The cGAS-STING pathway plays a significant role in host defense against viral and bacterial infection.In the process,the cytoplasmic free DNA,considered as a danger signal,is recognized by nucleotidyl transferase cGAS.cGAS is activated by double-stranded DNA (dsDNA) and catalyzes the synthesis of a noncanonical cyclic dinucleotide 2'5'-cGAMP from adenosine triphosphate (ATP) and guanosine triphosphate (GTP).cGAMP serve as an endogenous second messenger to stimulate the induction of type Ⅰ interferons via STING.In addition to the exogenous bacterial or viral DNA,abnormal deposition of host DNA in cytosol also activates the cGAS-STING signaling pathway cascade,resulting in inflammation and autoimmune diseases.Subsequent studies found that this pathway also plays an important role in tumor's responsiveness to radio-therapy and chemo-therapy.Activation of cGAS-STING pathway produces or enhances the therapeutic efficacy.These findings suggest that specifically interfering with cGAS-STING activation may hold therapeutic value for the treatment of cancer,infection and inflammatory diseases.In this paper,the activation mechanism of cGAS-STING pathway and its relationship with the treatment of diseases were summarized,and the regulation of cGAS-STING pathway was introduced in detail.

Objective To observe ultrastructural changes in a clinical isolate of Penicillium marneffei(PM) before and after treatment with amphotericin B or voriconazole by using scanning electron microscopy (SEM)and transmission electron microscopy (TEM). Methods A microdilution method was performed to determine the minimum inhibitory concentration (MIC)of amphotericin B and voriconazole against a clinical isolate of PM. Then, the PM isolate was treated with amphotericin B or voriconazole at their MICs and 10-fold MICs for 24, 48 and 72 hours. The ultrastructural changes in this isolate before and after the treatment were observed by using SEM and TEM. Results After the treatment with amphotericin B, SEM showed that the conidia or yeast cells of the PM isolate were gradually damaged, and their outer layers experienced detachment, shrinkage, breakage and adhesion with the increase in treatment duration and concentrations of amphotericin B; TEM also showed degenerated mitochondria, broken nuclei and cell walls, and shrunken cytoplasmic membrane with disappearance of cytoplasmic organelles. Similarly, the damage, shrinkage, shriveling and collapse of PM cells were seen by using SEM, and TEM showed many high-density electron-dense granules in cytoplasm, degeneration of mitochondria, roughening of cell wall surface, damage and shrinkage of cytoplasmic membrane, and disappearance of cytoplasmic organelles after voriconazole treatment. Conclusions Amphotericin B and voriconazole both had a strong antifungal effect on PM, and could induce evident ultrastructural changes, which were positively associated with treatment duration and concentrations. Moreover, amphotericin B caused more severe damage to PM compared with voriconazole.

Objective:To investigate the ultrasonographic characteristics and risk factors of breast cancer internal mammary lymph node (IMLN) metastasis.Methods:A retrospective analysis of 296 first diagnosed breast cancer patients in the Fourth Hospital of Hebei Medical University from March 2010 to May 2020. IMLN was divided into metastatic group (236 cases) and non-metastatic group (60 cases) based on pathology. Chi-square test and independent sample t test were used to analyze the ultrasound characteristics of IMLN metastasis and factors related to metastasis. ROC curve analysis of IMLNs were plotted to obtain the diagnostic thresholds and their sensitivity and specificity.Univariate and multivariate Logistic analysis was used to analyze the risk factors of IMLN metastasis. Results:①The appearances of IMLN in ultrasound were normal type, thickened-cortex type, unclear hilus structure type and thickened-nodular soft tissue type. ②In the two groups, the differences in IMLN long diameter, thickness diameter, number, and lymphatic hilum structure type were statistically significant (all P<0.05), and there were no significant differences in IMLN long diameter/thickness diameter and IMLN blood supply (all P>0.05). ③The long diameter threshold of IMLN for diagnosis of metastasis was 10.5 mm, the are under the ROC curve(AUC) was 0.825, with sensitivity of 58.5% and specificity 93.3%; thickness and diameter threshold was 4.5 mm, AUC was 0.790, with sensitivity 66.9% and specificity 75.0%. The sensitivity and specificity of the diagnosis of long-diameter combined structure type were 56.3% and 93.3%, respectively; the sensitivity and specificity of the diagnosis of thick-diameter combined structure type were 64.8% and 81.7%, respectively. The cortical thickness threshold was 1.9 mm, and the diagnostic sensitivity and specificity were 91.9% and 86.7%, respectively. ④The risk factors of IMLN metastasis inculded univariate analysis showed tumor length, tumor volume, axillary lymph node long diameter, axillary lymph node metastasis, and clavicle lymph node metastasis. There was a statistically significant difference in the pathology of the lower lymph nodes between the two groups ( P<0.05). Multivariate analysis showed that the long diameter of the tumor and the metastasis of the axillary lymph nodes were independent risk factors of IMLN metastasis. Conclusions:The metastatic IMLN mostly manifest as no lymphatic hilum structure or cortical thickening (≥1.9 mm), and multiple IMLN can help diagnose metastasis.Ultrasound can better assess breast cancer IMLN metastasis, and the diagnostic efficiency of IMLN long-diameter combines structure type is higher.Independent risk factors for IMLN metastasis include tumor size and axillary lymph node metastasis.

