BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

With the increasing number of cancer patients, the aging population, the shortage of medical resources and other problems in China, the demand for palliative care is gradually increasing. However, nursing staff are the main implementors of palliative care, and their cognitive level of palliative care is closely related to the quality of palliative care service and the outcome of patients. By summarizing assessment tools of palliative care knowledge, attitudes and skills, this review aims to provide a reference for developing appropriate palliative care assessment tools for nursing staff in China.

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*

Objective:To investigate the efficacy and safety of cedilanid in the treatment of severe pneumonia in infants and the value of preventing heart failure.Methods:A total of 80 children with severe pneumonia admitted to Dezhou Maternal and Child Health Hospital from January 2019 to December 2020 were selected and randomly divided into the control group and the observation group, with 40 cases in each group. The control group received comprehensive treatment, while the observation group was treated with cedilanid (0.01 mg/kg, one-time intravenous injection) on the basis of the control group. The efficacy of both groups was observed after 5 d of treatment. The incidence of heart failure, correction time of heart failure, improvement time of symptoms and signs, and length of hospitalization time were compared between the two groups; the inflammatory markers, myocardial markers and arterial blood gas indexes were compared between the two groups before and after the treatment.Results:The total effective rate in the observation group was higher than that in the control group, and the incidence of heart failure in the observation group was lower than that in the control group: 90.0% (36/40) vs. 72.5% (29/40), 32.5%(13/40) vs. 10.0%(4/40), the differences were statistically significant ( χ2 = 4.02, 4.10, P<0.05). The improvement time of symptoms and signs (restlessness elimination, respiratory improvement, heart rate improvement and disappearance of rhonchus in lung) in the observation group were less than those in the control group ( P<0.05). The levels of procalcitonin (PCT) and N-terminal pro-brain natriuretic peptide (NT-ProBNP), myocardial troponin I(cTnI), and creatine kinase isoenzyme (CK-MB) in the observation group after treatment were lower than those in the control group: (6.15 ± 1.03) μg/L vs. (10.85 ± 2.12) μg/L, (112.02 ± 30.09) ng/L vs. (215.39 ± 55.08) ng/L, (0.68 ± 0.17) μg/L vs. (1.12 ± 0.34) μg/L, (19.05 ± 6.11) U/L vs. (28.97 ± 7.82) U/L, P<0.05. The levels of oxygen partial pressure (PaO 2), blood oxygen saturation (SaO 2) and oxygenation index (PaO 2/FiO 2) in the observation group after treatment were higher than those in the control group: (6.15 ± 1.03) μg/L vs. (10.85 ± 2.12) μg/L, (112.02 ± 30.09) ng/L vs. (215.39 ± 55.08) ng/L, (0.68 ± 0.17) μg/L vs. (1.12 ± 0.34) μg/L, (19.05 ± 6.11) U/L vs. (28.97 ± 7.82) U/L, P<0.05. Conclusions:Early application of small dose of cedilanid in infants with severe pneumonia can effectively reduce the occurrence of heart failure, improve the clinical symptoms and blood gas indicators, with significant curative effect, which is worthy of promotion.

Background::Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.Methods::Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.Results::We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP +-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. Conclusion::This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.

Objective To establish a clinical cytokine test method based on flow multiple microarray technology,and discuss its clinical significance by observing the change of cytokines level in the early stage of influenza.Methods 54 cases of influenza A virus positive and 20 cases of influenza A virus negative influenza like patients were selected as influenza group.Among them,influenza A virus positive patients were divided into mild group and severe group,influenza A virus negative influenza like patients were as neg-ative group.In addition,35 healthy people were selected as the control group,and the cytokine of all the whole blood samples was detected and statistically analyzed.Results Interleukin-6(IL-6),interleukin-21(IL-21),interleukin-12p70(IL-12p70),interleukin-1 β(IL-1 β)and interleukin-10(IL-10),chemokine-10(IP-10),interleukin-2(IL-2),monocyte chemoattractant protein-1(MCP-1)lev-els were significantly higher in the patients with early onset of influenza,and the difference was statistically significant(P<0.05). The difference of interferon-γ(IFN-γ)between the influenza group and the control group was not statistically significant(P> 0. 05).The levels of IL-6 and IP-10 in the severe group were higher than that of the mild group and the negative group,and the differ-ence was statistically significant(P<0.05).Conclusion IL-6,IL-21,IL-12p70,IL-1 beta,IL-10,IP-10,IL-2 and MCP-1 levels can be used as clinical biological evaluation indicators of patients with fever,of which IL-6 and IP-10 can be used as important indicators for disease progression assessment.

