Purpose:The experimental study on the changes of HPV18 E6 gene,p53 mRNA and telomerase catalytic subunit (hTERT) mRNA in the process of HeLa cell apoptosis was carried out to supply a new way to diagnosing and treating cervical cancer. Methods:The apoptosis of HeLa cell was confirmed by means of electron microscope and flow cytometry. With PCR and RT PCR, we studied the changes and relations among HPV18 E6 DNA,p53 mRNA as well as hTERT mRNA in the process of HeLa cell apoptosis. Results:HPV18 E6 DNA and p53 mRNA had no changes but hTERT mRNA activation was inhibited by elemene emulsion. Conclusions:During apoptosis of HeLa cells induced by elemene emulsion, hTERT mRNA activation could apparently be inhibited. Hence, inhibition of telomerase activation may represent a new chemosensitisation for tumors resistant to anticancer drugs.

AIM:To investigate the role of mesenchymal stem cell-induced regulatory dendritic cells ( MSC-DCregs) in mouse acute graft-versus-host disease( aGVHD) model.METHODS: Bone marrow cells from BALB/c ( H-2 d ) mice were isolated and were induced to differentiate into DCs.The DCs were selected by flow cytometry, and after 10 d co-culture with MSCs, they were induced to be MSC-DCregs.Male 8-week-old C57BL/6 (H-2b) mice were used as do-nor mice.The female 8-week-old BALB/c (H-2d) mice, who had received 100 cm source-skin distance, 30 cm ×30 cm radiation field, 700 cGy total body irradiation (TBI) pretreatment were used as recipient mice.The recipients were divided into 5 groups:control group, TBI group ( injected with medium only) , bone marrow transplantation group ( injected with 1 ×107 bone marrow cells), aGVHD group (injected with 1 ×107 bone marrow cells and 1 ×107 spleen cells), and MSC-DCregs group (injected with 1 ×107 bone marrow cells, 1 ×107 spleen cells and 1 ×106 MSC-DCregs).The white blood cell count, recipients’ chimerism, clinical evaluation of aGVHD, survival analysis and pathological changes were deter-mined.RESULTS:Hematopoieic recovery was seen at 10 d after transplantation.The recipients’ chimerism was parallel to the donors’ at 30 d.The median survival time of the mice in aGVHD group and MSC-DCregs group was 27 d and 33 d, and the survival rates at 30 d were 20% and 100% (P<0.01), respectively.The clinical scores of the mice in MSC-DCregs group were lower than those in aGVHD group ( P<0.01) .Moreover, the pathological changes in the skin and liver of the mice in MSC-DCregs group were less serious than those in aGVHD group.CONCLUSION: The MSC-DCregs in-duce an aGVHD tolerance in vivo, and further research of its mechanism is still in great necessary.

Objective To study the effects of PVA-H coating thickness and tip angle on the tissue injury caused by the implantation of neural electrodes. Methods Simulated implantation experiments were conducted based on a tissue injury evaluation system to evaluate the tissue injury caused by electrode implantation. The coating thicknesses were controlled by the number of dip coating times (0, 1, 2, and 3), whereas the tip angles were set as 30°, 40°, and 50°. The maximum tissue strain and insertion force were selected as the measurement of the tissue injury. Results thicker hydrogel coating and larger tip angle would cause more serious tissue injury. Simultaneously, reducing the tip angle of the neural electrode could reduce the degree of the hydrogel coating effect on the tissue injury. When the tip angle was 30°, the maximum strain and the peak insertion force increased by 3.4% and 3.8%, respectively, whereas when the wedge angle was 60°, the maximum strain and maximum insertion force increased by 11.3% and 18.1%, respectively. Conclusions The hydrogel coating of the neural electrode increased the injury of biological tissues caused by the implantation of the neural electrode. However, the method of decreasing the tip angle of the electrode could reduce the degree of the negative effects of the hydrogel coating thickness on the implantation injury.

BACKGROUNDTo explore the feasibility of extended resection in selective patients with centrally located lung cancer.

METHODSFrom January, 1987 to December, 2001, lobectomy or pneumonectomy combined with extended resection of trachea, bronchus, heart or great vessels were carried out in 134 patients with centrally located lung cancer. The operations included bronchoplastic procedures in 80 cases, extended resection and reconstruction of left atrium and/or great vessels in 54 cases (32 cases with contemporary bronchoplasty).

RESULTSOperative death occurred in one case. Postoperative complications happened in 16 cases (11.9%). One hundred and seventeen cases (94.4%) were followed up. The 1-, 3-, 5-year survival rate was 84.7% (61/72), 56.7% (34/60) and 45.7% (21/46) respectively, while of those combined with tracheo bronchoplasty and/or cardiovascular reconstruction, the 1-, 3-, 5-year survival rate was 69.2% (36/52), 46.8% (22/47) and 22.2% (8/36) respectively. (P < 0.05), while expression of KAI1 mRNA did not relate to mutant P53 protein expression (P > 0.05).

CONCLUSIONSExtended resection combined with tracheo-bronchoplasty and/or cardiovascular reconstruction is feasible for selected patients with centrally located lung cancer and could improve the survival and life quality of patients.

