Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

Objective To explore the diagnosis and treatment strategies for elderly patients with ground-glass opacity (GGO). Methods The imaging features and postoperative pathological findings of the elderly patients with pulmonary GGO receiving surgery in our hospital from 2017 to 2019 were retrospectively analyzed. The patients were divided into an elderly patient group and a non-elderly patient group based on their age. Results Finally 575 patients were included in the study. There were 281 elderly patients, including 83 males and 198 females, with an average age of (67.0±5.3) years. There were 294 non-elderly patients, including 88 males and 206 females, with an average age of (49.1±7.3) years. Compared with the non-elderly patients, elderly GGO patients showed the following distinct clinical features: long observation time for lesions (P=0.001), high proportion of rough edges of GGO (P<0.001), significant pleural signs (P＜0.001) and bronchial signs (P＜0.001), and high proportion of type Ⅱ-Ⅳ GGO (P<0.001), lobectomy type (P=0.013), and invasive lesions reported in postoperative pathology (P<0.001). There was no statistical difference in the average hospital stay between the two groups (P=0.106). Multivariate logistic regression analysis showed that GGO diameter and GGO type were the main factors affecting the operation. Observation time, GGO diameter, GGO type and pleural signs were the main influencing factors for postoperative pathological infiltrative lesions. The cut-off value of GGO diameter in predicting infiltrating lesions was 10.5 mm in the elderly patients group. Conclusion The size and type of GGO are important factors in predicting invasive lesions and selecting surgical methods. Elderly patients with radiographic manifestations of type Ⅱ-Ⅳ GGO lesions with a diameter greater than 10.5 mm should be closely followed up.

[Objective] To compare next generation sequencing (NGS) library construction technology between probe hybridization capture and amplicon methods, and analyze the influencing factors of HLA genotyping resolution level and its prospects in clinical applications. [Methods] A total of 207 clinical samples with known typing results and samples from the proficiency testing plan were selected. The conformity rate of HLA genotyping results, allele coverage and typing data analysis indicators were confirmed, and the effects of two library construction methods on the level of HLA genotyping discrimination were compared. [Results] The concordance rate of 207 samples with the feedback results of PT or prior well-characterized HLA genotypes was 100%. Among them, 91 samples were captured using hybridization probe capture method. Compared with the original amplicon method, the hybridization probe capture method can distinguish the alleles of DRB1 and DPB1 that cannot be determined in 13 samples. The allelic imbalance of DRB1, DPA1, and DQB1 loci in 6 samples was resolved. Three samples were found to have missed detection of alleles at the DQA1 and DQB1 loci. [Conclusion] The performance indicators of hybridization probe capture and amplicon performance confirmation meet the requirements of clinical detection of HLA genotyping, which provides an experimental method and basis for clinical application.

Objective : To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD) and its nano-formulations on depression-like behaviors in mice. Methods : A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS). A total of 55 mice were randomly assigned into several groups: for the long-term study, a control group(Con), a model group(LPS), a cannabidiol group(CBD), a nano-cannabidiol group(NCBD), and a sertraline(SER) group, each consisting of 7 mice. In the short-term study, mice were divided into four groups: the Con group, LPS group, CBD group, and NCBD group, with 5 mice in each group. Except for the Con group and LPS group, which were given distilled water, the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulationviaoral gavage. The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors inmice. Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex, and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2), ionized calcium binding adaptor molecule-1(Iba-1), and interleukin-1β(IL-1β) in the prefrontal cortex. Results : In the long-term experiment, the LPS group exhibited a significant reduction in shuttle times(P<0.05), an increase in immobility time(P<0.01), and a decrease in the number and length of myelin sheaths(P<0.05) compared to the Con group. Compared to the LPS group, the depressive behaviors in the CBD, NCBD, and SER groups were significantly alleviated(P<0.01), and the number and length of myelin sheaths increased(P<0.05). In the short-term experiment, compared to the Con group, the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05), downregulated SIRT2 expression(P<0.01), and upregulated Iba-1 and IL-1β expression(P<0.01). The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05), an increase in SIRT2 expression(P<0.01), and a decrease in Iba-1 and IL-1β expressions(P<0.05) compared to the LPS group. Conclusion CBD and its nano-formulations effectively mitigate anxiety and depression-like behaviors in mice. The underlying mechanisms may be associated with the reversal of SIRT2 protein expression, demyelination changes, microglial activation, and the levels of inflammatory factors in the prefrontal cortex.

