ObjectiveTo investigate the correlation between iron metabolism parameters and various syndrome types of unstable angina pectoris （UAP）. MethodsA cross-sectional study was conducted from October 2021 to October 2023， encompassing 213 patients diagnosed with UAP at Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences. Additionally， 30 healthy individuals were selected as control cases. Single-factor analysis was used to investigate the differences in clinical data among different Traditional Chinese Medicine （TCM） syndrome types of UAP and their correlation with iron metabolism indices. The study conducted a comparative analysis of the aforementioned clinical data among patients with and without heat-toxic and blood-stasis syndrome. Logistic regression was used to analyze the correlation between TCM syndrome types and related factors. The receiver operator characteristic （ROC） curve was employed to assess the predictive value of iron metabolism indices， along with their sensitivity and specificity. ResultsCompared to those in the control group， serum iron （SI） and serum ferritin （SF） levels were significantly increased in the UAP group （P<0.01）， while transferrin （TRF） and total iron binding capacity （TIBC） levels were decreased （P<0.01）. However， there was no significant difference in unsaturated iron binding capacity （UIBC）. Multivariate binary Logistic regression analysis identified apolipoprotein A1 （ApoA1）， homocysteine （HCY）， high-sensitivity C-reactive protein （hs-CRP）， and SF as independent influencing factors for the UAP patients （P<0.05， P<0.01）. Additionally， statistically significant differences were observed in SI， SF， TRF， and TIBC among 213 patients with different TCM types （P<0.01）. Patients with heat-toxic and blood-stasis syndrome had higher SI and SF values than those without the syndrome （P<0.01）， while their TIBC and TRF values were lower （P<0.01）. Multivariate binary logistic regression analysis showed that SI and LDL-C levels were closely associated with the differentiation of heat-toxic and blood-stasis syndrome. ConclusionUAP patients often experience iron metabolism disorders， and the heat-toxic and blood-stasis syndrome are significantly correlated with iron metabolism parameters. The SI and LDL-C levels have high specificity and sensitivity in diagnosing heat-toxic and blood-stasis syndrome.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

Objective:To investigate the expression level between AT-Rich Interaction Domain 1A(ARID1A) in intrahepatic cholangiocarcinoma (ICC) and the correlation with tumor microenvironment.Methods:The clinicopathological and survival data of 110 ICC patients undergoing radical hepatectomy in Peking University People's Hospital from Jan 2015 to May 2021 were retrospectively analyzed. Immunohistochemical staining was used to detect the expressions of ARID1A , programmed cell death 1 ligand 1( PD-L1) in tumor tissues , programmed cell death protein 1(PD-1) and cluster of differentiation 8(CD8) in the microenvironment. The relationship between ARID1A expression and PD-L1, PD-1, CD8 protein expression was analyzed.Results:Twenty seven patients did not express ARID1A, absence of ARID1A was associated with high PD-L1, PD-1 and CD8 expression ( P<0.05). Multivariate analysis showed ARID1A expression, preoperative CEA level,preoperative CA19-9 level, lymph node metastasis and tumor number were independent risk factors. Conclusion:Absent expression of ARID1A suggests poor prognosis of ICC patients, high expression of PD-L1,PD-1 and CD8 protein in ICC tumor microenvironment with ARID1A-deficient expression suggests a possible prognosis benefit by using anti-PD-1, anti-PD-L1 and other immunotherapy regimens.

Objective:To evaluate the risk of HBV recurrence after liver transplantation in patients with end-stage hepatitis B related liver disease, and to explore the indications for antiviral therapy withdrawal.Methods:The data of HBV DNA, cccDNA in liver puncture tissues and peripheral blood in 31 patients after liver transplantation was retrospectively analyzed.Results:Among the 31 patients, 15 (48%) had detectable and quantified HBV DNA in liver biopsy tissue, while their HBV related serological indicators were negative, suggesting an occult HBV infection in some patients. The study found 15 out of 19 cases who were taking Entecavir were cccDNA negative (78.9%), compared to 5 out of 12 cases (41.6%) in Lamivudine regiment ( P=0.03). Conclusions:Hidden HBV infection can be detected by amplifying cccDNA and HBV DNA in liver puncture tissue by using ddPCR. Entecavir is superior to lamivudine in the clearance of cccDNA.

