Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective To explore the potential category characteristics of self-management behavior in patients with lung cancer based on potential profile analysis,and to analyze the characteristic differences and influencing factors of self-management behavior in patients with different categories of lung cancer.Methods A total of 260 patients with lung cancer who had completed the main treatment program and were about to enter the follow-up period in a tertiary A general hospital in Zhejiang Province from July 2022 to May 2023 were selected by convenience sampling method as the investigation subjects.General Information Questionnaire,Lung Cancer Survivor Self-management Behavior Assessment Scale,Strategies Used by People to Promote Health,Hospital Anxiety and Depression Scale and Social Support Rating Scale were used for investigation.Potential profile analysis was used to explore the potential categories of self-management behavior in lung cancer patients and analyze its influencing factors.Results 252 patients were finally included.The results of potential profile analysis showed that lung cancer patients'self-management behavior could be divided into 3 potential categories,namely low self-management behavior-low emotion management group(11.90％),medium self-management behavior-low resource management group(45.24％),and high self-management behavior-low hope management group(42.86％).Logistic regression analysis showed that education level,previous surgery,tumor stage,anxiety level,depression level,self-efficacy level and social support level were the influencing factors of lung cancer patients'self-management behavior(P＜0.05).Conclusion The self-management behavior of lung cancer patients is at a moderate level,and there are obvious classification characteristics.It is suggested that medical staff should carry out personalized intervention measures according to the characteristics of self-management behavior of patients of various categories,so as to improve the level of self-management behavior of lung cancer survivors.

Humans ; Cytomegalovirus ; Cytomegalovirus Infections ; Antigens, Viral ; Immunity ; Autoimmune Diseases ; CD8-Positive T-Lymphocytes

OBJECTIVES: Accurate breast lesion surface localization can guarantee accurate biopsy and local treatment. But there is no guideline to regular equipment and methods for the localization of breast lesions. The conventional non-invasive localization method is marker-based localization. The advantages of this method are simple and efficient. The disadvantages are that markers disappear easily under coupling agents; the positioning length of markers cannot last long on skin; and healthcare associated infection due to many patients using the same marker pen is potentially unavoidable. Breast lesion sticker (called sticker for short) is a new-type localization medical instrument in 2020. Our study aims to explore the clinical value of a new lesion stickers in breast lesion surface localization via comparison of the sticker and marker pen localization methods. METHODS: This was a prospective cohort study. It was conducted in 67 patients who needed breast lesion surface localization before biopsy. The patients were randomly assigned into 2 groups. One group of patients used marker pen to mark breast lesion surface location by ultrasonography. The other group of patients used stickers. Patients labeled with markers on skin were swabbed agents before marking. Then the markers were checked by ultrasound scan. If the surface positions of breast lesion were not correct, the above procedure was repeated. In the sticker group, the stickers were released synchronously after the lesions were detected by ultrasound scan. Then locations were checked via scanning hole. If the surface positions of breast lesion were not correct, the above procedure was repeated. The accuracy of positioning, the length of positioning time and satisfaction of patients between the 2 groups were compared. The length of positioning time was calculated from the time when ultrasound detected the lesion to the time when the surface position of breast lesion was confirmed. The total score of patients' satisfaction was 5 points according to Service Quality Evaluation of SERVQUAL Scale, including sonographers' service attitude and their technical proficiency, other medical staffs' service attitude and their technical proficiency, hospital service procedures, positioning comfort, and positioning effects. RESULTS: All 67 patients were females, aged 18-66 (39.73±13.10). There were 35 patients in the marker pen group and 32 patients in the sticker group. The time length of group used marker pen to localization was 22-88 (52.20±2.90) s, and the sticker group was 3-15 (9.22±0.58) s in length. The length of positioning time for the stickers was significantly shorter than that of the marker (P<0.01). Both methods were accurate in the surface localization of lesions before operation. The total scores of patients' satisfaction was 4-5 (4.92±0.02) in the stickers group, and 1-5 (3.35±0.10) in the marker pen group. The patients' satisfaction scores with the sticker were significantly higher than those with the marker pen (P<0.01). The length of positioning time and patients' satisfication scores for sonographer with 20 years' working experience were shorter and higher than those of sonographer with 10 years' working experience, respectively (both P<0.05). CONCLUSIONS The new breast lesion positioning stickers have more advantages than the marker pen in localization efficiency. It could reduce the workload of medical workers and increase patients' satisfaction to some extent. The stickers can be used not only in the breast lesions surface localization, but also in the skin location of pleural effusion and ascites, the skin location of surface masses, the skin location of thyroid nodule, and many other clinical marker areas, to further expand the scope of clinical application and value of the stickers.
Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; Female ; Humans ; Male ; Prospective Studies ; Skin

OBJECTIVE：To study the efficacy and safety of sacubitril valsartan sodium tablets combined with Bailing capsules in the treatment of chronic left heart failure with renal insufficiency ，and to provide reference for clinical drug use. METHODS ： Totally 96 patients with chronic left heart failure with renal insufficiency who sought medical care in our hospital from Nov. 2018 to Nov. 2019 were divided into group A ，B and C according to table of random numbers ，with 32 cases in each group. Group A received conventional heart failure treatment and and Bailing capsules （2 g each time ，3 times a day ）；group B received conventional heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）；group C was given with heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）and Bailing capsules （2 g each time，3 times a day ）. 3 groups received consecutive 6 months of treatment. Clinical response rates of 3 groups were compared. Left heart function indexes [left ventricular end systolic diameter （LVESD），left ventricular end-diastolic diameter （LVEDD），left ventricular ejection fraction （LVEF）] and serological indexes [interleukin 1（IL-1），IL-6，N terminal brain natriuretic peptide precursor，glomerular filtration rate （GFR）] were detected before and after treatment. The occurrence of ADR were observed and recorded. RESULTS ：During this study ，a total of 6 patients fell off ，and eventually 90 patients completed the study ，including 29 cases in group A ，30 cases in group B and 31 cases in group C. Before treatment ，there was no statistical significance in left heart function indexes or serological indexes among 3 groups（P＞ 0.05）. After 6 months of treatment ，clinical response rate of group C was significantly higher than those of group A and B 163.com （P＜0.05）. Compared with before treatment ， LVEDD， LVESD and serological indexes of 3 groups were decreased significantly after treatment （P＜0.05），while LVEF and GFR were increased significantly （P＜0.05）；the changes of above indexes （except for IL- 1 level in serum ） in group C were significantly better than group A and B ，the changes of above indexes in group B （except for GFR ）were significantly better than group A （P＜0.05）. No significant ADR were observed in 3 groups. CONCLUSIONS ：Sacubitril valsartan sodium tablets combined with Bailing capsules can significantly decrease the level of serum inflammation factors ，and improve cardiac and renal function in patients with chronic left heart failure with renal insufficiency ，with good safety.

Objective:To investigate the effect of wild Cistanche deserticola crude polysaccharides (WCDCP) on the immune response of ovalbumin (OVA).Methods:42 ICR mice were randomly divided into the 9 g/L NaCl group (blank sample), WCDCP group (400 μg WCDCP), OVA group (10 μg OVA), low-dose WCDCP/OVA group (100 μg WCDCP+10 μg OVA), medium-dose WCDCP/OVA group (400 μg WCDCP+10 μg OVA), high-dose WCDCP/OVA group (800 μg WCDCP+10 μg OVA), and aluminum adjuvant/OVA group (positive concentration, 200 μg aluminum adjuvant+10 μg OVA). Each group included 6 mice. The mice were immunized by using two-point injection into the muscles of the hind legs of the mice. A total of 2 immunizations, and the immunization was boosted once every 2 weeks after the initial immunization. The body weight of the mice was weighed 7, 14, 21, and 28 days after the initial immunization of the mice, and the changes in body weight and growth status of the mice were observed. The IgG antibodies and antibody fractions were detected by indirect enzyme-linked immunosorbent assay. Twenty-one days after the initial immunization, the spleen lymphocyte proliferation level was detected by the thiazole blue method. Flow cytometry was used to detect the proportion of T cell subsets in the spleen and lymph nodes.Results:At 7 days after the initial immunization, the serum IgG antibody level (0.597 6±0.110 7) in the high-dose WCDCP/OVA group was significantly higher than (0.254 4±0.074 8) of the OVA group ( P<0.05). At 28 days after the initial immunization, the serum IgG, IgG1 and IgG2a antibody levels in the high-dose WCDCP/OVA group were higher than those in the OVA group, the comparison respectively were 0.972 3±0.243 8 vs. 0.389 2±0.077 4 ( P<0.05), 1.156 0±0.088 4 vs. 0.612 6±0.059 7 ( P<0.001), 1.648 0±0.103 9 vs. 0.557 2±0.181 5 ( P<0.001), and the differences were statistically significant. High-dose WCDCP can significantly promote the proliferation of spleen cells induced by concanavalin A ( P<0.001) and lipopolysaccharide ( P<0.05). High-dose WCDCP/OVA group can significantly stimulate the activation ratio of T cell subsets in the spleen. The proportion of CD3 +CD8 + T cells in the high-dose WCDCP/OVA group [(10.83±0.44)%] was significantly higher than that in the OVA group[(6.76±0.58)%] ( P<0.01), and the proportion of CD3 +CD4 + T cells [(28.17±1.67)%] was also significantly higher than that in the OVA group [(19.17±2.73)%] ( P<0.05). WCDCP had no effect on body weight (all P>0.05) and growth of mice. Conclusions:WCDCP can enhance humoral immune response and cellular immune response, and has no side effect on the growth of mice, suggesting that WCDCP can be used as a potential adjuvant for OVA.