Objective:To establish a linkage prediction model for human leukocyte antigen (HLA) DPA1-DPB1 and validate it by using clinical data and follow-up data from unrelated allogeneic hematopoietic stem cell transplantation donors and recipients, and to explore the clinical application value of the prediction model in transplantation prognosis.Methods:This is a retrospective study. Leveraging the artificial neural network algorithm of NetMHCⅡpan and the DPA1-DPB1 haplotype linkage database of the Chinese population established in our previous research, and incorporating the amino acid FASTA data of DPA1-DPB1 of all known sequences newly published by the Latest International Immunogenetics/Human Leukocyte Antigens, 47 DPA1-DPB1 linkage models were established. Employing next-generation sequencing technology based on the hybridization capture library construction method, HLA genotyping tests for HLA-A, -B, -C, DRB1, DQB1, DQA1, DRB3/4/5, DPB1, and DPA1 (9 loci) were performed on 250 donor-recipients pairs who underwent unrelated-donor hematopoietic stem cell transplantation in the Department of Hematology of the First Affiliated Hospital of Soochow University between January 2016 and September 2021. HLA typing data and clinical information of transplant donors and recipients were retrospectively analyzed to assess and predict the impact of permissive and non-permissive linkage mismatches of DPA1-DPB1 on transplantation prognosis. The Kaplan-Meier method with the log-rank test was applied to compare the survival curves of overall survival (OS) rates between different groups. Additionally, a competing risks model was utilized to compare the cumulative incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease and non-relapse mortality (NRM) across groups. The area under the receiver operating characteristic curve was employed to compare the predictive performance of the established prediction model with that of the T-cell epitope (TCE) model.Results:According to the different hydrophilic and hydrophobic properties of amino acids, the DPA1-DPB1 linkage model is categorized into types Ⅰ-Ⅳ: type I consists of 6 hydrophobic types at P1-P8 plus hydrophilic type at P9; type Ⅱ includes 17 hydrophobic types; type Ⅲ comprises 9 amphiphilic types; and type Ⅳ consists of 15 hydrophilic types. According to the prediction model, DPA1-matched and DPB1-mismatched donor-recipient cases were classed into P1-matched or P1-mismatched groups. Compared with fully matched DPA1 and DPB1 cases, P1-mismatched patients had a 2-year OS rate of 75% (12/16) versus 96.2%(25/26) (χ2=4.13, P=0.04), and a NRM rate of 4/16 versus 0 (χ2=7.05, P<0.01). However, there was no statistically significant difference in the 2-year OS and NRM rates compared to DPA1 and DPB1 cases ( P>0.05). The prediction model established in this study demonstrated a larger area under the receiver operating characteristic curve for predicting the 2-year OS rate compared with the DPB1 TCE model ( Z=0.71, P=0.48). In donor-recipient cases where both DPA1 and DPB1 were mismatched, the 2-year OS rates decreased and the NRM increased in both P1-matched and P1-mismatched cases compared with fully matched DPA1 and DPB1. Moreover, P1-mismatched patients had a worse prognosis compared to P1-matched patients. Conclusion:The DPA1-DPB1 linkage prediction model established based on high-throughput next-generation sequencing technology can be used to predict the impact of HLA-DP mismatches on OS and NRM in transplantation, and the prediction performance is superior to the TCE model.

