 2 groups:endotracheal intubation plus routine ventilation group (group IC,n =43) and laryngeal mask airway plus protective ventilation group (group LP,n =44).In group IC,single lumen endotracheal tube was inserted and the patients were mechanically ventilated,with inhaled pure oxygen 2 L/min,tidal volume 8-10 ml/kg,respiratory rate 8-12 breaths/min,inspiratory/expiratory ratio 1 ∶ 2.In group LP,the ProSeal laryngeal mask airway was inserted and lung-protective ventilation was performed,with inhaled pure oxygen 2 L/min,tidal volume 6-8 ml/kg,respiratory rate 12-16 breaths/min,inspiratory/expiratory ratio 1 ∶ 2,positive end-expiratory pressure 5 cm H2O,and recruitment maneuvers was performed manually every 30 min during operation.End-tidal pressure of carbon dioxide was maintained at 35-45 mmHg.The development of pulmonary complications such as pneumonia,pleural effusion,pulmonary atelectasis,pneumothorax,bronchospasm and acute respiratory failure was recorded within 7 days after surgery.Results Pulmonary atelectasis,pneumothorax or acute respiratory failure was not found in the two groups.Compared with group IC,no significant change was found in the incidence of pneumonia,pleural effusion and bronchospasm after operation (P＞0.05),and the total incidence of postoperative pulmonary complications was significantly decreased in group LP (P＜0.05).Conclusion Compared with endotracheal intubation and conventional ventilation,laryngeal mask airway combined with lung-protective ventilation can reduce postoperative pulmonary complications in the patients undergoing open abdominal surgery with general anesthesia.

OBJECTIVETo study the prevention of colorectal cancer liver metastasis by adenoviral transduction of the endostatin gene.

METHODSThe recombinant adenovirus expressing endostatin was constructed. Its biological activities were surveyed in vitro, as determined in human umbilicus vein endothelium cell (HUVEC) proliferation inhibition, and in vivo, by reduction of liver metastasis.

RESULTSHUVEC proliferation was obviously inhibited by the infecting supernatant of recombinant adenovirus. Persistent high serum levels of endostatin in peripheral blood, especially in the liver vein were observed. The production of liver metastasis was intervened.

CONCLUSIONSThe single injection in the vein of the recombinant adenovirus realizes the high effective and stable expression of endostatin in general body and liver, which brings about the ideal prevention of liver metastasis.

Adenoviridae ; genetics ; Animals ; Cell Division ; drug effects ; Collagen ; genetics ; therapeutic use ; Colorectal Neoplasms ; pathology ; Disease Models, Animal ; Endostatins ; Endothelium, Vascular ; drug effects ; pathology ; Genetic Therapy ; Genetic Vectors ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis ; prevention & control ; Neoplasm Transplantation ; Peptide Fragments ; genetics ; therapeutic use ; Transduction, Genetic

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

OBJECTIVETo investigate the antiatherogenic effect and possible mechanisms of the extracts of Radix Salviae Miltiorrhizae (RSM) or Fructus Crataegi (FC), as well as their interaction.

METHODWistar rats were randomly divided into 2 groups: normal group and model group. The atherosclerotic model rats were injected VD3 and ovalbumin, while fed with high cholesterol diet. After the model was determined successfully, all model rats were divided into normal group, model group, Xuezhikang group, RSM group, FC group, mixture of RSM and FC group. Each group was given the corresponding drugs for 4 weeks. After 12 weeks, blood serum were analyzed for total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), superoxide dismutase ( SOD), malondialdehyde (MDA) and nitric oxide (NO). And the blood plasma also analyzed for levels of endothelin (ET), 6-keto prostaglandin F1alpha (6-keto-PGF1alpha), thromboxane B2 (TXB2), C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and so on. At last, the pathological observation of aorta was carried out.

RESULTCompared with those in model group, the TC, TG, LDL-C, ET, TXB2 and MDA levels and TXB2/PGF1alpha ratio were reduced, while the HDL-C, the serum SOD, No and 6-keto-PGF1alpha level were raised in the intervention groups. Although the levels of CRP, IL-6 and IL-8 were lower than model group, there was no obvious effect on the releasing of TNF-alpha.

CONCLUSIONRSM and FC could inhibit the atherogenesis formation and development, which might be due to regulating the lipid metabolism, enhancing the antioxidation, and reducing the release of inflammatory factors.

