OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Abstract On 18 May 2021, the Center for Disease Control and Prevention (CDC) of X District in P City, Z Province received a co-investigation of a suspected case of intentional HIV transmission from the public security branch, and conducted epidemiological investigations on Zhao and Wang (both males). Wang was confirmed HIV-positive in 2019. Zhao had unprotected sexual encounters several times with Wang in March 2021 without being informed of Wang's HIV infection. Zhao developed fever, sore throat and other symptoms of acute infection phase on 28 March, and were confirmed HIV positive by the CDC of P City on 11 May. Zhao did not have sex with anyone else before or after having sex with Wang. In addition, Zhao had no history of surgery, blood transfusions, drug use or any other history of HIV exposure. Laboratory tests conducted by the CDC of Z Province showed that the HIV nucleic acid sequences between the samples of Zhao and Wang had a high degree of homology. Combined with the epidemiological investigation, laboratory testing and the evidence from the public security branch, it was concluded that Wang intentionally transmitted HIV to Zhao through unprotected anal sex without disclosing his HIV infection status.

Objective:To analyze the use of medicare antiviral drugs (ART) and related factors among HIV-infected people in Ningbo City.Methods:The retrospective data was collected related to infection and treatment of HIV-infected people in ART in Ningbo up to February 2023 through the National Infectious Disease Surveillance System. Binary logistic regression was used to analyze the factors related to medicare antiviral drug use in HIV-infected people. R 4.2.2 software was used for statistical analysis.Results:A total of 6 433 HIV-infected people with ART records were collected, among which 5 783 were in ART. The prevalence of medicare drugs use among people in ART was 24.8% (1 435/5 783, 95% CI: 23.7%-25.9%). Beilun District (8.7%, 43/497) and Fenghua District (5.7%, 14/247) had the lowest level in medicare drugs use. Among people in ART using medicare or out‐of‐pocket drugs, the prevalence of those who had at least one viral load test in the last year (84.9%, 1 352/1 593) was significantly lower than that of those using free drugs (91.4%, 3 829/4 190) ( χ2=52.50, P<0.001). The results of multivariate logistic analysis showed that the factors influencing medicare drug use included low educational level (junior high school and below: a OR=0.24, 95% CI:0.17-0.34), farmer or worker (farmer: a OR=0.60, 95% CI: 0.39-0.91; worker: a OR=0.42, 95% CI: 0.27-0.64), low monthly income (<3 000 Yuan: a OR=0.29, 95% CI: 0.18-0.45), the longer interval time between diagnosis and treatment (≥21 days: a OR=0.47, 95% CI: 0.30-0.74). Conclusions:Significant regional differences on the prevalence of medicare antiviral drugs use in HIV-infected people exist in Ningbo City. Follow-up management program of patients should be improved to strengthen patient compliance to mobilize medicare drug promotion. Meanwhile, publicity of medicare drugs should be strengthened for farmers or workers with low education level and patients with delayed treatment.

This paper aims to discuss the ideas and experience about the radiology residency training system of Canada with a presentation of its base accreditation standards for five aspects, competency goals for seven roles, four stages of training arrangement, and two types of final assessment questions. Although the Canada's radiology residency program differs from China's standardized resident and specialist training programs for radiology, there are still several points that are worth referencing, including emphasizing the training priority of competency goals, providing a specific basis for the stratification of training, offering clear guidance for the implementation of training content, and improving assessment methods to focus on competency goals. These points are of great value for improving the standardized radiology resident and specialist training programs in China, so as to provide a reference for the training of excellent radiologists in China.

