Application of B-ultrasound for localization and its impact on first-attempt success rates of nasogastric tube insertion in critically ill patients.

The objective of this study is to explore the application effect of B-ultrasound positioning in assisting nasointestinal tube implantation in critically ill patients. This study is a retrospective study. In this study, 90 cases of severe patients with nasointestinal tube implantation were included. According to the different ways of nasointestinal tube insertion received by patients, 61 patients with conventional blind insertion methods were included in the blind insertion group, and 29 patients with conventional methods and B-ultrasound assisted positioning were included in the B-ultrasound positioning group. The general clinical data, success rate of catheterization, catheterization time, pyloric passage rate, and target nutritional value time of the 2 groups were compared. The changes of the 2 groups after catheterization were compared by SOFA and APACHE II. The contents of albumin and lymphocyte count were compared between the 2 groups before and after catheterization. The time of target nutritional value of the patients of the B-ultrasound positioning group was markedly decreased comparing with the patients of the blind insertion group. The index of catheterization time of the patients between the blind insertion group and B-ultrasound positioning group had no obvious contrast. The APACHE II score and SOFA score of the patients of the B-ultrasound positioning group were obviously lower than the blind insertion group. The contents of lymphocyte count of the patients of the B-ultrasound positioning group were markedly increased comparing with the patients of the blind insertion group after catheterization, but the contents of albumin content had no obvious change. The scores of respiratory system, circulatory system, nervous system, and urinary system in the B-ultrasound positioning group were significantly higher than those in the blind insertion group, while the COPT scores were significantly lower than those in the blind insertion group. B-ultrasound assisted nasointestinal tube implantation is well tolerated in critically ill patients, and can effectively ameliorate the nutritional status and of the ill patients.

Wee1 epigenetically modulates H2B mono-ubiquitination at K120 lysine and DNA double-strand break repair through phosphorylation of H2BY37-dependent manner in small-cell lung cancer.

BACKGROUND: DNA damage repair is a crucial mechanism highly related to therapy resistance for various therapeutic strategies. Our previous results have shown that the degree of drug resistance in small-cell lung cancer (SCLC) cell lines was proportional to both the transcription and expression levels of Wee1, indicating that Wee1, an evolutionarily highly conserved kinase, plays a vital role in the therapeutic resistance of SCLC. In the present study, we aim to determine the nonclassical mechanism of Wee1 on DNA repair regulation. METHODS: Western blot was conducted to determine the mono-ubiquitination level of H2Bub. Comet assay was used to evaluate the degree of DNA damage. Immunofluorescence was conducted to determine the DNA repair markers. Co-immunoprecipitation was utilized to assess the potential interactions with H2BY37ph. MTT assays were used to evaluate the survival rates of SCLC cells. RESULTS: Overexpression of Wee1 increases the level of H2BK120ub and alleviates ionizing radiation (IR)-induced DNA damage in SCLC cells. Moreover, H2BK120ub is a crucial molecule in Wee1-mediated double-strain break (DSB) repair in SCLC cells. Mechanisms study indicated that H2BY37ph is involved in Wee1-mediated H2BK120ub through interaction with the E3 ubiquitin ligase RNF20-RNF40 complex and upregulates its phosphorylation, mutation of H2BY37 phosphorylation sites attenuated DSB repair and enhanced the sensitivity of IR-induced SCLC cell death. CONCLUSION: H2BY37ph produces crosstalk with H2BK120ub in an E3 ubiquitin ligase-dependent manner, promoting Wee1-mediated DSB repair in SCLC cells. This study clarifies the nonclassical mechanism of Wee1 regulation of DSB repair, which provides a theoretical basis for the clinical understanding of the regulatory network of Wee1 and its use as a target for overcoming multiple types of therapeutic resistance.

MiR-623 links lncRNA RP11-89 and cyclin D1 to regulate the proliferation of glioblastoma cells.