Animals ; Atherosclerosis ; prevention & control ; C-Reactive Protein ; analysis ; Crataegus ; Disease Models, Animal ; Interleukin-6 ; blood ; Lipid Peroxidation ; drug effects ; Lipids ; blood ; Male ; Plant Extracts ; therapeutic use ; Rats ; Rats, Wistar ; Salvia miltiorrhiza

To summarize the clinical experience and characteristics of Professor XU Xin in syndrome differentiation and treatment of polycystic ovary syndrome with insulin resistance （PCOS-IR）. XU Xin believes that the etiological factors of PCOS-IR is qi deficiency of the spleen and kidney， and the key disease mechanism is dysfunction in transportation and transformation of spleen and kidney， causing phlegm dampness and turbid heat accumulated in yangming， then evolving into the lower jiao， mixed with blood stasis， finally obstructing the chong （冲） and ren （任） mai and uterus. So in clinic， the method of boosting the kidney and fortifying the spleen was used through out the whole treatment commonly using modified Shoutai Pill （寿胎丸） and Sijunzi Decoction （四君子汤）. The main therapeutic method for treating PCOS-IR refers to clearing and draining dampness heat in yangming， invigorating blood and regulating period， with self-prescribed Yishen Quzhuo Formula （益肾祛浊方）， as a reference for the treatment of this disease.

AIM:To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic(AS)mice.METHODS:Eight-week-old SPF-grade male ApoE-/-mice and C57BL/6J mice used in this study.The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling.After AS establishment,the mice were exposed to chronic unpredictable mild stress(CUMS)for 6 weeks and then divided into five groups:control,CUMS,AS-regular diet(AS-r)+CUMS,AS-high-fat diet(AS-h),and AS-h+CUMS.During CUMS,open-field test and sucrose preference test were performed on mice in all groups.Blood lipids were characterized using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were performed to evaluate pathological changes in the aortic root.Cardiac function was assessed using echocardiography.The serum concentration of myocardial injury markers and ATP content was detected by ELISA.Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria.Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer.Western blot was conducted to quantify the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3.RESULTS:compared with the Control group,the total distance traveled,the number of entries into the central area,and the sucrose preference rate were significantly decreased in all CUMS groups(P<0.05).All AS groups exhibited varying levels of lipid deposition and endo-thelial damage in the aortic root,along with a significant reduction in cardiac function(P<0.05)and varying degrees of myocardial injury(P<0.05).In the AS-h+CUMS and AS-r+CUMS groups,myocardial mitochondrial structure was signifi-cantly disrupted.ATP content was significantly reduced(P<0.05),and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I,mitochondrial respiratory chain complexes I+II,and the maximum respiratory capacity of the electron transport system were all significantly decreased(P<0.05).Moreover,the protein levels of Bax and cleaved caspase-3 were significantly increased(P<0.05),while that of Bcl-2 protein was significantly decreased(P<0.05).CONCLUSION:Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice,promoting myocardial cell apoptosis and myocardial injury.

ObjectiveTo establish steroid-induced osteonecrosis of the femoral head （SANFH） cell model by using dexamethasone （DEX）-induced bone marrow mesenchymal stem cells （BMSCs） and demonstrate that Gushing Granules （GSNs） exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter （PI3K/Akt/Bad） signalling pathway. MethodsFirstly， SD rats were orally administered with drugs at a dose of 0.9 g·kg^-1 to prepare GSN-containing serum， and CCK-8 screening was used to determine the optimal dosage and duration of action. Then， BMSCs were cultured and treated with 1×10^-6 mol·L^-1 DEX， 10% GSN-containing serum， and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase （ALP） assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene （Bcl-2）， and Bcl-2-associated X protein （Bax）， osteocalcin （OCN）， and Collagen Ⅰ， we used Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%， and the duration of action is 48 hours. After modelling and grouping the cells in each group， the detection results showed that the SANFH model group had significantly lower cell viability， cell proliferation， and ALP expression， as well as protein and mRNA expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased （P<0.05，P<0.01）. After treatment with GSN-containing serum， cell viability， cell proliferation， and ALP expression， as well as expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ nucleic acids and proteins were significantly increased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased（P<0.05，P<0.01）. Compared with the GSN drug-containing serum group， the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically， the cell viability， cell proliferation， ALP expression， and the nucleic acid and protein levels of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ were all significantly decreased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased （P<0.05， P<0.01）. ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway， providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.