Objective:To effectively quantify and evaluate the quality of different deformation registration algorithms, in order to enhance the possibility of implementing deformation registration in clinical practice.Methods:The Jacobian determinant mean (JDM) is proposed based on the Jacobian determinant (JD) of displacement vector field (DVF), and the Jacobian determinant error (DJDE) is introduced by incorporating the JD of the inverse DVF. The optical flow method (OF-DIR) and fast demons method with elastic regularization (FD-DIR) were tested on nasopharyngeal and lung cancer datasets. Finally, JDM and DJDE with the Jacobian determinant negative percentage (JDNP), inverse consistency error (ICE) and normalized mean square error (NMSE) were used to evaluate the registration algorithms and compare the differences evaluation indicators in different tumor images and different algorithms, and the receiver operating curve (ROC) was analyzed in evaluation.Results:In lung cancer, OF-DIR outperformed FD-DIR in terms of JDM, NMSE, DJDE and ICE, and the difference was statistically significant( z = -2.24, -4.84, t = 4.01, 6.54, P<0.05). In nasopharyngeal carcinoma, DJDE, ICE and NMSE of OF-DIR were superior to FD-DIR, and the difference was statistically significant ( t = 4.46, -7.49, z = -2.22, P<0.05), but there was no significant difference in JDM ( P>0.05). In lung cancer and nasopharyngeal carcinoma, JDNP of OF-DIR was worse than that of FD-DIR, and the difference was statistically significant ( z = -4.29, -4.02, P<0.01). In addition, DJDE is more specific and sensitive on ROC curve (AUC=0.77), and has different performance result for tumor images at different sites. Conclusions:The JDM and DJDE evaluation metrics proposed are effective for deformation registration algorithms. OF-DIR is suitable for both lung cancer and nasopharyngeal carcinoma, while the influence of organ motion on the registration effect should be considered when using FD-DIR.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective:To explore the role of eosinophil associated ribonuclease A family member 2 (Ear2) in the pathogenesis of lupus and its possible mechanisms involved in renal damage by conditional knockout of myeloid cells in mice.Methods:An Ear2 myeloid conditional knockout mouse model was constructed using CRISP/Cas9 technology, and PCR was applied to identify mice genotype. The experiment was divided into 3 groups: CKO+R848 group, control+R848 group, and control group. R848 (Resiquimod) was used to treat the knockout mice and homozygous control mice to evaluate the occurrence of lupus-like features. Quantitative real-time PCR was performed to detect the expression of Toll-like receptor 7/8 (TLR7/8) and its related inflammatory factors in the kidneys of mice. Flow cytometry (FCM) was used to detect the proportion of patrolling monocytes in the kidneys, and immunofluorescence was used to analyze the spatial distribution of Ear2 and PMOs in renal tissues. In addition, R848 was used to stimulate myeloid cells of conditional knockout (CKO) and control mice in vitro, with changes in the proportion of PMOs detected by flow cytometry. Variance (ANOVA) was used to compare the differences between groups, t-test was used for two-by-two comparisons, and one-way analysis of ANOVA was used for comparisons between multiple groupscant. Results:PCR of myeloid conditioned knockout Ear2 mice showed a genotype of Lyz2 ki/wtEar2 fl/fl and significant down-regulation of Ear2 mRNA levels in bone marrow cells of the knockout mice [(1.03±0.26) vs. (0.22±0.15), t=6.65, P<0.001]. Compared with the control+R848 group, lupus related phenotype presentations of mice was improved and the survival rate tended to increase in the CKO+R848 group (6/10 vs. 7/8, χ2=1.51, P=0.220). The pathological results examination suggested that renal lesions of mice in the CKO+R848 group were also attenuated. The expression level of TLR7 was reduced in the renal tissues of CKO+R848 mice [(1.02±0.09) vs. (0.53±0.04), t=5.13, P=0.003], accompanied by a decrease in PMOs infiltration [(62.00±3.37)% vs. (52.36±0.68)%, t=2.80, P=0.023], and immunofluorescence results showed that Ear2 and PMOs were co-localized in renal tissues. In vitro, R848 stimulation caused an increase in the proportion of PMOs in the control group [(3.99±0.59)% vs. (33.48±1.38)%, t=-33.84, P<0.0001], yet had no effect on CKO mice [(14.33±1.72)% vs. (16.10±1.44)%, t=-1.37, P=0.220]. Conclusion:Conditional knockdown of Ear2 attenuates the development of lupus in mice, especially renal impairments, which is related to the inhibition of TLR7 pathway and reduction of local infiltration of PMOs.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Background Some studies have shown that PM_2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM_2.5-induced depression- and anxiety-like behaviors in mice. Objective To observe the effects of PM_2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM_2.5. Methods Eight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM_2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM_2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM_2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. Results The percentage of open-arm entry [M(P₂₅, P₇₅)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (\begin{document}$\bar x \pm s $\end{document}) in the PM group were (2.01±0.90) m and (10.31±1.99) s respectively, shorter than those of the NS group [(3.80±0.89) m, (14.47±3.07) s], the total travelled distance in the PML group [(2.73±1.12) m] was shorter than those of the NS group and the LGG group [(4.21±1.08) m], and the differences were statistically significant (P<0.05). Compared to the NS group, the Simpson index of the PM group significantly increased (P<0.05). Compared to the LGG group, the Simpson index of the PML group significantly decreased (P<0.05). The results of Beta diversity analysis showed that there were differences in the composition of intestinal flora among the four groups of mice. Compared with the NS group and the LGG group, the abundances of Erysipelotrichaceae and Dubosiella in the PM group and the PML group increased, while the abundances of Prevotellaceae_UCG-001 decreased, and the differences were statistically significant (P<0.05). In hippocampus, the level of 5-HT in the PM group [(135.02±10.31) μg·g⁻¹] was lower than those in the NS group [(178.77±43.15) μg·g⁻¹] and the LGG group [(224.85±22.98) μg·g⁻¹], and the level of 5-HT in the PML group [(161.27±15.81) μg·g⁻¹] was lower than that in the LGG group (P<0.05). 5-HT level in hippocampus was significantly positively correlated with the relative abundance of Prevotellaceae_UCG-001 (r=0.6090, P=0.012). The percentage of open-arm entry was significantly negatively correlated with the relative abundance of Dubosiella (r=−0.4630, P=0.023). Conclusion Atmospheric PM_2.5 exposure may cause depression- and anxiety-like behaviors in mice. The observed behavior dysfunction may be associated with the changes in diversity and relative abundance of intestinal flora as well as the decrease of 5-HT level. Such depression- and anxiety-like behaviors are alleviated after adding probiotics.