Objective To observe the effects of dredging collaterals and activating blood worm Chinese materia medica on angiogenesis related factors of lung cancer in hypoxic environment. Methods The lung cancer A549 cells were cultured in vitro to simulate tumor hypoxia microenvironment by the hypoxia workstation, and different concentrations of Scorpio, Scolopendra and Gecko medicated serum were added. MTT method was used to detect cell proliferation and screen the best medicine concentration and duration of action. Lung cancer A549 cells were administrated by the three kinds of medicated serum, and cells were collected and supernatant was cultured. Contents of VEGF, TGF-β1, and bFGF were detected by ELISA. Results Three kinds of medicated serum had the inhibitory effect on both added normoxia and hypoxia in cultured A549 lung cancer cells. 7.5% concentration of medicated serum was selected, and 24 h later were used in later experiments. Scorpio, Scolopendra and Gecko medicated serum can more reduce the contents of VEGF, TGF-β1 and bFGF in the supernatant of A549 cell compared with the control group (P<0.05, P<0.01). Conclusion Dredging collaterals and activating blood worm Chinese materia medica had inhibitory effect on cancer cells and the regulation of angiogenesis related cytokines in the condition of normoxia and hypoxia.

OBJECTIVE:To provide reference for perioperative rational prophylactic application of antibacterials in type Ⅰ in-cision operation. METHODS:4 201 patients underwent type Ⅰ incision operation were collected from a class A grade three hospi-tal during Mar. 2013-Feb. 2015. The perioperative prophylactic application of antibacterials in type Ⅰ incision operation were ana-lyzed statistically. RESULTS:Of 4 201 patients underwent type Ⅰ incision operation,there were 2 399 cases of prophylactic appli-cation of antibiotics(accounting for 57.10%). Cephalosporins andβ-lactam/β-lactamase inhibitor were the main classes of antibacte-rials for preventive use,accounting for 45.60%and 19.76%,respectively. The frequency of using cefazolin,ceftriaxone and amoxi-cillin-clavulanic acid ranked the top 3 places, among which there was 823 cases of unsuitable prophylactic medication time (34.31%),and 855 cases of prophylactic medication time >48 h(accounting for 35.64%). CONCLUSIONS:There still is unrea-sonable perioperative prophylactic application of antibacterials in type Ⅰ incision operation in this hospital. It is necessary to strengthen the supervision of antibacterials and conduct regular rational antibacterials use seminars in order to promote rational use of antibacterials.

Objective To discuss the relationship between hepatitis B virus (HBV) genotype and HBV DNA ,liver fibrosis ,liver function and HBeAg .Methods HBV genotypes ,HBV DNA ,liver fibrosis indicators and alanine aminotransferase(ALT ) ,aspartate aminotransferase(AST ) ,total bilirubin(TBIL) ,albumin(ALB) and HBV e antigen(HBeAg) were detected in patients with serum hepatitis .All data were statistically analyzed .Results There was no significant difference of HBV DNA ,ALT ,AST ,TBIL ,ALB , procollagen- Ⅲ -peptide ,type Ⅳ collagen ,hyaluronic acid and laminin between patients with B and C genotype infection (P> 0 .05) . However ,HBeAg level in patients with C genotype infection was higher than that in patients with B genotype infection (P< 0 .05) . Conclusion There might be no significant difference of HBV DNA ,liver function and liver fibrosis between patients with B and C genotype infection ,but HBeAg level in patients with C genotype infection could be higher than patients with B genotype infection .