Objective:To evaluate the performance of three antibody kits for novel coronavirus (SARS-CoV-2) and to investigate the feasibility and advantages of them in clinical application.Methods:A total of 104 patients who were admitted to Guangzhou Eighth People′s Hospital with COVID-19 from January to February 2020 were selected as research group. Fifty-one healthy subjects were selected during the same period as negative control group. Serum antibodies (IgM/IgG) against SARS-CoV-2 were detected using two kinds of colloidal gold kits (A and B kits) and one chemiluminescence kit (C kit). The positive rates of SARS-CoV-2 nucleic acid in different samples from patients with COVID-19 were retrospectively analyzed.Results:The clinical sensitivity of A kit to detect SARS-CoV-2-specific IgM and IgG was 77.88% (81/104) and 65.38% (68/104), respectively, and the clinical specificity was 70.59% (36/51) and 100.00% (51/51). However, the false positive rate in IgM detection was as high as 29.41% (15/51). The sensitivity of B kit to test total antibodies to SARS-CoV-2 was 63.46% (66/104), and the clinical specificity was 94.12% (48/51). The clinical sensitivity of C kit to detect SARS-CoV-2-specific IgM and IgG were respectively 31.73% (33/104) and 64.42% (67/104), and the clinical specificity were both 98.04% (50/51). There was a moderate correlation between the detection results of two colloidal gold kits and the chemiluminescence kit with the Kappa values of 0.462 and 0.587 ( Z=6.157, P<0.01; Z=7.345, P<0.01). C kit had the highest positive detection rate for IgG, and would be more reliable to be used for IgG detection in COVID-19 patients 14 d after onset. The total positive detection rate of nucleic acid in all types of samples was 63.46% (66/104). The highest positive detection rate was in throat swabs or sputum samples, followed by those in blood samples and anal swabs. No viral nucleic acid was detected in urine samples for the time being. Conclusions:SARS-CoV-2-specific antibodies could be detected in the early or late stage of COVID-19. The method of antibody detection has the advantages of shorter detection time, simple operation and high biological safety, indicating that it could be used as a supplementary or auxiliary detection for the diagnosis of suspected COVID-19 cases with negative nucleic acid test results. The chemiluminescence kit has good sensitivity and specificity, and is well recommended for clinical laboratories.

Objective: To explore the Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia (COVID-19) and their clinical values, and to provide theoretical basis for clinical diagnosis and treatment. Methods: A total of 164 patients, diagnosed with COVID-19 and admitted to Guangzhou Eighth People's Hospital from January to February 2020, were selected as the research group and divided into three groups (ordinary, severe, and critically severe pneumonia) according to the disease severity. Meandwhile 66 non-infected patients during the same period were selected as negative control group. The expressions of WBC, LYM, CRP, SAA, and PCT were retrospective studied and compared between groups. The diagnostic values of WBC, CRP, SAA and the combination of these three markers in all patients with COVID-19 and in different severity groups were analyzed by ROC curve. Results: Compared with control group (WBC count :8.13(6.51,9.42)×10⁹/L, LYM count:2.00(1.28,2.43)×10⁹/L), WBC count [4.94(4.05, 6.67) ×10⁹/L] and LYM count [1.33(0.94, 1.96) ×10⁹/L] of COVID-19 patients were significantly reduced (Z=-7.435, P<0.01; Z=-4.906, P<0.01) . Compared with the control group [CRP: 1.36 (0.57~5.67) mg/ml; SAA:[4.98 (4.80~15.75) mg/mL], CRP [7.93 (2.45~23.98) mg/ml] and SAA [34.13 (4.83~198.40) mg/ml] were increased in research group (Z=-5.72, P<0.01; Z=-4.166, P<0.01) . PCT in the control group and the research group were 0.100 0(0.030 6~0.100 0)ng/ml and 0.044 5(0.031 6~0.077 0)ng/ml, respectively. There was no statistical difference between two groups (Z=-1.451, P=0.147) . The areas under the ROC curve (AUC) of WBC, CRP and SAA in patients with COVID-19 were 0.814, 0.742, 0.673, respectively (P<0.01), while the AUC of the combination of three indexes for COVID-19 diagnosis was 0.882, with 83.33%(55/66) specificity and 84.76% (139/164) sensitivity, P<0.01.The AUCs of WBC, CRP, and SAA for predicting severe and critically severe COVID-19 were 0.799, 0.779, and 0.886 , respectively (P<0.01), and the AUC of the combination of three indexes for the diagnosis of severe and critically severe COVID-19 was 0.924, with 78.67% (118/150) specificity and 14/14 sensitivity (P<0.01). Conclusion Combining detection of WBC, CRP and SAA can improve the specificity and sensitivity of COVID-19 diagnosis, with a high diagnostic value for severe and critically severe COVID-19.

OBJECTIVETo study the expression and clinical significance of MTDH and VEGF in triple-negative breast cancer (TNBC).

METHODSTissue samples of 168 breast cancers (including 112 TNBC tissue and 56 non-TNBC tissue), 10 breast fibroadenomas and 15 normal breast tissues were collected. Postoperative specimens were examined by immunohistochemistry for MTDH and VEGF expression. The correlation between the expression of MTDH and VEGF and clinicopathological features was analyzed.

RESULTSMTDH and VEGF were expressed in 57.1% and 49.4% of breast cancer patients, 64.3% and 56.3% in TNBC patients, respectively, significantly higher than that in the non-TNBC tissues, breast fibroadenomas and normal breast tissues (P<0.05 for all). Statistically significant correlation was found between the MTDH and VEGF expressions (r=0.356, P<0.001). Moreover, MTDH expression was correlated with tumor size, BMI index, lymph node metastasis, pathological stage, recurrence and metastasis, and the expression of p53 and Ki-67 proteins (P<0.05 for all). The VEGF protein expression was correlated with lymph node metastasis, pathological staging, recurrence and metastasis, and the expression of Ki-67 protein (P<0.05 for all). The patients with high expression of MTDH and VEGF showed a lower DFS and OS (P<0.05 for both).

CONCLUSIONSMTDH and VEGF expression may be correlated with tumor angiogenesis and progression and has the potential to be valuable prognostic factors in patients with TNBC.

Biomarkers, Tumor ; metabolism ; Breast ; metabolism ; Cell Adhesion Molecules ; metabolism ; Disease-Free Survival ; Female ; Fibroadenoma ; blood supply ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Neovascularization, Pathologic ; Prognosis ; Triple Negative Breast Neoplasms ; blood supply ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

Objective To explore the potential mechanisms of non-small cell lung carcinoma cells to rsTRAIL protein-induced apoptosis by phosphatidylinositol 3′-kinase (PI3K/Akt)inhibitor LY294002,and to provide new ways to increase killing activities of rsTRAIL protein for non-small cell lung cancer.Methods The A549 cells at logarithmic growth phase were selected and randomly divided into rsTRAIL group and LY294002+rsTRAIL group. The inhibitory rate of growth of the A549 cells was tested by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry analysis. The expression levels of Ser473 phosphorylated form of Akt (p-Akt),c-FLIPL protein and Bcl-2 protein in the A549 cells in two groups were analyzed by Western blotting method. Results The inhibitory rate of growth of the A549 cells in LY294002+rsTRAIL group (74.6 %± 2.63%)was higher than that in rsTRAIL group (5.61% ± 0.32%) (P< 0.05 ). Compared with rsTRAIL group, the percentage of the cells at G0/G1 phase in LY294002+rsTRAIL group was increased(P<0.05)and the percentage of the cells at S phase was decreased(P<0.05).The apoptotic rate of the A549 cells in LY294002+rsTRAIL group (61.5%±3.02%)was higher than that in rsTRAIL group (3.21%±0.96%)(P<0.05). The Western blotting results showed that the expression levels of p-Akt, c-FLIPL and Bcl-2 proteins in the A549 cells in LY294002+rsTRAIL group were decreased (P<0.05 )and the ratio of Bax/Bcl-2 was increased (P<0.05 ) compared with rsTRAIL group.Conclusion LY294002 can increase the killing activity of rsTRAIL protein in A549 cells by inhibiting the activity of PI3K.