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

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.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

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.

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.

Background Bromadiolone is the second-generation anticoagulant rodenticide widely used all over the world. Exposure to bromadiolone in early life stage can lead to neurodevelopmental toxicity, but its toxic mechanism of neurodevelopment is not clear so far. Objective To investigate the developmental neurotoxicity and mechanism of bromadiolone to zebrafish embryos. Methods Zebrafish embryos were randomly divided into four groups: a solvent control group (dimethylsulphoxide) and three bromadiolone exposure groups (0.39, 0.78, and 1.18 mg·L⁻¹). The exposure period was from 4 h to 120 h post-fertilization. The number of spontaneous movement per minute was recorded at 24 h post-treatment. The locomotor ability of zebrafish larvae and the activity of acetylcholinesterase (AChE) were tested at 120 h post-treatment. The relative expression levels of neurodevelopment-related genes (elavl3, gap43, mbp, and syn2a) were measured by fluorescence quantitative PCR. Results Compared with the control group, the number of spontaneous movement per minute at 24 h decreased significantly in the 1.18 mg·L⁻¹ bromadiolone exposure group (P<0.05). Compared with the control group, the total distance travelled of the zebrafish larvae in the 0.78 and 1.18 mg·L⁻¹ bromadiolone exposure groups decreased by 60% and 69% respectively (P<0.05, P<0.01), and the total movement time decreased by 34% and 65% respectively (P<0.05, P<0.01). The AChE activity in the 1.18 mg·L⁻¹ bromadiolone exposure group increased by 36% when compared with the control group (P<0.05). The fluorescence quantitative PCR results showed that compared with the control group, the expression levels of neurodevelopment-related genes elavl3, syn2a, and mbp were significantly down-regulated by 66%, 69%, and 65% in the 1.18 mg·L⁻¹ bromadiolone exposure group respectively (P<0.01), the expression level of gap43 was up-regulated by 56% in the 0.78 mg·L⁻¹ bromadiolone exposure group (P<0.01) and down-regulated by 34% in the 1.18 mg·L⁻¹ bromadiolone exposure group (P<0.05). Conclusion Bromadiolone exposure could inhibit spontaneous movement and locomotive behavior, down-regulate the expression levels of neurodevelopment-related genes, hinder the release of neurotransmitters, and result in neurodevelopmental toxicity in the early-staged zebrafish.