Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Gout is a metabolic disorder characterized by elevated uric acid levels， often caused by purine metabolism disturbances or abnormalities in uric acid （UA） excretion. Currently， western medicine is the primary treatment approach for gout， but it often comes with significant side effects. Traditional Chinese medicine （TCM） has gained significant development in the field of gout treatment due to its safety and effectiveness. This article aimed to explore TCM strategies in the management of gout， providing insights for the development and application of TCM in the field of gout treatment. Relevant literature retrieved from PubMed， Web of Science， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP databases was systematically analyzed with such keywords as "Chinese herbal medicine"， "traditional Chinese medicine"， "TCM"， and "gout". The findings suggest that TCM can treat gout through a syndrome differentiation approach that encompasses four pathological mechanisms： phlegm， blood stasis， dampness， and deficiency， simultaneously addressing both excess and deficiency syndromes in gout. Based on the pathological characteristics of four syndromes， namely dampness-heat retention， blood stasis-heat obstruction， phlegm-turbidity obstruction， and liver and kidney Yin deficiency， TCM adopts specific treatment approaches including clearing heat and promoting diuresis， activating blood and resolving stasis， resolving phlegm and reducing turbidity， and nourishing the liver and kidneys. These targeted approaches have proven to be effective in gout management. The main mechanisms of TCM in gout management include inflammation resistance ［regulating inflammatory pathways such as tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， interleukin-8 （IL-8）， and other chemokines， as well as inflammatory signaling pathways like nuclear factor-kappa B （NF-κB） and NOD-like receptor protein 3 （NLRP3）］， uric acid reduction （modulating uric acid transporters and inhibiting xanthine oxidase （XOD） activation）， antioxidant stress mitigation （suppressing reactive oxygen species and regulating nitric oxide， malondialdehyde， and other oxidative markers）， and immune system regulation.

Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1（Der f 1/IGF-1 NPs） and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-β in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-β and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant（P<0.001）. After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant（P<0.001）. Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.
Humans ; T-Lymphocytes, Regulatory/metabolism* ; Interleukin-10/metabolism* ; Insulin-Like Growth Factor I ; Transforming Growth Factor beta ; Nanoparticles/chemistry* ; Particle Size ; Drug Carriers/chemistry*

Objective:To explore the mediating role of mindfulness in part-time nursing faculty between intrinsic motivation and work engagement.Methods:A total of 376 part-time nursing faculty were investigated with Work Preference Inventory, Five Facet Mindfulness Questionnaire-Short Form and Utrecht Work Engagement Scale. SPSS 25.0 statistical software was used to perform t test on the data. Results:The intrinsic motivation of part-time nursing faculty positively predicted work engagement ( β=0.74, P<0.001). The positive predictive effect of intrinsic motivation on job engagement was weaker than before ( β=0.55, P<0.001). Mindfulness as an intermediary variable reduced the positive predictive effect of intrinsic motivation on work engagement from 0.979 to 0.504. The indirect effect of intrinsic motivation on work engagement through mindfulness was significant (path coefficient=0.50, P<0.001), and the intermediary effect accounted for 48.51% of the total effect. Conclusion:Mindfulness plays an intermediary role between intrinsic motivation and work engagement of part-time nursing faculty. Paying attention to the mindfulness level of part-time nursing faculty plays a positive role in improving their work engagement level.