Objective:To explore the effect of progressive case teaching based on Omaha system in standardized training for new nurses.Methods:Using convenience sampling method, 58 new nurses from Yantai Affiliated Hospital of Binzhou Medical University from January to December 2021 were selected as control group, and 58 new nurses from January to December 2022 were selected as experimental group. Experimental group received progressive case teaching based on Omaha system, while control group received routine standardized training. Both groups received training for six months. After six months of training, the academic performance, clinical thinking ability, and satisfaction of the two groups were compared.Results:After intervention, experimental group scored higher in various dimensions of academic performance and clinical thinking ability, as well as satisfaction scores with the teacher, teaching methods, and teaching effectiveness, compared to the control group, with statistical differences ( P<0.05) . Conclusions:The progressive case teaching based on Omaha system in standardized training for new nurses can improve academic performance, enhance clinical thinking abilities, and gain recognition from new nurses.

Objective:To investigate the influence of the interaction between gastric cancer (GC) cell-derived exosomes and hepatic Kupffer cells on GC with liver metastasis and analyze the potential mechanism.Methods:Cells with high hepatic metastatic potential (MKN 45-HL) were constructed from a parental GC cell line (MKN 45) using a nude mouse model and methods of viral transfection and flow sorting. Exosomes were collected using ultra-centrifugation and characterized by electron microscopy, nanoparticle tracking system and Western blot. A nude mouse model of liver metastasis induced by GC cell-derived exosomes was constructed, and the development of liver metastases was monitored by live imaging. The regulatory effects of GC cell-derived exosomes on macrophage polarization were assessed by cell culture, qRT-PCR, and immunofluorescence staining. Using the omics analysis of exosomal miRNA and qRT-PCR, the molecular targets by which exosomes specifically promoting macrophage M2 polarization were screened and validated.Results:GC cell-derived exosomes were mainly concentrated in the liver, most of which were ingested by intrahepatic macrophages, and could promote macrophages to M2 polarization in both in vitro culture and nude mice. Both groups of mice trained with MKN 45 and MKN 45-HL exosomes showed obvious liver metastases after mouse forestomach carcinoma (MFC) cells injection through the spleen, and MKN 45-HL exosomes showed a much stronger ability to promote hepatic macrophage M2 polarization and liver metastasis of MFC cells. Moreover, the miRNA omics analysis revealed a lot of differentially expressed miRNAs between MKN 45-derived and MKN 45-HL-derived exosomes. The expression of miR-519a-3p increased significantly in the exosomes derived from MKN 45-HL cell line and the clinical serum of GC patients with liver metastasis. It was found that miR-519a-3p could be internalized by macrophages through exosomes delivery. Furthermore, the miR-519a-3p in exosomes from patient′s serum had a predictive value for GC with liver metastasis and was closely associated with the prognosis of GC patients with liver metastasis. Conclusions:GC cell-derived exosomes trigger M2-like polarization of hepatic Kupffer cells via miR-519a-3p, thus promoting the progression of liver metastasis in GC and playing a critical role in shaping the pre-metastatic liver niche in gastric cancer. This study provides a new perspective on the mechanism of GC with liver metastasis and reveal potential targets for future therapeutic strategies.