Objective To explore the change of cerebral microcirculation before and after clipping of intracranial aneurysm using CT perfusion (CTP)imaging.Methods CTP images of 70 patients diagnosed intracranial aneurysm by CTA were retrospectively an-alysed.They were divided into four groups according to have or not intracranial arterial spasm:A group:Preoperative CVS,postop-erative CVS (4 cases),B group:Preoperative CVS,postoperative nCVS (13 cases),C group:Preoperative nCVS,postoperative CVS (20 cases),D group:Preoperative nCVS,postoperative nCVS (33 cases).CBV/CBF/MTT were measured in four groups be-fore and after surgery,and analyzed statistically.Results (1)The postoperative CBV/CBF/MTT was compared with the preopera-tive data.There were statistically significant in CBVA/B/C/D/CBFA/B/D/MTTA/B during the surgery (P <0.05 ).There were no statistically significant in the CBFC and MTTC/D during the surgery (P >0.05).(2)There were statistically significant in the△CBVBC/BD/△CBFAB/BC/BD/△MTTAB/BD (P < 0.05 ).△CBVAB/AC/AD/CD/△CBFAC/AD/CD/△MTTAC/AD/BC/CD were no statistically significant (P >0.05).Conclusion CTP can early and accurately predict the change of cerebral microcircu-lation after surgery.

Objective To explore whether CD44 +/CD24 + expressing cervical cancer cells are resistant to X-ray irradiation and investigate the underlying mechanism.Methods Cervical cancer cell line (Siha) was cultured in vitro and the CD44 +/CD24 + expressing cells were sorted with a flow cytometer.The cells were irradiated with 8,16 and 30 Gy of 6 MV X-rays.Colony formation test was used to evaluate the radiosensitivity of CD44 +/CD24 + expressing cervical cancer cells.Cell morphology was observed by electronmicroscopy,cell apoptosis was analyzed with a flow cytometer and also verified with a DNA ladder assay.Gene expression was determined by RT-PCR.Results After radiation,the ratio of CD44 +/CD24 + cells significantly increased.Compared to Siha cells,the radiosensitivity of CD44 +/ CD24 + cells decreased (t =93.99-400.45,P ＜0.05),and the expressions of bcl-2,survivin and Oct4 mRNA increased in CD44 +/CD24 + cells (t =221.35,941.65,82.27,P ＜0.01).Both apoptotic body and specific DNA ladder pattern were observed in cells but not in the CD44 +/CD24 + Sihacells which had no obvious morphological changes of apoptosis.Conclusions The CD44 +/CD24 + expressing cervical cancer cells are resistant to X-rays due to expression of anti-apoptosis factors.

