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.

Objective:To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures.Methods:From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method.Results:A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure ( P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion:Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.

Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

Objective:To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures.Methods:From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method.Results:A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure ( P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion:Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.

The risks related to the essential performance were analyzed with considerations on the concept of the essential performance in GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance,and the determination process for the essential performance of medical electrical equipment was summarized.The essential performance of the example equipment was clarified with the semi-quantitative risk analysis,and the influences of the arrangement of the electromagnetic compatibility test on the determination of the essential performance were explored with the conducted immunity test and conventional test.References were provided for standard users to understand and determine the essential performance effectively.[Chinese Medical Equipment Journal,2024,45(11):72-76]

Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

Humans ; Immunologic Deficiency Syndromes/genetics*

Aim To study the hypnotic effect and safety of compound anshen essential oil. Methods Gas chromatograph-mass spectrometer (GC-MS) was used to analyze the main active components of compound anshen essential oil. The mouse model of insomnia was established by intraperitoneal injection of para-chloro-phenyl alanine ( PC PA ) , combined with pentobarbital sodium sleep experiment and EEG characteristic monitoring in rats to study the hypnotic effect and mechanism. The safety of compound anshen essential oil was evaluated by acute toxicity test, skin irritation/allergy test and 90-day repeated administration toxicity test. The clinical effect and safety were evaluated by using the sleep monitoring technology for micro-motion sensitive mattress. Results Four components, including Atractylone (34.61%), (+) -Limonene (17.80%) , Linalool (11.63%), and Ocimene (11.67%) , were detected as the main active components of compound anshen essential oil. Compound anshen essential oil in-halation administration for seven days could effectively reduce the autonomic activity of insomnia mice, shorten the sleep latency (P <0.05) , improve the sleep duration, increase of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and -γ-aminobutyric acid (GABA) in brain of mice with insomnia, and the medium dose group had better hypnotic effect. There was no death or adverse reaction in the safety evaluation test. The sleep balance index of 10 subjects with difficulty in falling a-sleep significantly increased (P <0.05), sleep latency was significantly shortened (P <0.05) , total sleep duration and sleep efficiency were improved, and no ad¬verse reactions were found after using the compound anshen essential oil for two days. Conclusions The compound anshen essential oil developed by the research team is safe and effective in relieving sleep disorders, which may be closely related to the co-regulation of the levels of neurotransmitters such as 5-HT and GABA by the four main active components.

Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.
Humans ; Triple Negative Breast Neoplasms/pathology* ; DNA Repair ; Mutation ; Combined Modality Therapy ; DNA Damage

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis