68Ga-DOTATATE/18F-FDG two-day low-dose total-body PET/CT imaging is increasingly employed to facilitate the diagnosis,prognosis,and heterogeneity assessment of neuroendocrine neoplasms.We present a consensus on operational guideline for a two-day combined imaging from experts in low-dose/ultra-low-dose total-body PET/CT from several domestic medical institutions.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Production internship is an important teaching tache for undergraduate students to carry out engineering training by using professional skills, and it is a key starting point for fostering application-oriented talents in biotechnology. The Course Group of 'production internship of biotechnology majors' of Binzhou University is investigating application-oriented transformation for local regular colleges and universities, as well as fostering high-level application-oriented talents. By taking green fluorescent protein (GFP) polyclonal antibody as an example, the reform and practice on teaching content, teaching mode, assessment method, continuous improvement of curriculum were carried out. Moreover, the characteristics of the Yellow River Delta-Binzhou Biotechnology & Pharmaceutical Industrial Cluster were taken into account to intensify academic-enterprise cooperation. On one hand, this Course Group designed and rearranged the course contents, carried out essential training through online resources and platforms such as virtual simulation, and recorded, tracked and monitored the progress of production internship through practical testing and software platforms like 'Alumni State'. On the other hand, this Course Group established a practice-and application-oriented assessment method in the process of production internship and a dual evaluation model for continuous improvement. These reform and practices have promoted the training of application-oriented talents in biotechnology, and may serve as a reference for similar courses.
Humans ; Internship and Residency ; Curriculum ; Students ; Biotechnology

Objective:To investigate the relationship between 18F-FDG PET/CT Lugano lymphoma response evaluation criteria and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) at the end of chemotherapy. Methods:A total of 131 patients with DLBCL (63 males, 68 females, age (50.3±17.0) years) who underwent 18F-FDG PET/CT at the end of chemotherapy in the Fourth Hospital of Hebei Medical University from July 2013 to January 2021 were analyzed retrospectively. 18F-FDG PET/CT Lugano lymphoma response evaluation criteria was used to evaluate the response (complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD)). Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier survival analysis was used for univariate analysis of clinical parameters and imaging parameters, and Cox proportional hazards regression model was used for multivariate analysis to explore related factors affecting the prognosis of patients with DLBCL. Results:The median follow-up time was 35.47 months for 131 patients with DLBCL. The 5-year PFS rate was 57.3%(75/131), and the 5-year OS rate was 84.0%(110/131). There were 74 cases of CR, 37 cases of PR and 20 cases of PD. Univariate analysis showed that the Lugano lymphoma response evaluation criteria was the influencing factor of PFS and OS (PFS, χ2=72.25, P<0.001; OS, χ2=11.97, P=0.003). Deauville score (DS) of patients with DLBCL was also the influencing factor for PFS ( χ2=62.46, P<0.001) and OS ( χ2=19.95, P<0.001). Ann Arbor stage, Eastern Cooperative Oncology Group physical state (ECOG PS) score and international prognostic index (IPI) were the influencing factors for PFS ( χ2 values: 10.31-15.80, all P<0.05). Ann Arbor stage, ECOG PS score, number of extranodal organ involved, β 2 microglobulin, and IPI were the influencing factors for OS ( χ2 values: 4.97-30.57, all P<0.05). Cox multivariate analysis showed that Lugano lymphoma response evaluation criteria, Ann Arbor stage and ECOG PS score were independent prognostic factors for PFS (relative risk ( RR) and 95% CI: 8.841(4.764-16.405), 1.434(1.111-1.852), 2.125(1.205-3.746), P values: <0.001, 0.006, 0.009) and OS ( RR(95% CI): 3.276(1.304-8.235), 9.728(2.216-42.669), 2.506(1.040-6.039), P values: 0.012, 0.003, 0.041). Conclusion:18F-FDG PET/CT Lugano lymphoma response evaluation criteria can precisely evaluate the prognosis of patients with DLBCL at the end of chemotherapy.