Objective:To explore the effect of breathing exercises on motor, balance, respiration and ability in the activities of daily living (ADL) of patients with Parkinson′s disease.Methods:Sixty patients with idiopathic Parkinson′s disease who met the inclusion criteria were divided at random into a control group and a treatment group, each of 30. Both groups received routine drug therapy and 60 minute of rehabilitation training daily, including core muscle group control training, relaxation training, joint motion training, posture training, balance function training, gait training and facial muscle control training. There were 3 sessions a week for 24 weeks. The treatment group was also given breathing exercises, including training in abdominal breathing with the expiration time twice the inspiration time and inspiratory muscle training. The abdominal breathing training included 15 abdominal breaths, repeated twice after a 2-minute break; the inspiratory muscle training required 10 respirations and expirations at the maximum volume, repeated twice after an interval of 2 minutes. The training lasted 24 weeks, five times a week. The subjects′ motor functioning, balance, walking, respiration and daily living ability were evaluated before the treatment and after 12 and 24 weeks of treatment using the Parkinson′s Disease Rating Scale (part III) (UPDRS ⅲ), the Berg Balance Scale (BBS), the 6-minute walk test (6MWT), walking distance and the modified Barthel Index (MBI). Forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC) and their ratio (FEV 1%) were also observed. Results:After 12 weeks of treatment, significant improvement was observed in the average UPDRS iii, BBS, 6MWT, MBI, FEV 1, FVC and FEV 1% results of both groups, but the improvement in the treatment group was significantly greater on average. After another twelve week the average UPDRS iii, BBS, 6MWT, MBI, FEV 1, FVC and FEV 1% results of the treatment group had improved significantly more than those of the control group. Conclusion:Breathing exercises can significantly improve the motor function, balance, walking, respiratory function and ADL ability of persons with Parkinson′s disease.

Objective:To screen the neutralizing epitope of enterovirus 71 (EV71) and determine the specific minimum amino acid sequence that triggers immunity for providing a theoretical basis for the development of synthetic peptide vaccines.Methods:EV71 neutralizing antibody-specific binding clones were panned and sequenced using a phage display random 12-peptide library to obtain the key sequences of neutralizing epitopes. A series of peptides containing the key sequences with N-terminal acetylation (AC) and C-terminal linking to Keyhole limpet hemocyanin (KLH) were synthesized. Serum samples were collected after immunizing mice with the modified peptides. Then the immunogenicity of the peptides and the neutralizing activity of serum samples were analyzed by Western blot, ELISA and neutralization test.Results:After three rounds of panning, cloning and sequencing, KQEKDL was identified as the key motif. The serum samples collected from the mice immunized with the modified series of peptides containing key motifs had different degrees of binding ability to EV71 and VP1 protein. The serum samples of mice immunized the synthetic peptide containing only the minimum key motif (AC-KQEKDL-KLH) had the strongest response to the other three peptides and EV71 and the highest neutralizing titer.Conclusions:The EV71 neutralizing epitope was successfully screened using the phage display random peptide library. The key motif of KQEKDL might be the specific minimum amino acid sequence that triggered the immune system. This study provides a theoretical basis for better understanding the immune response mechanism, evaluating the immunogenicity of the antigens and further research and development of polypeptide vaccines.

Objective:To investigate the efficacy and side effects of amnion stent implanted in lacrimal duct for the lacrimal duct obstruction diseases (LDOD).Methods:A randomized controlled clinical trial was adopted.Seventy-two eyes of 72 patients with LDOD treated in Jiangxi Provincial People's Hospital from June 2014 to January 2015 was randomized into the experiment group and the control group with amnion stent or silicone tube retrogradely implanted according to grouping in accordance with block randomization with 36 eyes in each group.All patients were performed irrigation of lacrimal passage at 3 and 6 months postoperatively to compare the patency rate of lacrimal duct and side effects between the two groups.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Jiangxi Provincial People's Hospital (No.2014-002).Results:The patency rate of lacrimal duct was 91.7%(33/36) and 80.6%(29/36) at 3 months postoperatively in the experimental and control group, respectively.Although the difference was obvious, there was no statistical significance ( P=0.307). The patency rate of lacrimal duct was 88.9%(32/36) and 75.0%(27/36) at 6 months postoperatively in the experimental and control groups, respectively.Similarly, the difference was obvious, however there was no statistical significance ( P=0.220). At 3 months and 6 months postoperatively, the incidence of epiphora in the experimental group was lower than that in the control group, it was significantly different ( Z=2.729, P=0.006), and there was no significant difference at 6 months postoperatively ( Z=1.921, P=0.055). At 6 months follow-up period, the attack rate of side effects, such as dacryon congestion and exudation, was 2.8%(1/36) and 13.9%(5/36) in the experiment and control groups, respectively, however, the difference was no statistical significance ( P=0.199). Conclusions:The implantation of amnion stent in lacrimal duct for LDOD is effective, and the patency rate of lacrimal duct is not lower than that of the implantation of silicone tube in the lacrimal duct.

