ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

Objective An exploratory study of the mechanisms for achieving successful aging at work of clinicians in public hospitals by applying grounded theory and proposing appropriate management recommendations.Methods 24 medical staff from 5 public hospitals in Hubei and Shandong Provinces were interviewed in semi-structured interviews by using purposive sampling methods from June to August in 2023.The interview records were coded,analyzed and integrated with grounded theory.Results Through open coding,spindle coding and selective coding,204 original concepts,47 categories,16 main categories and 5 core category related to model of the mechanism for achieving successful aging at work of clinicians.Conclusion Successful aging at work of senior clinicians encompasses five main areas:physical and mental health,work adaptation,relationships and legacy,internal and external compensation,and value realization.Organizational support factors,individual job crafting affect successful aging at work of senior clinicians by meeting the psychological needs,achieving effective resource management,and promoting person-job matching;individual characteristic factors play a moderating role;job crafting mediates the effect of organizational support factors on successful aging at work among clinicians.

Objective An exploratory study of the mechanisms for achieving successful aging at work of clinicians in public hospitals by applying grounded theory and proposing appropriate management recommendations.Methods 24 medical staff from 5 public hospitals in Hubei and Shandong Provinces were interviewed in semi-structured interviews by using purposive sampling methods from June to August in 2023.The interview records were coded,analyzed and integrated with grounded theory.Results Through open coding,spindle coding and selective coding,204 original concepts,47 categories,16 main categories and 5 core category related to model of the mechanism for achieving successful aging at work of clinicians.Conclusion Successful aging at work of senior clinicians encompasses five main areas:physical and mental health,work adaptation,relationships and legacy,internal and external compensation,and value realization.Organizational support factors,individual job crafting affect successful aging at work of senior clinicians by meeting the psychological needs,achieving effective resource management,and promoting person-job matching;individual characteristic factors play a moderating role;job crafting mediates the effect of organizational support factors on successful aging at work among clinicians.

Objective To explore the effects of long non-coding RNA(lncRNA)small nucleolar molecule RNA host gene 12(SNHG12)targeting inhibition of miR-495-3p/phospholipinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway on the proliferation,migration and invasion of prostate cancer cells.Methods The expressions of SNHG12 and miR-495-3p in prostate cancer tissues and cells(LNCaP,C4-2,DU145)were detected with real-time fluorescence quantitative PCR(qRT-PCR).After DU145 cells were divided into si-NC,si-SNHG12,si-SNHG12+anti-miR-NC and si-SNHG12+anti-miR-495-3p groups,the expressions of SNHG12 and miR-495-3p were detected with qRT-PCR;the targeting relationship between SNHG12 and miR-495-3p was determined with dual luciferase assay;cell proliferation was assessed with MTT assay;cell migration and invasion were evaluated with Transwell assay;the protein expressions of proliferating cell nuclear antigen(PCNA),N-cadherin,and E-cadherin were detected with Western blot.Results The expressions of SNHG12 were significantly increased,while the expression of miR-495-3P was significantly decreased in prostate cancer tissues and cells(LNCaP,C4-2,DU145)(P＜0.05).Knockdown of SNHG12 decreased DU145 cell activity,lowered the protein expressions of PCNA and N-cadherin,reduced the number of migrating and invading cells,but increased the protein expression of E-cadherin(P＜0.05).SNHG12 targeted and negatively regulated miR-495-3p,and down-regulation of miR-495-3p reversed the effects of SNHG12 knockdown on the proliferation,migration and invasion of prostate cancer cells.Compared with the si-NC group,the si-SNHG12 group had significantly decreased expressions of p-PI3K and p-Akt(P＜0.05).Compared with the si-SNHG12+anti-miR-NC group,the si-SNHG12+anti-miR-495-3p group had significantly increased protein expressions of p-PI3K and p-Akt(P＜0.05).Conclusion lncRNA SNHG12 can promote the proliferation,migration and invasion of prostate cancer cells through targeted inhibition of miR-495-3p/PI3K/Akt signaling pathway.

Objective:To establish a method for the simultaneous determination of 22 elements, including beryllium, vanadium, chromium, manganese, iron, calcium, magnesium, barium, cobalt, cadmium, copper, zinc, arsenic, selenium, titanium, strontium, nickel, molybdenum, tin, antimony, thallium and lead, in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) .Methods:In September 2023, the analysis conditions were determined by optimizing the detection mode of the instrument, the pretreatment mode and the dilution factor of the samples, etc. Whole blood samples were diluted with a mixture of 0.1% nitric acid and 0.05% triton X-100, and centrifuged at 2000 r/min by high-speed centrifuge for 2 min. The supernatant was taken into inductively coupled plasma mass spectrometer to determine the content of 22 elements, and the detection limit and precision of the method were analyzed.Results:The 22 elements had a good linear relationship in their respective measurement ranges ( r=0.9991-0.9999), the detection limit ranged from 0.003 μg/L to 0.012 mg/L. The intra-batch precision ranged from 0.5% to 7.2%, the inter-batch precision ranged from 0.4% to 9.4%, and the average recoveries ranged from 80.6% to 114.9%. Conclusion:ICP-MS method has a good effect on the determination of 22 elements in whole blood. The method is fast and simple, and can be used for clinical detection of multiple elements in whole blood.

Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Exosomes are cell-secreted/derived vesicular nanoparticles that mediate a novel form of intercellular communication. Cell secreted mRNA and microRNAs(miRNAs) can undergo functional transfer between cells with exosomes and be delivered to recipient cells as endogenous miRNAs, while regulating multiple target genes or signals. The intercellular communication mediated by exosomes and intestinal microbiome-host cell communication are involved in the pathogenesis and development of inflammatory bowel disease(IBD). This paper review the role of exosomes in the mode of cell communication, and discuss the pathogenesis, progression, therapeutic and diagnostic role of exosomes in IBD, as well as its clinical application prospects, in perspective of intercellular communication.