Objective:To evaluate delayed laparoscopic cholecystectomy (DLC) after percutaneous transhepatic gallbladder drainage (PTGBD) in acute cholecystitis.Methods:Clinical data of 64 patients who were diagnosed moderate (grade Ⅱ) acute cholecystitis by the 2018 Tokyo Guidelines in acute phase and underwent delayed LC at our hospital from Jan 2018 to Jan 2021 were compared between two groups ie PTGBD treatment (21 cases)in acute stage before DLC and DLC without PTGBD group (43 cases). The difficulty score of TG18 was used to evaluated every surgical procedure of the cases by reviewing the operation videos.Results:Patients in DLC after PTGBD group had a longer hospital stay and operation time, more blood lose and higher difficulty score than the DLC without PTGBD group(all P<0.05). There was no statistically significant difference in the conversion rate and morbidity rate between the two groups( P>0.05). Conclusion:This study fails to show there is any if ever benefit of PTGBD before DLC over DLC without PTGBD in the management of Grade Ⅱ acute cholecystitis.

Respiratory mucosal immune system is the body''s first line of defense against infection.Since the outbreak of novel coronavirus disease 2019 (COVID-19) in 2019,nasal mucosal immune vaccine, with its ability to induce cellular, humoral and mucosal triple immune responses, has become a research hotspot.This article focuses on novel coronavirus, with an understanding of its structure and pathogenesis, a brief introduction to the immune mechanism of nasal mucosa, a summary of the different types of nasal mucosal immune vaccines and their clinical research, aiming to provide some theoretical reference for the development of new vaccines, and exploration of the best methods and strategies to combat COVID-19.

Objective:To evaluate the efficacy of combination of toy and cartoon video-assisted admission in preventing agitation during recovery from general anesthesia in preschool children.Methods:Totally 96 children who undergoing elective surgery from July 2018 to October 2019 in Guangzhou Women and Children′s Medical Center were divided into experimental group ( n=48) and control group ( n=48). Two groups were admitted to the general preoperative waiting room for 60 minutes before the operation, and children in the experimental group recieved toy and cartoon video combination intervention, while children in the control group were subjected to routine nursing intervention. The children′s agitation was assessed by using Pediatric Anesthesia Emergence Delirium Scale (PAED) when children entered the post-anesthesia care unit (PACU), 10 minutes after in PACU and leave PACU. In addition, the vital signs such as blood pressure, heart rate, respiratory rate of the two groups were also recorded. Results:The emergence time and duration of PACU stay in the experimental group were (17.19±1.76) minutes and (22.47±2.36) minutes, significantly shortern than in the control group (18.36±2.19) minutes and (23.82±2.62) minutes, the difference was statistically significant ( t values were 2.760, 2.546, P<0.05). 10 minutes after in PACU and out of PACU, the PAED scores, systolic pressure, heart rate, respiratory rate was [7.56±1.86, 4.60±1.19, (108.12±10.19)mmHg, (102.72±8.55) mmHg, (112.91±6.10) times/minute, (106.39±6.75) times/minute, (18.87±1.98) times/minute, (17.49±1.68) times/minute], significantly lower than those in the control group [13.40±1.47, 6.71±2.21, (116.73±14.17)mmHg, (107.62±12.44) mmHg, (121.07±8.07) times/minute, (114.69±5.78) times/minute, (20.96±1.86) times/minute, (18.47±1.63) times/minute], the difference was statistically significant ( t values were 2.162-16.332, P<0.05). Conclusion:Toy and cartoon video combine-assisted admission can reduce the agitation and stable vital signs during recovery from general anesthesia in preschool children.