Purpose: This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). Results: Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. Conclusion Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Objective To compare the relationship between the enzyme‐linked immunosorbent assay(ELISA) reagent and West‐ern blot(WB) confirmation reagent for analyzing the quality lever of human T‐cell lymphotropic virus(HTLV) detection reagent . Methods The WB confirmation reagent was used to detect anti‐HTLV antibody in 156 human serum samples of ELISA prelimina‐ry screening positive .The ELISA cut‐off value(optimal value) was selected by using the two‐graph receiver operating characteristics (TG‐ROC) analytical method .The two‐by‐two table analysis was constructed to analyze the consistency of results detected by the two methods ,moreover the McNemar test was used to evaluate the consistency of detection results .The quality level of HTLV de‐tection reagent was comprehensively evaluated .Results Among 156 serum samples of ELISA preliminary screening positive ,only 40 samples were positive by the WB confirmation ,and other 116 samples were negative .The sensitivity and specificity of ELISA de‐tection reagent obtained by TG‐ROC analysis were 97 .5% and 45 .7% respectively ,the TG‐ROC test also indicated that the detec‐tion results had significant difference between ELISA and WB(P<0 .05) .By adjusting the cut‐off value ,the sensitivity and specific‐ity of ELISA were increased to 88 .8% (parametric method) .In the comparison of the parametric method and the non‐parametric method ,the obtained areas under the curve(AUC) was 0 .923 5(parametric method) ,their results were basically consistent .Conclu‐sion Although above results indicate that the detection results of ELISA reagent are different from those of WB ,but adjusting the cut off value can increase its sensitivity and specificity ,thus increases the reliability of diagnosis result .

Objective With the isocentric C-arm (Iso-C) three-dimensional computerized navigation system,cadaveric pelvic specimens were used to imitate double screw fixation of the symphysis pubic.Practicability and safety of the screw trajectory were examined postoperatively by local cadaveric dissections and imaging tests.Methods Pelvic specimens were harvested from 8 male and 7 female adult cadavers.Double screw placement in symphysis pubic was performed using the Iso-C three-dimensional navigation and entry point and safety trajectory was achieved.With the detailed local dissection postoperatively,distances from screw entry and exit points to unilateral structures (spermatic cord,femoral artery and vein,femoral nerve,obturator artery and vein,obtrurator nerve,and so on) were measured respectively.After complete removal of surrounding soft tissues of the specimen with only bony structure kept,the entry angle and length were calculated.Accuracy of double screw fixation of symphysis pubic was further checked using X-ray and CT.Results Entry point of the first screw was at the junction of unilateral pubic tubercle and transitional site of superior pubic ramus.Mean angle of the first screw with the horizontal plane was (7.7 ± 1.9) ° in men and (8.1 ± 1.7) ° in women.Mean angle between the first screw and coronal plane was (7.8 ± 1.8)° in men and (7.7 ±2.0)° in women.Entry point of the second screw was in the same place in the contralateral pubic tubercle.Mean angle between the second screw and horizontal plane was (30.6 ± 4.0) ° in men and (30.8 ± 3.4) ° in women.Mean angle between the second screw and coronal plane was (9.1 ± 3.0)°in men and (9.2 ± 3.3)°in women.Conclusions With the three-dimensional computerized navigation system,the bony channels of double screws implanted in the symphysis pubic are achieved and reliable.Percutaneous double screw fixation is feasible to treat the pubic symphysis diastasis.