PURPOSE: The tumorigenesis of bladder cancer has been proven to be related to the increased expression of lncRNA RP11-89, the participation of which in glioblastoma (GBM) is unknown. We predicted that RP11-89 could be targeted by miR-623, which targets cyclin D1. We then analyzed the role of RP11-89 in GBM. MATERIALS AND METHODS: Samples of both GBM and paired non-tumor tissue were obtained from 58 GBM patients to analyze the expression of RP11-89 and miR-623 through RT-qPCR. The direct binding of miR-623 to RP11-89 was analyzed with RNA-RNA pull down. The role of RP11-89 and miR-623 in regulating each other's expression was analyzed with overexpression assay. The role of RP11-89 and miR-623 in regulating the expression of cyclin D1 and GBM cell proliferation was analyzed by Western blot and BrdU assay, respectively. RESULTS: RP11-89 was expressed in high amounts in GBM, while miR-623 was expressed in low amounts in GBM. RP11-89 and miR-623 were not closely correlated, while miR-623 directly bound to RP11-89. RP11-89 and miR-623 showed no direct role in each other's expression. RP11-89 suppressed the role of miR-623 in downregulating cyclin D1 and GBM cell proliferation. CONCLUSIONS: Therefore, miR-623 may link lncRNA RP11-89 and cyclin D1 to regulate the proliferation of GBM cells.

Body mass index change in relation to longitudinal systolic blood pressure: An age- and sex-matched and repeated measures study.

BACKGROUND AND AIMS: The positive association between mean systolic blood pressure (SBP) and body mass index (BMI) diminished or reversed over the past four decades. The primary aim of this study was to evaluate effects of BMI change on longitudinal SBP. METHODS AND RESULTS: A total of 3638 participants who had annual health examination from 2015 to 2019 were included and matched by age and sex according to BMI levels. BMI and SBP were measured annually and their association were assessed by a linear mixed-effects regression model. The normal weight participants had a sustained weight gain as well as SBP increase during the study period (all Ptrend <0.001). The obese participants had a sustained weight loss but SBP did not decrease simultaneously. If BMI change was considered, the obese participants with BMI loss had a significant decrease of SBP during the study period (Ptrend = 0.0012). Mixed-effects models showed that weight gain was more influential on longitudinal SBP in the normal weight participants and weight loss was in the obese participants. The obese group with BMI loss had a decrease of SBP by 5.01 mmHg (95% confidence interval: 2.56 mmHg, 7.46 mmHg) compared to their counterparts with BMI maintenance from 2015 to 2019. CONCLUSIONS: The effect of weight change on longitudinal SBP was varied among BMI groups. With the increase of baseline BMI level, the positive effect of weight loss on SBP became greater and the negative effect of weight gain on SBP were attenuated.

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice.

PURPOSE: Sodium-glucose transporters (SGLTs) are important targets for therapeutic intervention of type 2 diabetes. This study aims to evaluate the physiological influences of diabetes mellitus and the potential impacts of metformin and fluoxetine on SGLTs expressions. METHODS: Alterations of SGLT1 and SGLT2 were measured in organs involved in glucose homeostasis (kidney, intestine, liver and pancreas) of streptozotocin (STZ) and high-fat diet (HFD) induced diabetic mice by western blotting and real-time PCR (RT-PCR) respectively. RESULTS: In kidney, duodenal segments of intestine, liver, and pancreas of HFD diabetic mice, expressions of SGLT2 were all elevated compared to control mice. The level of SGLT1 was significantly increased in intestine, but was decreased in pancreas. SGLT1 expression in kidney was unaffected, and SGLT1 was undetectable in hepatocytes. Similar results were obtained in STZ diabetic mice. More importantly, here we noticed metformin decreased levels of SGLT2 in kidney, intestine, and pancreas of HFD mice markedly. Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well. In contrast, fluoxetine increased abundances of SGLT2 and SGLT1 in kidney of HFD mice, but decreased SGLT1 expression in intestine. CONCLUSIONS: The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.