OBJECTIVE: To analyze the molecular characteristics of a ABO subgroup. METHODS: The ABO phenotype was determined with the tube method. Exons of the ABO gene were analyzed by Sanger sequencing, and haplotypes of exons 6 and 7 were analyzed by cloning sequencing. RESULTS: By forward typing, the red blood cells showed 3+ agglutination reaction with anti-A and 4+ agglutination with anti-B. A weak reaction with A1 cells and no agglutination reaction with B, O cells by the reverse typing. Sequencing results showed heterozygosity including c.297A>G, c.467C>T, c.526C>G, c.608A>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C, c.930G>A. Cloning sequencing revealed a c.608A>G variant in the A allele compared with the ABO*A1.02. CONCLUSION A new variant site of subtype A of c.608G variation has been identified.
ABO Blood-Group System/genetics* ; Alleles ; Exons ; Genotype ; Heterozygote ; Phenotype

Objective To investigate the early resuscitation effect of hemoglobin-based oxygen carriers (HBOC) in rats with uncontrolled hemorrhagic shock.Methods 170 Sprague-Dawley (SD) rats were randomly divided into five groups:lactate Ringer solution (LR) control group,whole blood control group,and 0.5％,2.0％,5.0％ HBOC groups,with 34 rats in each group.The uncontrolled hemorrhagic shock model in SD rats was reproduced by cutting off the splenic artery branch,and induced mean arterial pressure (MAP) reducing to 40 mmHg (1 mmHg =0.133 kPa).The corresponding solution was infused after model reproduction in each group,maintaining MAP at 50 mmHg for 1 hour,then completely ligating and hemostasis,and maintaining MAP at 70 mmHg for 1 hour and 80 mmHg for 1 hour respectively,after maintaining MAP 80 mmHg,all were supplemented with LR to 2 times blood loss volume.The survival rate and blood loss rate were observed in 16 rats in each group,hemodynamics parameters including MAP,left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (+dp/dtmax) were determined in another 10 rats,and cardiac output (CO) and tissue oxygen supply (DO2) were observed in the rest 8 rats.Results ① When resuscitation by LR alone,the blood loss rate of animals was as high as 60％ to 70％.Compared with the LR control group,whole blood recovery could significantly reduce the blood loss rate before hemostasis in uncontrolled hemorrhagic shock rats [(46.6 ± 4.5)％ vs.(62.3 ± 4.0)％,P ＜ 0.01];0.5％,2.0％,5.0％ HBOC could significantly decrease the blood loss rate,especially in 5.0％ HBOC group with significant difference as compared with that in the LR control group [(45.6±4.1)％ vs.(62.3±4.0)％,P ＜ 0.01].② When LR was used alone for resuscitation,the rats died quickly and survived for a short time.Only one rat survived for 12 hours,and no rat survived for more than 24 hours.Compared with the LR control group,whole blood resuscitation could improve the survival rate of uncontrolled hemorrhagic shock rats,and the survival time was significantly prolonged (hours:20.4± 4.6 vs.3.5 ± 1.1,P ＜ 0.01);0.5％,2.0％ and 5.0％ HBOC also significantly prolonged the survival time of rats.The 5.0％ HBOC group had the best effect,4 rats survived in 24 hours,and the survival time was significantly longer than that of the LR control group (hours:18.4 ± 4.0 vs.3.5 ± 1.1,P ＜ 0.01),and it was the same as the whole blood control group.③ Compared with pre-shock,CO,DO2 and hemodynamic parameters of uncontrolled hemorrhagic shock rats were significantly decreased,and the above parameters were gradually increased with the prolongation of rehydration time.Compared with the LR control group,whole blood resuscitation could significantly increase CO and DO2,and improve hemodynamics in rats with uncontrolled hemorrhagic shock at different time points.Three concentrations of HBOC could also increase CO,DO2 and other hemodynamic parameters of rats at 1 hour of maintaining MAP of 80 mmHg after hemostasis and 1 hour and 2 hours after resuscitation.The effect of 5.0％ HBOC group was more significant than that of the LR control group with statistically significant difference [CO (× 10-3,L/min):72.84±2.84 vs.63.11±2.38 at 1 hour of maintaining MAP of 80 mmHg,70.25±4.55 vs.59.88 ± 9.31 at 1 hour after resuscitation,71.51 ± 2.90 vs.53.24 ± 6.32 at 2 hours after resuscitation;DO2 (L· min-1 · m-2):271.9± 13.5 vs.159.1 ±25.4 at 1 hour of maintaining MAP of 80 mmHg,261.0± 15.0 vs.145.7±20.1 at 1 hour after resuscitation,249.6± 12.0 vs.107.4± 18.2 at 2 hours after resuscitation;MAP (mmHg):82.1±2.1 vs.74.0±2.8 at 1 hour of maintaining MAP of 80 mmHg,107.5±9.3 vs.64.0±5.7 at 1 hour after resuscitation,104.0±9.7 vs.73.0±4.2 at 2 hours after resuscitation;LVSP (mmHg):128.6±7.9 vs.103.8±0.8 at 1 hour of maintaining MAP of 80 mmHg,129.3±± 15.0 vs.99.4±0.0 at 1 hour after resuscitation,127.5± 11.3 vs.97.4±0.0 at 2 hours after resuscitation;+dp/dt max (mmHg/s):6 534.2±± 787.6 vs.5 074.0± 71.7 at 1 hour of maintaining MAP of 80 mmHg,5 961.5 ±± 545.4 vs.4 934.5 ± 510.2 at 1 hour after resuscitation,5 897.4± 350.5 vs.4 534.7 ±489.2 at 2 hours after resuscitation,all P ＜ 0.05].Conclusions HBOC infusion prolonged the survival time,increased survival rate,and improved hemodynamics,cardiac function and tissue oxygen supply in a dose-dependent manner in the early stage of uncontrolled hemorrhagic shock.The recovery effect of 5.0％ HBOC was similar to that of the whole blood.

Objective To investigate the effect of EZH2 on apoptosis and radiosensitivity of squamous cell carcinoma of tongue.Methods Tongue squamous carcinoma cells Tca-8113 were transfected with small interfering RNA of EZH2 (EZH2 siRNA1,EZH2 siRNA2) and its negative controls (siRNA-NC),the expression levels of EZH2 were detected by RT-PCR and Western blot and EZH2 siRNA2 was used for further studied since its better interference efficiency.The cells with siRNA transfection were irradiated with 8 Gy doses,and cell proliferation was detected by MTT,apoptosis was detected by flow cytometry,the expression of p-STAT3,STAT3 and Cleaved Caspase-3 was detected by Western blot.In addition,the cells were irradiated with 0,2,4,6,and 8 Gy to detect radiosensitivity by cell colony formation assay.Results EZH2 siRNA1 and EZH2 siRNA2 decreased the expression of EZH2 in Tca-8113 cells and EZH2 siRNA2 had a better interference efficiency (tmRNA =8.660,PmRNA ＜ 0.01;tprotein =2.883,Pprotein ＜0.05).The apoptotic rate in the EZH2 siRNA group was (29.90 ± 1.64)％,and was increased by 8 Gy irradiation to (38.17 ± 1.59) ％ (t =4.742,P ＜ 0.05).At the same time,EZH2 siRNA reduced the level of p-STAT3,but promoted the expression of Cleaved Caspase-3 protein,and enhanced the sensitivity of Tca-8113 cells to 1.668-times of control.Conclusions Interfering EZH2 could promote apoptosis,inhibit proliferation and increase radiosensitivity of squamous cell carcinoma of tongue.

Keratinized mucosa in oral cavity plays an important role in periodontal health. The defect of keratinized mucosa may increase the risks of complication of oral implant surgery and restoration. Graft of keratinized tissue and connective tissue are still the gold standard for treating keratinized mucosa defect now. The current research focus on how to modulate non-keratinized mucosa to highly-efficient and minimally-invasive keratinized mucosa. Keratinocytes are critical components of oral mucosa and its final differentiation into keratinized mucosa is controlled by the connective tissue microenvironment involving a variety of molecules and ions. To fully understand keratinized differentiation of keratinocyte, this review focuses on its influence factors and possible mechanisms under the differentiation.

Objective To explore the feasibility and clinical application value of total laparoscopic radical resection of Ⅳ-type hilar choangiocarcinoma. Methods Clinical data of 2 patients receiving total laparoscopic radical resection of Ⅳ-type hilar choangiocarcinoma in Hunan Provincial People's Hospital from April 2015 to December 2015 were analyzed retrospectively. The informed consents of both patients were obtained and the local ethical committee approval was received. Case 1, male, 73 years old, hospitalized for icteric skin and sclera for more than 1 month. Case 2, female, 62 years old, hospitalized for icteric skin and sclera for more than 2 months. The admitting diagnosis were both Ⅳ-type hilar choangiocarcinoma. The bilateral hepatic ducts and left portal vein were invaded by tumor in the 2 cases. Before the operation, the patients received symptomatic and supportive treatments for liver protection, jaundice alleviation etc., and then received total laparoscopic radical resection of hilar choangiocarcinoma. The lymph nodes were resected from far to near, the common bile duct was dissected and cut off, the left and caudate lobe was resected, hilar bile duct plasty and Roux-en-Y bilioenterostomy were performed. Results Operations were performed successfully in both patients and the digestive tract was reconstructed. The operative duration were 430, 410 min respectively, the intraoperative blood loss was 800, 600 ml respectively. No perioperative complication was observed.Two patients received abdominal enhanced CT examination 1 year after operation, no tumor recurrence or metastasis was observed. Conclusion Total laparoscopic radical resection of hilar choangiocarcinoma is safe and feasible, in which hemihepatectomy or extended hemihepatectomy including caudate lobe, lymphadenectomy, bile duct plasty and biliary-enteric reconstruction can be performed.