Objective To investigate the safety and efficacy of Remimazolam combined with nalbuphine in painless endoscopic mucosal resection(EMR)of colorectal polyps.Methods A total of 100 patients who undergo painless colorectal polyp EMR were randomly divided into nalbuphine combined with remimazolam(NR)and nalbuphine combined with propofol(NP),with 50 patients in each group.The mean arterial pressure,heart rate and oxygen saturation were recorded after entry(T0),1min after administration(T1),1min at the beginning of surgery(T2),3min(T3),5min(T4),and at the end of surgery(T5).The frequency of application of vasoactive drugs,their operation time,consciousness vanishing time,recovery time,the times of supplementary sedation,dosage of incidence of nalbuphine,adverse reactions,The satisfaction of doctors and patients were compared.Results The mean arterial pressure of T1,T2,T3,T4 and T5 in the NR group was higher than that in the NP group(P<0.05),and the heart rate of T1 in the NR group was higher than that in the NP group(P<0.05).The incidence of respiratory depression,hypotension,injection pain,the recovery time and the frequency of application of vasoactive drugs in the NR group was lower than that in the NP group(P<0.05).The satisfaction of doctors in the NR group was higher than that in the NP group(P<0.05).There was no significant difference between the two groups in the operation time,oxygen saturation,the times of supplementary sedation,the dosage of incidence of nalbuphineincidence of dizziness,nausea and vomiting,and other adverse reactions(P>0.05).Conclusion Nalbuphine combined with remimazolam can be used safely in the EMR,has few perioperative adverse effects,and is a good choice for painless EMR.

Cluster of differentiation 36 (CD36) is a membrane glycoprotein receptor capable of binding and transporting fatty acid. Nogo-B regulates the metabolism of fatty acids in the liver and affects the development of liver cancer. To date, it remains unclear whether the interaction between CD36 and Nogo-B affects the proliferation and migration of breast cancer cells. In the current study, we aimed to determine whether the interference of CD36 and Nogo-B affects the proliferation and migration of triple-negative breast cancer (TNBC) cells. The results showed that inhibition of CD36 or Nogo-B alone can inhibit the proliferation and migration of TNBC cells, and the inhibitory effect was more pronounced when CD36 and Nogo-B were inhibited simultaneously. Meanwhile, it was found that inhibition of CD36 and Nogo-B expression can inhibit the expression of Vimentin, B-cell lympoma-2 (BCL2) and proliferating cell nuclear antigen (PCNA). In vivo, knockdown of CD36 or Nogo-B in E0771 cells reduced its tumorigenic ability, which was further enhanced by knockdown of CD36 and Nogo-B simultaneously. Mechanistically, inhibition of CD36 and Nogo-B expression can decrease fatty acid binding protein 4 (FABP4) and fatty acid transport protein 4 (FATP4) expression. Moreover, overexpression of CD36 and Nogo-B-induced cell proliferation was attenuated by FABP4 siRNA, indicating that inhibition of CD36 and Nogo-B expression could inhibit the absorption and transport of fatty acids, thereby inhibiting the proliferation and migration of TNBC. Furthermore, inhibition of CD36 and Nogo-B expression activated the P53-P21-Rb signaling pathway which contributed to the CD36 and Nogo-B-inhibited proliferation and migration of TNBC. Taken together, the results suggest that inhibition of CD36 and Nogo-B can reduce the proliferation and migration of TNBC, which provides new targets for the development of drugs against TNBC.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Cell Movement ; Cell Proliferation ; Cell Line, Tumor ; Fatty Acids

Objective To investigate the changing trend of platelet count (PLT) and related influencing factors in patients with hepatitis B virus-related chronic-on-acute liver failure (HBV-ACLF) after artificial liver support system (ALSS) therapy. Methods A total of 152 patients with HBV-ACLF who were hospitalized and treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2018 to November 2021 were included in the study, among whom 102 patients received plasma exchange (PE) and 50 patients received double plasma molecular absorption system combined with low-dose PE, and their clinical data and laboratory marker were measured. The independent samples t -test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and the chi-square test was used for the comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the risk factors for PLT > 50×10 9 /L after ALSS therapy; the receiver operating characteristic (ROC) curve was used to investigate the value of baseline PLT in predicting PLT > 50×10 9 /L after ALSS therapy. Results The patients were mostly middle-aged male adults; among the 152 patients, 70 (46.1%) had liver cirrhosis on admission, 114 (75.0%) received three sessions of ALSS therapy, and 88% had a baseline PLT count of > 50×10 9 /L. There was a significant reduction in PLT from baseline to after ALSS therapy (79.5±47.7 vs 112.5±64.1, t =4.965, P < 0.001), and at 1 week after treatment, PLT increased to the baseline level (97.2±50.7 vs 112.5±64.1, t =1.787, P =0.075). As for the change in PLT from baseline to 1 week after ALSS therapy, the liver cirrhosis group had a significantly greater reduction in PLT than the non-liver cirrhosis group ( U =1986.5, P =0.026), while there was no significant difference between different procedures of ALSS therapy and different sessions of treatment (3-5 sessions) (all P > 0.05). The multivariate logistic regression analysis showed that cirrhosis (odds ratio [ OR ]=3.097, 95% confidence interval [ CI ]: 1.255-7.645, P =0.014) and PLT > 50×10 9 /L at baseline ( OR =0.019, 95% CI : 0.002-0.154, P < 0.001) were independent risk factors for PLT > 50×10 9 /L after ALSS therapy. The ROC curve analysis of baseline PLT showed that PLT > 80.5×10 9 /L at baseline was the optimal cut-off value affecting PLT > 50×10 9 /L after treatment, with an area under the ROC curve of 0.818. Conclusion The influence of ALSS therapy on PLT is temporary, but cirrhotic patients have a weaker PLT generation ability than non-cirrhotic patients. PLT > 80.5×10 9 /L at baseline is the optimal cut-off value to reduce the risk of bleeding after ALSS therapy.

Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.

Objectives:To study the clinical significance of time to positive (TTP) of blood culture for neonatal sepsis.Methods:From August 2016 to June 2019, a retrospective study was conducted in patients with positive blood cultures admitted to the Neonatology Department of our hospital. The patients were assigned into different groups according to the species of pathogen, types of neonatal sepsis and the samples contaminated or not. TTP of different groups were analyzed.Results:A total of 307 cases with positive blood cultures were identified from 10 035 cases with blood culture specimens. Among the 307 cases, 162 were contaminated (the contaminated group) and 145 (1.4%) were diagnosed of neonatal sepsis (the pathogenic group). The proportion of TTP <24 h, 24~<48 h, 48~<72 h and ≥72 h in the 145 sepsis cases were 90.3% (131/145), 7.6% (11/145), 1.4% (2/145) and 0.7% (1/145), respectively. The median TTP was 9.0 h in early-onset sepsis (EOS) group and 11.5 h in late-onset sepsis (LOS) group. The median TTP of the contaminated group was 24.5 (19.9, 30.5)h, which was longer than 11.1 (8.1,16.2)h of the pathogenic group ( P<0.05). The median TTP of Gram (+) group was 14.0 (9.4,18.8)h, which was longer than 9.6 (7.5,11.3)h of Gram (-) group ( P<0.05). The median TTP of fungi group was 32.5 (25.5, 39.0) h, which was longer than 10.6 (8.1, 15.5)h of bacteria group ( P<0.05). Conclusions:Different pathogens has different TTP for neonatal sepsis. If blood culture maintains negative for more than 72 h, empiric use of antibiotics may be discontinued for patients of suspected sepsis without specific clinical manifestations or other lab results.

Objective:To investigate the anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics of patients with warfarin-related major bleeding in the emergency department of a general hospital.Methods:In a registry study from January 2017 to February 2020, 114 cases of warfarin-related major bleeding patients admitted to Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University were enrolled. The descriptive methods were used to analyze anticoagulant causes, hemorrhagic susceptibility factors and clinical characteristics. Patients were divided into the international normalized ratio (INR) overrange group and the INR non-overrange group according to INR value during bleeding. The Chi-square test, Student’s t test, and Wilcoxon rank sum test were used to compare the differences between the INR overrange group and the INR non-overrange group. The Wilcoxon rank sum test and Student’s t test were used to analyze the characteristics of gastrointestinal tract bleeding and cerebral hemorrhage. Results:Warfarin-related major bleeding accounted for 0.36% (114/32 040) of first aid cases and 9.84% (114/1 158) of warfarin-taking cases, respectively. Seventy-seven cases (67.5%) of anticoagulant causes were related to atrial fibrillation (AF) and 32 cases (28.1%) were related to post-operative cardiac valve replacement. Of the bleeding susceptibility factors, HAS-BLED scored at 4.0 (3.0, 5.0), 84 cases (73.7%) had a history of drug use, 77 cases (67.5%) aged older than 65 years old, 65 cases (57.0%) had irregular INR monitoring, and 29 cases (25.4%) had recent increase in dose. Forty cases (35.1%) were gastrointestinal tract bleeding with the lowest hemoglobin (Hb) value and the highest score of HAS-BLED. Twenty-one cases (18.4%) were cerebral hemorrhage with the shortest prothrombin time (PT), the lowest INR value, the highest Hb, and the lowest score of HAS-BLED. Twelve cases (10.5%) died or gave up treatment in critical condition, including 6 cases of cerebral hemorrhage, 5 cases of gastrointestinal tract bleeding, and 1 case of hemoptysis. There were statistically significant differences in previous history of antiplatelet therapy, recent increase in dose, HAS-BLED score and bleeding site between the INR overrange group and the INR non-overrange group (all P<0.05). Conclusions:Among patients with warfarin-related major bleeding, AF and post-operative cardiac valve replacement are the main causes of warfarin anticoagulation. INR overrange is related to the previous history of antiplatelet therapy, recent increase in dose, and the high score of HAS-BLED. The gastrointestinal tract bleeding is the most common, with the lowest Hb value and the highest score of HAS-BLED. Cerebral hemorrhage is the second common, with the shortest PT, the lowest INR value, and the highest Hb. The incidence and mortality rates of warfarin-related major bleeding are relatively high.

Objective:To explore whether the 15-minute retention rate (R15) of indocyanine green (ICG) in the indocyanine green excretion test and the effective hepatic blood flow (EHBF) can predict the occurrence of mild hepatic encephalopathy (MHE).Methods:Using the convenience sampling method, we collected clinic data from 153 patients diagnosed with liver cirrhosis or liver failure from June 2019 to December 2019 in the Third Affiliated Hospital of Sun Yet-sen University in Guangzhou. We screened the MHE patients with the number connect test-A and the digital symbol test, and analyzed the clinical data. By taking different values for R15 and EHBF as cut-off points, the significance of the two factors in predicting MHE is explored respectively.Results:The incidence of MHE was 38.56% (59/153). Single factor analysis showed that the difference of Child-Pugh grade between the MHE group and the non-MHE group was statistically significant ( χ2 value was 7.606, P<0.05), while the differences between cirrhosis and liver failure diagnosis, fasting blood glucose, and serum creatinine were not statistically significant ( P>0.05). When most points between 0.11 and 0.61 were selected as normal and abnormal cut-off points of R15, R15 had statistical significance ( P<0.05) and when R15 selected 0.18, it was most significant (Fisher exact test P=0.00024). When most points between 0.08 and 0.76 were selected as normal abnormal cut-off points of EHBF, EHBF had statistical significance ( P<0.05) and when EHBF selected 0.25, it was most significant (Fisher exact test P=0.00022). Through Logistic stepwise regression analysis, the risk factors for MHE were R15 and EHBF. The ROC curve was used to illustrate the predictive effects of two factors on MHE. Conclusions:The incidence of MHE in patients with cirrhosis or liver failure is high. When R15≥0.18 or EHBF≤0.25 L/min, R15 and EHBF in indocyanine green excretion test can better predict the occurrence of MHE than Child-Pugh classification, and can be help to evaluate and manage patients in time.

Protein kinase CK2 is a common, evolutionarily conserved and ubiquitous protein kinase. In recent years, increasing evidences have shown that CK2 has a variety of phosphorylated protein substrates, which play important roles in growth, development and various diseases. Therefore, CK2 may participate in these physiological processes by regulating the phosphorylation of these substrates. This article briefly reviewed the structural characteristics of protein kinase CK2 and its physiological functions in growth, development, immunity, formation of tumor and other diseases, in order to provide knowledge basis for further research on the regulatory mechanism of CK2 and potential applications of its inhibitors.
Casein Kinase II/metabolism* ; Phosphorylation ; Proteins

Objective:To evaluate the measurement agreement of Roche 25(OH)D immunoassay(evaluation method) with LC-MS/MS (reference method).Methods:A total of 909 residual serum samples from routine health check participants were collected from May to June in 2019. 25(OH)D concentrations were measured by evaluation method and LC-MS/MS, respectively. Passing-bablok regression, intraclass correlation coefficient (ICC), Bland Altman plots and Kappa test were used to analyze the consistency and bias on the results derived from the two measurement methods.Results:The 25(OH)D concentration derived from evaluation method was significantly different from those from LC-MS/MS method ( P<0.001). Slope of regression for evaluation method and LC-MS/MS was 0.962(95% CI 0.919-1.007), while intercept was -0.185 (95% CI -1.191-0.745). The ICC was 0.765 (95% CI 0.735-0.792). Altman plot showed that the average deviation between evaluation method and LC-MS/MS was -0.902 ng/ml (0.300%). The coincidence rate of evaluation method′s judgment of vitamin D sufficiency, insufficiency and deficiency with LC-MS/MS was 83.39%, and the weighted Kappa values was 0.790. Conclusion:Roche automatic 25(OH)D immunoassay shows acceptable correlation and agreement with LC-MS/MS, however, it is to note that the deviation between immunoassay and LC-MS/MS may lead to wrong judgment of vitamin D nutritional status. It is recommended that each laboratory should establish own corresponding reference values for 25(OH)D concentrations derived from these two methods.

Objective:To analyze the cognition and willingness of family physicians on contracted service, and to explore the implementation obstacles and feasible strategies of implementing contracted service of family physicians from the perspective of suppliers.Methods:From July to October 2020, 850 family physicians in community health service centers or township health centers in three cities of Shandong Province were investigated by questionnaire survey and key person interview. Descriptive analysis and binary logistic regression model were used to analyze the willingness of family physicians to provide contracted service. Through questionnaire survey and key person interview, the implementation obstacles and service optimization strategies of family physicians were discussed.Results:791 valid questionnaires were obtained, of which 688(87.0%) approved the implementation of family physician contract service, and 679(85.8%) expressed willingness to provide family physician contract service. Marital status, recognition of service policy, satisfaction of service operation effect, optimistic degree of service development prospect and residents′ first choice of illness were the factors influencing family physician′s service willingness.Conclusions:We should effectively improve the family doctor′s service intention and promote the efficient and orderly implementation of family doctor′s contract service policy through enriching policy supporting measures, innovating the application of " Internet plus" , increasing personnel training, optimizing performance appraisal work and creating favorable public opinion environment.