Puerarin ameliorates hyperglycemia in HFD diabetic mice by promoting ß-cell neogenesis via GLP-1R signaling activation.

BACKGROUND: Diabetes is characterized by ß-cell loss and dysfunction. A strategy for diabetes treatment is to promote new ß-cell formation. Puerarin is an isoflavone from the root of Pueraria lobata (Willd.) Ohwi. Our previous study demonstrated puerarin could ameliorate hyperglycemia in diabetic mice. However, related mechanisms and potential roles of puerarin in ß-cell neogenesis have not been elucidated. PURPOSE: The present study aims to investigate whether anti-diabetic effect of puerarin is dependent on promoting ß-cell neogenesis via GLP-1R signaling activation. METHODS: A high-fat diet (HFD) induced diabetic mouse model was applied to investigate effects of puerarin in vivo, exendin-4 (GLP-1R agonist) and metformin were used as positive controls. Moreover, related mechanisms and GLP-1R downstream signal transduction were explored in isolated cultured mouse pancreatic ductal cells. RESULTS: Puerarin improved glucose homeostasis in HFD diabetic mice significantly. Markers of new ß-cell formation (insulin, PDX1 and Ngn3) were observed in pancreatic ducts of HFD mice treated by puerarin. Of note, efficacy of puerarin in vivo was suppressed by GLP-1R antagonist exendin9-39, but enhanced by exendin-4 respectively. In cultured mouse pancreatic ductal cells, puerarin induced expressions of insulin and PDX1, upregulated GLP-1R expression and activated ß-catenin and STAT3 subsequently. Expressions of insulin and PDX1 in ductal cells could be blocked by exendin9-39, or ß-catenin inhibitor ICG001, or JAK2 inhibitor AG490. CONCLUSION: These data clarified puerarin ameliorated hyperglycemia of HFD mice via a novel mechanism involved promoting ß-cell neogenesis. Our finding highlights the potential value of puerarin developing as an anti-diabetic agent.

Discovery and characteristics of B cell-like T cells: A potential novel tumor immune marker?

BACKGROUND: CD3 and CD19 are the characteristic surface markers of mature T lymphocytes and B lymphocytes of human respectively. A special subset of immune cells that characteristically expressed the surface markers CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously (CD19+CD3+ cells, hereinafter referred to as B-T cells) was found in the peripheral blood of human, yet it has not been reported in cancer research before. Our aims were to characterize the expression and possible value of B-T cells in cancer patients. METHODS: Flow cytometry was applied to analyse the CD19+CD3+ cells, and laser scanning confocal microscope was utilized to prove co-expressing CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously on the surface of the cells. Then a total of 523 patients with malignant tumor were enrolled in this study, and 177 healthy donors were recruited as the control group. The levels of CD19+CD3+ cells in peripheral blood were measured by flow cytometry, and the differences between the two groups were compared. RESULTS: The healthy donors and cancer patients all had B-T cells in their peripheral blood, but the percentage of B-T cells was 0.16 % ± 0.11 % and 0.58 % ± 0.38 % respectively, showing statistically significant (P < 0.0001). There was no significant correlation between the percentage of B-T cells and lymphocyte subsets (P > 0.05). The percentages of B-T cells in different tumor species were different. The proportion of B-T cells was high in esophageal cancer, non-Hodgkin's lymphoma and lung cancer, but it was low in pancreatic cancer, ovarian cancer and kidney cancer. Meanwhile, there was significant difference between esophageal cancer and kidney cancer (P < 0.001). The distribution of B-T cells in pancreatic cancer and kidney cancer was more concentrated, yet more dispersed in other cancers. Although there was a trend of increase in clinical stage Ⅲ+Ⅳ and a trend of decrease in age above 60 years for breast cancer, gastric cancer and liver cancer, there was no significant difference in the percentage of B-T cells in age, gender, different clinical stages, tumor metastasis, lymph node metastasis, and splenomegaly (P > 0.05). CONCLUSION: The percentage of B-T cells in cancer patients was significantly higher than that of healthy donors. B-T cells maybe play a very complicated role in tumor, whether it could be a potential tumor immune marker or not and what are the specific phenotypes and functions of it to need be further verified.

Correction: Clinical characteristics and prognoses of patients treated surgically for metastatic lung tumors.

[This corrects the article DOI: 10.18632/oncotarget.14822.].

Salidroside, A Natural Antioxidant, Improves ß-Cell Survival and Function via Activating AMPK Pathway.

Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces ß-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on ß-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased ß-cell mass and ß-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm) via reducing NOX2 expression and inhibiting JNK-caspase 3 apoptotic cascade subsequently to protect ß-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in ß-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving ß-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on ß-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on ß-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing ß-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC.

BACKGROUND: Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. OBJECTIVE: To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. METHODS: We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. RESULTS: Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical benefit (CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. CONCLUSION: Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC.

[Negative HBsAg and HBsAb in Women of Child-bearing Age in Mianyang].

OBJECTIVES: To investigate the distribution of women with negative HBsAg and HBsAb at child-bearing age in Mianyang. METHODS: A total of 62 551 women aged 15-49 yr. were selected randomly using a multistage sampling strategy in Mianyang to participate in a questionnaire survey. Blood samples were collected during the survey. HBsAg and HBsAb were detected by enzyme-linked immunosorbent assay (ELISA). Those who were both HBsAg and HBsAb negative were deemed as susceptible to future infection of HBV. RESULTS: Data from 62 035 participants were valid for analysis: 28 460 (45.88%) were both HBsAg and HBsAb negative. Those aged 15-20 yr. had the lowest negative rate. Higher HBsAg and HBsAb negative rates were found in Han (lowest in Tibetan), rural residents, widowed/divorced (lowest in married), peasants (lowest in medical workers), those with a family history of Hepatitis B and without vaccination ( P<0.005). CONCLUSIONS: A high proportion of women at child-bearing age in Mianyang was found to be HBsAg and HBsAb negative. They should be monitored and vaccinated as a priority population in the prevention of mother-to-children infection of hepatitis B.

Clinical characteristics and prognoses of patients treated surgically for metastatic lung tumors.

The clinical characteristics of metastatic lung tumors are not well understood. To explore the surgical indications, surgical modes, and factors that influence postoperative outcomes, we analyzed clinical data from 42 patients with metastatic lung tumors who received surgical treatment at Tianjin Medical University Cancer Institute and Hospital between January 2000 and January 2014. Gender, age, nature of resections, surgical mode, smoking index, disease-free intervals (DFIs), number of metastatic lesions, and lymph node metastases were analyzed. Patients were followed for 6 to 98 months. We found that surgical treatment is feasible for resectable metastatic lung tumors, though postoperative radiochemotherapy had no significant effect on postoperative survival rates among patients with metastatic lung tumors. No patients died perioperatively. The 1-year, 3-year, and 5-year survival rates after surgical resection of metastatic lung tumors were 88.1%, 45.7%, and 34.6%, respectively. Univariate analysis indicated that DFIs and lymph node metastasis correlated with patient prognoses, while multivariate analysis indicated these two variables were independent prognostic factors. Thus surgical treatment may be indicated, depending on patients' specific condition, to lengthen DFIs in patients with metastatic lung tumors with or without evident lymph node metastasis.

[Experience of professor LI Zhidao in the treatment of mental disorders by "regulating the heart and smoothing the liver"].

The experience of Professor LI Zhidao is introduced in the treatment of mental disorders by "regulating the heart and smoothing the liver". In his experience, the basic prescription includes: penetrating needling technique from Neiguan (PC 6) to Jianshi (PC 5), Ximen (PC 4), penetrating needling technique from Qiuxu (GB 40) to Zhaohai (KI 6) and penetrating needling technique at four groups of acupoints on the gallbladder meridian [Hanyan (GB 4) to Xuanlu (GB 5) and Xuanli (GB 6), Qubin (GB 7) to Shuaigu (GB 8), Shuaigu (GB 8) to Tianchong (GB 9), Tianchong (GB 9) to Fubai (GB 10) and Touqiaoyin (GB 11)]. The manipulation with respiration involved is combined with interactive needling technique so that the patients can feel the weak needling sensation at the local acupoint regions during the treatment. In the paper, the concrete clinical cases are introduced to explain this application and the satisfactory efficacy achieved. The therapeutic method provides a new approach to the clinical treatment of mental disorders.

[Distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province].

OBJECTIVE: To understand the distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province, and provide evidences for the development of adult immunization policy. METHODS: From June 2013 to April 2014, a total of 200 929 people aged ≥15 years were selected in Mianyang through stratified cluster random sampling to conduct an interview with standard questionnaire. The blood samples were collected from them for the detection of HBsAg and HBsAb with enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the people surveyed, 13 903 were HBsAg positive (7.0%), 93 763 were HBsAb positive (46.6%), and 93 122 were both HBsAg and HBsAb negative (46.3%). The negative rate of both HBsAg and HBsAb in females (47.1%) was higher than that in males (45.4%). The negative rate of both HBsAg and HBsAb increased with age. The negative rate of both HBsAg and HBsAb was highest in people aged ≥65 years (50.3%) and lowest in people aged 15-24 years (42.9%). The negative rate of both HBsAg and HBsAb was highest in farmers (51.1%) and lowest in medical workers (24.1%). The negative rate of both HBsAg and HBsAb was highest in the widowed (51.1%) and lowest in the unmarried (41.6%). The negative rate of both HBsAg and HBsAb was lower in people with family history of hepatitis B (36.5%) than in people without family history of hepatitis B (46.6%). The negative rate of both HBsAg and HBsAb in Han ethnic group was lower (46.3%) than that in Qiang ethnic group (53.1%), but higher than that in other ethnic groups (43.9%). The negative rate of both HBsAg and HBsAb was higher in rural area (48.9%) than in urban area (43.0%). The negative rate of both HBsAg and HBsAb was lower in people who had received hepatitis B immunization (43.7%) than in people who had received no hepatitis B immunization (47.3%). The differences were all statistical significant (P<0.01). CONCLUSION: The negative rate of both HBsAg and HBsAb was 46.3% in people aged ≥15 years in Mianyang. General population are susceptible to hepatitis B virus infection. It is necessary to develop and implement appropriate hepatitis B immunization strategy for local adult population.

[Clinical experiences of Professor Li Zhi-dao's acupuncture technique at muscle belly for arthralgia].

Professor LI Zhi-dao's acupuncture technique at muscle belly and its clinical experiences for the treatment of arthralgia are introduced. From aspects of TCM, anatomical physiology and sports biomechanics, the theory basis of this technique is explained, while its method is elaborated in details from acupoint selection and manipulation combined with classic medical cases. The acupuncture technique at muscle belly is applied at the muscles which already have pathological changes, avoiding re-stimulation on the pain area. It provides new thinking methods and references for acupuncture to treat arthralgia.

[Direct determination of lead and cadmium in soil by slurry-sampling graphite furnace atomic absorption spectrometry using matrix modification technique].

A method for the direct determination of lead and cadmium in soil by slurry-sampling graphite furnace-atomic absorption spectrometry using NH4 H2 PO4 as matrix modifier was developed. The effects of slurry stability, particle size of sample, matrix modifiers, ashing temperature, atomization temperature and common coexistent components on the signal intensities of lead and cadmium were investigated. The apparent activation energies of lead and cadmium were measured based on the linear relationship between the logarithm value of atomization peak time and atomization temperature. The mechanism of matrix modification was discussed. Under optimized conditions, the detection limit was 9.05 x 10(-10) g x mL(-1) for Pb and 1.76 x 10(-11) g x mL(-1) for Cd. The recoveries were in the range of 91%-97% for Pb and 93%-109% for Cd. The relative standard deviations were in the range of 4.2%-7.8%.