Objective:To compare the application effect of remote intelligent rehabilitation system and conventional rehabilitation in rehabilitation of patients with rotator cuff injury following minimally invasive arthroscopic surgery.Methods:A retrospective cohort study was used to analyze the clinical data of 47 patients with rotator cuff injury admitted to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January to July 2022, including 18 males and 29 females; aged 45-65 years [(56.7±6.3)years]. All patients underwent minimally invasive arthroscopic surgical repair of rotator cuff rupture. After surgery, 25 patients underwent self-rehabilitation with conventional education (conventional rehabilitation group), and 22 patients underwent systematic rehabilitation with remote intelligent rehabilitation system (remote rehabilitation group). Constant shoulder score, University of California at Los Angeles (UCLA) shoulder score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score and visual analog score (VAS) were compared between the two groups on the day of admission, 4, 8, 12 weeks after surgery and at the last follow-up. Shoulder MRI was applied at 6 weeks after surgery to compare the degree of intra-articular effusion and bone marrow edema between the two groups. The shoulder range of motion of the two groups was compared at 12 weeks after operation. The satisfaction with the rehabilitation of the two groups was compared at the last follow-up.Results:All the patients were followed up for 6-10 months [(8.5±2.2)months]. There was no significant difference in Constant shoulder score, UCLA shoulder score, SAS score, SDS score and VAS between the two groups on the day of admission (all P>0.05). There was no significant difference in Constant score, UCLA score and SAS score between the two groups at 4 weeks after surgery (all P>0.05). The values of SDS score and VAS at 4 weeks after surgery were (31.8±6.6)points and (3.6±1.1)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(40.5±5.6)points and (4.7±1.3)points] (all P<0.05). The values of Constant score, UCLA score, SAS score, SDS score and VAS at 8 weeks after surgery were (62.5±5.5)points, (18.5±3.3)points, (20.5±4.7)points, (22.5±4.6)points and (2.5±0.6)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(41.3±4.7)points, (15.3±3.1)points, (28.5±4.8)points, (38.5±3.7)points and (3.3±1.3)points] ( P<0.05 or 0.01). The values of Constant score, UCLA score, SAS score and SDS score at 12 weeks after surgery were (85.4±6.4)points, (32.2±3.8)points, (13.6±2.8)points and (18.4±3.9)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(60.3±6.7)points, (25.2±4.1)points, (21.5±4.9)points and (26.7±6.6)points] (all P<0.05), while there was no significant difference in VAS between the two groups ( P>0.05). At the last follow-up, there were no significant differences in Constant score, UCLA score, SAS score, SDS score and VAS between the two groups (all P>0.05). MRI of the shoulder joint at 6 weeks after surgery indicated that the degree of intra-articular effusion in the shoulder joint and bone marrow edema of the proximal humerus in the remote rehabilitation group was significantly reduced than that in the conventional rehabilitation group. At 12 weeks after surgery, the remote rehabilitation group had better shoulder range of motion than the conventional rehabilitation group ( P<0.05 or 0.01). At the last follow-up, the satisfaction with the rehabilitation of the remote rehabilitation group was better than that of the conventional rehabilitation group ( P<0.01). Conclusion:For patients with rotator cuff injury who undergo minimally invasive arthroscopic surgery, postoperative application of remote intelligent rehabilitation system, in comparison with the conventional rehabilitation system, can help to facilitate shoulder function recovery, anxiety and depression improvement and pain relief in the early stage, reduce shoulder soft tissue and bone marrow edema of the shoulder, and increase shoulder range of motion and patients′ satisfaction with the rehabilitation.

Objective:To analyze the differentially expressed gene (DEG) in rats with sepsis-induced exogenous acute respiratory distress syndrome (ARDS) and explore the early diagnosis and protective mechanism of sepsis-induced ARDS at the transcriptome level.Methods:Twelve 6 to 8 weeks old male Sprague-Dawley (SD) rats were randomly divided into lipopolysaccharide (LPS) induced sepsis-induced ARDS model group (model group, intraperitoneal injection of LPS 15 mg/kg) and control group (intraperitoneal injection of the same volume of normal saline), with 6 rats in each group. RNA was extracted from the left lung tissue of the two groups, and the paired-end sequencing mode of the illumina Hiseq sequencing platform was used for high-throughput sequencing. The DESeq2 software was used to screen DEG with | log 2 (fold change, FC) | ≥ 3 and P < 0.001. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEG. STRING and CytoScape software were used to construct a protein-protein interaction (PPI) network and screen key genes. The peripheral blood mononuclear cell (PBMC) of 20 septic patients admitted to the emergency and critical care medical department of Lianyungang First People's Hospital from March to November 2021 and 20 age-matched healthy people in the same period were isolated and extracted, and the key genes were verified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Results:A total of 286 DEG were screened, including 202 up-regulated genes and 84 down-regulated genes. GO enrichment analysis showed that DEG was mainly involved in biological processes such as neutrophil chemotaxis migration, antibacterial humoral response, host immune response, and humoral immune response. KEGG analysis showed that DEG mainly played a biological role through interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and chemokine signaling pathway. In PPI analysis, a total of 262 node proteins were screened, and the interaction relationship was 852 edges. The first 15 key genes were IL-6, TNF, IL-10, IL-1β, chemokine ligand 1 (CXCL1), CXCL10, chemokine receptor 3 (CXCR3), CXCR2, CXCL9, chemokine ligand 7 (CCL7), CXCL11, CCL1, CXCL13, CCL12, and CCL22. Five representative key genes were performed on PBMC of blood samples from septic ARDS patients and healthy controls by RT-qPCR. The results showed that their expression was significantly higher than that in the healthy controls [IL-6 mRNA (2 -ΔΔCt): 2.803±1.081 vs. 0.951±0.359, TNF mRNA (2 -ΔΔCt): 2.376±0.799 vs. 1.150±0.504, CXCL10 mRNA (2 -ΔΔCt): 2.500±0.815 vs. 1.107±0.515, CXCR3 mRNA (2 -ΔΔCt): 1.655±0.628 vs. 0.720±0.388, CCL22 mRNA (2 -ΔΔCt): 1.804±0.878 vs. 1.010±0.850, all P < 0.05], and the trends were consistent with the RNA-Seq results. Conclusion:Biological processes such as chemotactic migration and degranulation of inflammatory cells, cytokine immune response, and signal pathways such as CXCL10/CXCR3 and IL-17 play important roles in the occurrence and development of sepsis-related exogenous ARDS, which would provide new ideas and targets for further study of lung injury mechanisms and clinical prevention and treatment.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.