ObjectiveTo clarify the intervention effect of Osteoking （OK） in rats with myofascial pain syndrome （MPS） and preliminarily explore the pharmacological mechanism of OK in relieving chronic pain from the perspective of anti-inflammatory disease. MethodThe 60 SD rats were divided into normal group， model group， low， medium， and high dose OK groups （0.66， 1.31， 2.63 mL·kg^-1）， and positive celecoxib group （21 mg·kg^-1）. The MPS rat model was established by beating combined with the centrifugal exercise method， and the OK and celecoxib were given at the same time. SMALGO paw pressure pain manometer detected the shock pain point tenderness threshold of rats， and the Von-Frey needle and acetone stimulation method detected the mechanical hyperalgesia threshold and cold hyperalgesia stimulation response respectively. Eight weeks and 10 weeks after modeling， the spontaneous discharge state and convulsion response of MPS rats were determined by electromyograph （EMG） instrument. The gait changes of MPS rats were detected using a CatWalk gait analyzer. The expression levels of interleukin-1 β （IL-1β）， tumor necrosis factor-α （TNF-α）， substance P （SP）， and bradykinin （BK） were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of nuclear transcription factor-κB （NF-κB） inhibiting protein α （IκBα）， phosphorylates （p）- IκBα， NF-κB p65， and p-NF-κB p65 were detected in MPS rats by Western blot. The positive expression of p-NF-κB p65 was detected by immunofluorescence. ResultCompared with the normal group， the model group shows 100% positive rates for EMG signal and local convulsions response at both the 8th and 10th weeks. The tenderness threshold and mechanical hyperalgesia threshold are significantly reduced. Cold hyperalgesia score is significantly increased， and gait is abnormal. The expression levels of serum and trigger points IL-1β， TNF-α， SP， BK， p-IκBα， and p-NF-κB p65， as well as the positive expression intensity of p-NF-κB p65 are significantly increased （P<0.01）. Compared with the model group， the positive rate of EMG detection and local convulsion response is significantly reduced in the medium and high dose OK groups （P<0.05）. The tenderness threshold and mechanical hyperalgesia threshold increase significantly in the medium and high dose OK groups， and the cold hyperalgesia score is significantly reduced in the high dose OK group （P<0.01）. The standing time， swing time， and walking period are significantly increased. The swing speed， maximum contact area， and maximum contact intensity are significantly decreased in the high dose OK group （P<0.05）. Moreover， the protein expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 are significantly reduced in the medium and high dose OK groups （P<0.05，P<0.01）. The positive expression intensity of p-NF-κB p65 is significantly decreased in the high dose OK group （P<0.01）. ConclusionThe mechanism of OK in relieving the pain in trigger points of MPS and improving gait abnormalities is related to the downregulation of the NF-κB p65 inflammatory signaling pathway to reduce the expression of inflammatory factors and pain mediators in blood and trigger point tissue.

Objective    To analyze the pathological manifestations and imaging characteristics of bronchiolar adenoma (BA). Methods    The clinical data of 11 patients with BA who received surgeries in our hospital from January 2019 to September 2020 were retrospectively analyzed, including 5 males and 6 females aged 40-73 (62.40±10.50) years. The intraoperative rapid freezing pathological diagnosis, postoperative pathological classification, cell growth pattern, nuclear proliferation index Ki-67 and other immunohistochemical staining combined with preoperative chest CT imaging characteristics were analyzed. Results    The average preoperative observation time was 381.10±278.28 d. The maximum diameter of imaging lesions was 5-27 (10.27±6.34) mm. Eight (72.7%) patients presented with irregular morphology of heterogeneous ground-glass lesions, and 3 (27.3%) patients presented with pure ground-glass lesions. There were 10 (90.9%) patients with vascular signs, 8 (72.7%) patients with vacuolar signs, 1 (9.1%) patient with bronchus sign, 3 (27.3%) patients with pleural traction and 9 (81.8%) patients with burr/lobular sign. The surgical methods included sub-lobectomy in 10 patients and lobectomy in 1 patient. Five (45.5%) patients were reported BA by intraoperative frozen pathology. The postoperative pathological classification included 8 patients with distal-type and 3 patients with proximal-type, and the maximum diameter of the lesions was 4-20 (8.18±5.06) mm. Eight (72.7%) patients showed characteristic bilayer cell structure under microscope, and 10 (90.9%) patients showed thyroid transcription factor 1 expression in pathological tissues. The expression of NapsinA in intracavity cells was found in 9 (81.8%) patients. The Ki-67 index of the lesion tissue was 1%-5% (3.22%±1.72%). Conclusion    The pathological features and imaging findings of BA confirm the premise that BA is a neoplastic lesion. However, to identify BA as a benign or inert tumor needs more clinical data and evidence of molecular pathological studies.