Epilepsies are a group of chronic neurological disorders characterized by spontaneous recurrent seizures caused by abnormal synchronous firing of neurons and transient brain dysfunction. The underlying mechanisms are complex and not yet fully understood. Endoplasmic reticulum (ER) stress, as a condition of excessive accumulation of unfolded and/or misfolded proteins in the ER lumen, has been considered as a pathophysiological mechanism of epilepsy in recent years. ER stress can enhance the protein processing capacity of the ER to restore protein homeostasis through unfolded protein response, which may inhibit protein translation and promote misfolded protein degradation through the ubiquitin-proteasome system. However, persistent ER stress can also cause neuronal apoptosis and loss, which may aggravate the brain damage and epilepsy. This review has summarized the role of ER stress in the pathogenesis of genetic epilepsy.
Humans ; Endoplasmic Reticulum Stress/genetics* ; Unfolded Protein Response ; Endoplasmic Reticulum/pathology* ; Apoptosis ; Epilepsy/genetics*

Background and objective In recent years, Da Vinci robot system applied in the treatment of intratho-racic surgery mediastinal diseases become more mature. hTe aim of this study is to summarize the clinical data about mediasti-nal lesions of General Hospital of Shenyang Military Region in the past 4 years, then to analyze the treatment effect and prom-ising applications of da Vinci robot system in the surgical treatment of mediastinal lesions. Methods 203 cases of mediastinal lesions were collected from General Hospital of Shenyang Military Region between 2010 and 2013. hTese patients were di-vided into two groups da Vinci and video-assisted thoracoscopic surgery (VATS) according to the selection of the treatments. hTe time in surgery, intraoperative blood loss, postoperative drainage amount within three days atfer surgery, the period of bearing drainage tubes, hospital stays and hospitalization expense were then compared. Results All patients were successfully operated, the postoperative recovery is good and there is no perioperative death. hTe different of the time in surgery between two groups is Robots group 82 (20-320) min and thoracoscopic group 89 (35-360) min (P>0.05). hTe intraoperative blood loss between two groups is robot group 10 (1-100) mL and thoracoscopic group 50 (3-1,500) mL. hTe postoperative drainage amount within three days atfer surgery between two groups is robot group 215 (0-2,220) mL and thoracoscopic group 350 (50-1,810) mL. hTe period of bearing drainage tubes atfer surgery between two groups is robot group 3 (0-10) d and thora-coscopic group:5 (1-18) d. hTe difference of hospital stays between two groups is robot group 7 (2-15) d and thoracoscopic group 9 (2-50) d. hTe hospitalization expense between two groups is robot group (18,983.6±4,461.2) RMB and thoracoscopic group (9,351.9±2,076.3) RMB (All P<0.001). Conclusion hTe da Vinci robot system is safe and effcient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach, even though its expense is higher.

In order to characterize the immunogenicity and immunoprotection of the Staphylococcus aureus (S. aureus) surface protein Clumping factor A (ClfA), we amplified clfa genes from S. aureus Newman strain, Wood46 strain and HLJ23-1. The clfa gene from Newman strain was subsequently inserted into pQE-30 vector and the recombinant plasmid was transformed into Escherichia coli strain M15 (pREP4). The recombinant ClfA protein was expressed and purified. Then, we immunized mice with the purified recombinant protein. The antibody level and the concentration of cytokines were measured by enzyme-linked immunosorbent assay. Finally, immunized mice were challenged with S. aureus Newman, Wood46 and HLJ23-1. These results suggested that clfa gene sequences were highly conserved, and the recombinant ClfA was expressed correctly with good antigenicity. The antibody titer and the concentration of cytokines in the immunized groups increased significantly (P < 0.05) compared with control, and the mice in the immunized groups were protected against the challenge strains to some extent. These results showed that the ClfA had high immunogenicity and immunoprotective potential.
Animals ; Coagulase ; genetics ; immunology ; metabolism ; Escherichia coli ; genetics ; metabolism ; Immunization ; Mice ; Recombinant Proteins ; genetics ; immunology ; metabolism ; Staphylococcus aureus ; metabolism ; pathogenicity

The existing regulations and systems of the Swedish Medical Products Agency (MPA) have clear provisions on the definition, classification and listed on the market procecure of pharmaceutical products, and the supervision strictly follows the EU standards. Traditional Chinese Medicine (TCM) products belong to the category of Swedish Herbal Medicine Products (HMP) or Traditional Herbal Medicine Products (THMP) and are under the supervision of Swedish Pharmaceutical Products Administration (MPA). This paper analyzes the classification, relevant regulations and registration procecures of TCM products in Sweden. It is suggests that TCM enterprises should fully understand the EU regulations and guidance regulations before listed on the market of TCM products. They should also clarify the product category, and provide sufficient and accurate evidence. In the application process, they should pay attention to strengthening communication with the drug administration units of Sweden.

Background::It is controversial whether the apolipoprotein E epsilon 4 allele ( APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH). Methods::Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables. Results::Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [ k] = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers ( P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25], P < 0.001, k = 4, I2= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28], P < 0.001, k = 5, I2 = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23], P < 0.001, k= 8, I2= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20], P < 0.001, k= 10, I2= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14], P= 0.001, k= 6, I2= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16], P < 0.001, k = 8, I2 = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01], P = 0.04, k = 7, I2 = 0%). Conclusions::Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific. Meta analysis registration::PROSPERO, CRD 42021257775.

Background::Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.Methods::In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results::Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions::Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.