Objective To develop and validate the Knowledge-Attitude-Practice Scale for Prevention of Occupational Low Back Pain for Nurses (hereinafter referred to as KAP). Methods Based on the knowledge, attitudes and practice theory, a list of 48 potential items were developed by reviewing literatures related to the prevention of occupational low back pain in nurses. The Delphi expert consultation method was used to conduct two rounds of consultation on the items, and the KAP (draft) with 31 items was formed. A total of 269 nurses in a hospital in Guangdong Province were selected as study subjects by convenience sampling method and investigated with the KAP (draft). The list was selected and its validity tested using SPSS 25.0 software. Results The authority degrees of two rounds of expert consultation were 0.919 and 0.922. All of the recovery rates of valid questionnaires were >80.0%, with the coefficients of variation ranged from 0.07 to 0.40 and 0.05 to 0.28. The Kendall's concordance coefficients were 0.198 and 0.274, respectively (all P<0.05). After item selection, five items were removed, resulting in the KAP with 28-item including three dimensions： knowledge, attitude and behavior. The scale-level content validity index/average was 0.976, and the item-level content validity index ranged from 0.833 to 1.000, as assessed by experts. The scale demonstrated 100.0% for convergent and discriminative validity of the three dimensions. The exploratory factor analysis revealed three factors with a cumulative variance contribution rate of 51.0%. Cronbach's alpha coefficients for the overall scale and knowledge, attitude, and behavior dimensions were 0.880, 0.878, 0.895, and 0.877, respectively. Split-half reliability coefficients were 0.922, 0.863, 0.852, and 0.820, respectively. Conclusion The KAP shows good reliability and validity and can be used to assess knowledge, attitude and practice levels related to occupational low back pain prevention among nurses.

To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.

Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

Objective To investigate the role of chemokine ligand 19 (CCL19) and protein kinase-B (AKT) signaling pathway in lung cancer development. Methods The human lung adenocarcinoma cell line, A549 cells, in logarithmic growth phase were randomly divided into five groups： blank control group, solvent control group, CCL19 treatment group, AKT inhibition group, and antibody neutralization group. The blank control group received no treatment. The other four groups were treated with dimethyl sulfoxide, CCL19, MK-2206 (AKT inhibitor), and a combination of CCL19 and MK-2206, respectively. Cell viability was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated using the cell scratch and transwell assays. The relative expression levels of Pan-AKT, p-AKT (Ser473), p-AKT (Thr308), E-cadherin (E-cad), N-cadherin (N-cad), and Snail proteins in A549 cells were detected using Western blotting. Lung cancer tissue samples from 60 patients with non-small cell lung cancer (NSCLC) were collected, and the expression of CCL19 and matrix metalloproteinase 9 (MMP9) proteins in the specimens was examined using immunohistochemistry. Results The survival rate of A549 cells in the AKT inhibition group and antibody neutralization group was lower than that in blank control group, solvent control group, and CCL19 treatment group (all P<0.05). The cell scratch assay result showed that the cell migration rate of the CCL19 treatment group was higher at 36.0 and 48.0 hours than those of the blank control group, solvent control group, AKT inhibition group, and neutralizing antibody group (all P<0.05). The Transwell assay result showed that the invasion amount of A549 cells in the AKT inhibition group was less than that in the CCL19 treatment group (P<0.05). Compared with the blank control group, the relative expression of E-cad protein in the CCL19 treatment group decreased, while the relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad and Snail proteins increased (all P<0.05). The relative expression of p-AKT (Ser473), p-AKT (Thr308), N-cad, and Snail proteins in A549 cells decreased (all P<0.05), and relative expression of E-cad protein increased (all P<0.05) in the AKT inhibition group and antibody neutralization group compared with the blank control group, solvent control group, and CCL19 treatment group. There was no significant difference in the expression of CCL19 and MMP9 in lung cancer tissues of NSCLC patients in Xuanwei City, Gejiu City, and other regions (all P>0.05). The expression of CCL19 and MMP9 in NSCLC patients with lymph node metastasis was higher than in patients without lymph node metastasis (all P<0.01). Conclusion CCL19 can promote the invasion and metastasis of lung cancer cells and induce epithelial-mesenchymal transition. Its expression level is related to lymph node metastasis in NSCLC patients. The AKT signaling pathway may be an important mechanism underlying lung cancer development.

Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.