Objective To analyze the effects of glucocorticoid stent implantation combined with nasal endoscopic surgery on nasal ventilation function and serum levels of eosinophil cationic protein(ECP),fibronectin(Fn)and aquaporin-1(AQP-1)in patients with chronic sinusitis with nasal polyp(CSwNP).Methods 60 patients with CSwNP from January 2022 to February 2023 were included in the study,and then they were divided into experimental group and control group,with 30 cases in each,using random number table method.The experimental group was treated with glucocorticoid stent implantation based on the original nasal endoscopic surgery,and the control group was treated with nasal endoscopic surgery,and both groups were treated until 12 weeks after surgery.The two groups of nasal symptoms,quality of life,nasal structure and ventilation function,serum levels of ECP,Fn,AQP-1,and adverse reactions were compared.Results Compared before the treatment,scores of nasal mucosal structure(Lund-Mackay scale),nasal symptom visual analogue scale(VAS)(including:nasal obstruction,runny nose,stuffy head,decreased sense of smell,nasal dryness/scab)and serum levels of ECP were decreased,distance from minimum nasal cross section to anterior nostril(DCAN)was shortened in two groups 12 weeks after treatment,and the experimental group was lower than the control group,the differences were statistically significant(P<0.05).Compared before the treatment,12 weeks after treatment,the nasal minimum cross-sectional area(NMCA),score of world health organization abbreviated quality of life(WHOQOL-100),nasal cavity volume(NCV),serum levels of Fn,AQP-1 were increased in two groups,and the experimental group was higher than the control group,the differences were statistically significant(P<0.05).During treatment,the incidence of adverse reactions was similar between the two groups(P>0.05).Conclusion Glucocorticoid stent implantation combined with nasal endoscopic surgery can control nasal symptoms in patients with CSwNP,improve nasal structure and ventilation function,regulate serum levels of ECP,Fn,AQP-1,and improve patients'quality of life.

Objective: To investigate the use of new types of drugs among HIV/AIDS patients in Ningbo City, Zhejiang Province, so as to provide insights into surveillance and interventions for use of new types of drugs among HIV/AIDS patients. Methods: The HIV/AIDS patients in Ningbo City were randomly sampled from the HIV/AIDS Prevention and Control Information System of Chinese Disease Prevention and Control Information System. Patients' demographics, use of new types of drugs and sexual behaviors were collected using questionnaire surveys. Patients' hair samples were collected, and new types of drugs were determined in hair using liquid chromatography-mass spectrometry (LC-MS). In addition, factors affecting the use of new types of drugs were identified using a multivariable logistic regression model. Results: A total of 254 HIV/AIDS patients were enrolled, including 214 men (84.25%), 31 cases aged under 25 years (12.20%), 66 cases aged 25 to 30 years (25.98%), and 157 cases aged 31 to 75 years (61.81%). There were 30 cases reported previous use of new drugs (11.81%), including 27 cases reported previous use of methamphetamine (90.00%). There were 48 cases tested positive of new types of drugs, with a positive rate of 18.90%, including 44 cases tested positive for methamphetamine (91.67%). Multivariable logistic regression analysis identified age (25 to 30 years, OR=6.926, 95%CI: 1.412-33.969), occupation (students/teachers/cadres/employees/retirees, OR=6.971, 95%CI: 2.123-22.889; housekeeping and housework servants/unemployed, OR=3.356, 95%CI: 1.289-8.739; business/public place servants, OR=2.447, 95%CI: 1.033-4.448) and syphilis infection during recent six months (OR=3.491, 95%CI: 1.664-7.326) as factors affecting the use of new types drugs among HIV/AIDS patients. Conclusions The use of new types of drugs exists in HIV/AIDS patients in Ningbo City. Age, occupation and syphilis infection were associated with the use of new types of drugs among HIV/AIDS patients.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

The clinical data of a case of Weave syndrome admitted in the Department of Endocrinology, Children′s Hospital of Nanjing Medical University in October 2018 were retrospectively analyzed.The patient was a 9 years and 2 months old girl, who was hospitalized because of " growing too fast for 9 years" . After birth, the child is found to grow fast and have mental retardation, slurred speech, a blurred vision, a long face, a protruding forehead, ocular hypertelorism, epicanthus, nasal bridge pit, finger pads on both hands and feet, uncoordinated gaits, and intoeingpigeon toes.A novel heterozygous c. 1720A>G (p.K574E) mutation was detected in the exon 15 of the EZH2 gene of the patient.This mutation has not been reported at home and overseas.Sanger sequencing revealed that the patient′s parents did not carry the mutation.The disease is an autosomal dominant genetic disorder, and the parents and sibling of the patient have no corresponding symptoms, so it is inferred that the mutation is spontaneous.Based on the peculiarity of the face, clinical manifestations and the results of molecular genetics, the child was diagnosed as Weaver syndrome.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC