Objective:To explore the differences of microenviroment between peri-implant tissue and oral mucosal tissue.Methods:The gene chip data GSE43744 was downloaded from the GEO database,bioinformatics tools were used to analyze the differentially ex-pressed genes between the peri-implant tissue and normal oral mucosal tissue in rat.Results:1315 differentially expressed important genes,including 797 upregulated genes and 518 downregulated genes,were screened out.Gene enrichment analysis showed that com-pared with normal oral mucosal tissue,the gene expression of innate immune activity,cell activation,inflammatory response,and func-tional expression related to external and bacterial stimuli in peri-implant tissue were significantly upregulated,while that of extracellular matrix tissue,adhesion,extracellular matrix polysaccharides,response to mechanical stimuli and response to toxic substances was sig-nificantly downregulated.Meanwhile,multiple molecular functions and biological pathways related to T cells were highly expressed,which may play an important role in the peri-implant microenvironment.In addition,PPI network was constructed,and screened 7 core genes including FCER1G,TYROBP,PTPRC,ITGB2,AIF1,EMR1 and RAC2,which may be target genes for studying peri-implant microenvironment.Conclusion:There is a significant difference of microenvironment characteristics between peri-implant tissue and o-ral mucosa.The target genes screened using PPI network may be the key to future research on the peri-implant microenvironment.

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

Objective:To evaluate the value of curative effect in neuromyelitis spectrum disease (NMOSD) based on circulatory function evaluation of intracerebral glymphatic system by using diffusion tensor imaging analysis along the perivascular space.Methods:The clinical and imaging data of 23 patients diagnosed with NMOSD at Tianjin Medical University General Hospital from March 2018 to December 2019 were retrospectively analyzed in this study. The clinical data included expanded disability status scale (EDSS), average relapse rate (ARR) and retinal nerve fiber layer (RNFL) thickness at baseline and 1 year follow-up after treatment. Among the 23 NMOSD patients, there were 22 females and 1 male, aged from 21 to 71 (45±13) years old. All the patients underwent MR scans at both baseline and 1 year after treatment, and the scanning sequences included cerebral 3D-T 1WI, T 2WI, diffusion tensor imaging and cervical spinal sagittal 3D-T 2WI, and the cervical spinal cord volume and bilateral diffusion tensor imaging analysis along the perivascular space index (ALPS index) were calculated. The partial correlation test was used to analyze the correlations between ALPS index and the clinical indicators such as EDSS, ARR, and bilateral RNFL, with the control variables as gender, age, years of education and course of disease. The multiple linear regression model was used to analyze the independent predictors for ALPS index and EDSS after treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic value of NMOSD treatment outcome by using ALPS index. Results:When controlling for gender, age, years of education and course of disease, there were significant negative correlations between right ALPS index and EDSS ( r=-0.50, P=0.048), bilateral average ALPS index and EDSS ( r=-0.53, P=0.034), left ALPS index and ARR ( r=-0.58, P=0.018), while there was significant positive correlations between right ALPS index and RNFL ( r=0.88, P=0.008) at 1 year follow-up after treatment. Multiple linear regression analysis showed that cervical spinal cord volume was an independent impact factor of bilateral average ALPS indexes (β=0.24, 95%CI 0.10-0.38, P=0.002), and bilateral average ALPS indexes (β=-3.22, 95%CI -5.97--0.48, P=0.024) and right RNFL (β=-0.05, 95%CI -0.08--0.02, P=0.002) at baseline were the independent impact factors of EDSS after treatment. ROC curve analysis showed that the bilateral average ALPS index at baseline had the best efficacy in predicting the curative effect of NMOSD patients with AUC=0.92. Conclusions:After treatment, NMOSD patients with severe clinical disability, high frequency of disease attack, poor visual performance, and severe cervical spinal cord atrophy have more serious impairment of intracerebral glymphatic system circulatory function. The ALPS index could help in predicting the clinical curative effect of NMOSD patients.

Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans ; Killer Cells, Natural ; Interferon-gamma ; Apoptosis ; Autoimmune Diseases ; Cytokines

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.

Obesity is a global public health problem that imposes a heavy economic burden on society. The current main strategies for treating obesity include lifestyle interventions, pharmacological treatments, endoscopic treatments and metabolic surgery. With the development of medical technology, weight reduction by intragastric occupancy devices represented by intragastric balloons and intragastric capsules are gradually emerging. Intragastric balloons are used to reduce weight by occupying the volume of the stomach with balloons filled with different volumes of gas or liquid, among which ReShape, Orbera, Obalon, Elipse and Spatz balloons are gradually used in patients with mild to moderate obesity due to their non-invasive, high safety and reusable advantages. Intragastric capsules are recommended in overweight and obese patients for weight loss through hydrogels with transient superabsorbent swelling properties and completely noninvasive. Both approaches achieve weight loss by limiting gastric volume, increasing satiety and reducing food intake. Despite the presence of adverse gastrointestinal events associated with nausea, vomiting, and abdominal distention, they offer new ideas for the non-invasive clinical treatment of obesity.
Humans ; Capsules ; Weight Loss ; Obesity/surgery* ; Overweight ; Stomach/surgery*

Ascosphaera apis spores containing a dark-colored pigment infect honeybee larvae, resulting in a large-scale collapse of the bee colony due to chalkbrood disease. However, little is known about the pigment or whether it plays a role in bee infection caused by A. apis. In this study, the pigment was isolated by alkali extraction, acid hydrolysis, and repeated precipitation. Ultraviolet (UV) analysis revealed that the pigment had a color value of 273, a maximum absorption peak at 195 nm, and a high alkaline solubility (7.67%) and acid precipitability. Further chemical structure analysis of the pigment, including elemental composition, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, mass spectrometry, and nuclear magnetic resonance (NMR), proved that it was a eumelanin with a typical indole structure. The molecular formula of melanin is C₁₀H₆O₄N₂, and its molecular weight is 409 Da. Melanin has hydroxyl, carboxyl, amino, and phenolic groups that can potentially chelate to metal ions. Antioxidant function analyses showed that A. apis melanin had a high scavenging activity against superoxide, hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and a high reducing ability to Fe³⁺. Indirect immunofluorescence assay (IFA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses showed that A. apis melanin was located on the spore wall. The spore wall localization, antioxidant activity, and metal ion chelating properties of fungal melanin have been suggested to contribute to spore pathogenicity. However, further infection experiments showed that melanin-deficient spores did not reduce the mortality of bee larvae, indicating that melanin does not increase the virulence of A. apis spores. This study is the first report on melanin produced by A. apis, providing an important background reference for further study on its role in A. apis.
Animals ; Antioxidants/pharmacology* ; Larva ; Melanins ; Molecular Structure ; Onygenales

Downstaging treatment by local therapy combined with systemic therapy before liver transplantation for patients with recurrent hepatocellular carcinoma (HCC) can control tumor progression and reduce tumor burden, which resulting in reducing the push-out rate of patients during the waiting period for liver transplantation, providing an oncological observation window, enabling patients of beyond Milan criteria downstaged with better survival benefit. The authors introduce the clinical experience of a case with recurrent HCC of beyond Milan criteria who under-went liver transplantation after receiving atezolizumab plus bevacizumab combined with local therapy. Results show the patient achieving pathological complete remission without postoperative rejection and obtaining a good prognosis with life status improved.

Objective:To study the intraoperative surgical factors which influenced non-immediate postoperative tracheal extubation (IPTE) after liver transplantation.Methods:The clinical data of all liver transplant recipients operated at the Qilu Hospital of Shandong University from January 2011 to July 2019 were reviewed. Patients who returned to a surgical ward with a tracheal cannula or who underwent re-intubation within 48 hours after IPTE because of hypoxemia were assigned to the cannula-preserving group (non-IPTE). The remaining liver recipients were assigned to the control group (IPTE). Univariate and multivariate logistic regression analysis were used to analyze the risk factors influencing IPTE.Results:Of 70 patients enrolled into this study, there were 30 patients in the cannula-preserving group (with 25 males, 5 females, and age of 51.8±7.3). And 40 patients in the control group (with 35 males, 5 females, and age of 48.4±9.6). Univariate logistic regression analysis showed anhepatic phase >45 min, blood loss >800 ml and intraoperative hypothermia were related with non-IPTE after liver transplantation(all P<0.05). Multivariate logistic regression analysis revealed anhepatic phase >45 min ( OR=3.972, 95% CI: 1.193-13.220, P=0.025) and intraoperative hypothermia ( OR=23.682, 95% CI: 2.434-230.438, P=0.006) increased the risk of unsuccessful IPTE. Conclusion:A long anhepatic phase and intraoperative hypothermia were surgical risk factors affecting non-IPTE after liver transplantation. Surgeons should avoid patients having hypothermia and a prolong anhepatic phase during liver transplantation.