[摘 要] 目的：探讨环状RNA（circRNA）pumilio RNA结合家族成员1（PUM1）调节miR-337-3p/核磷蛋白1（NPM1）轴对子宫内膜癌（EC）Ishikawa细胞增殖、迁移、侵袭及凋亡的影响。方法：选用Ishikawa细胞，利用RNA干扰技术分别将为sh-circPUM1及其阴性对照（sh-NC）、anti-miR-337-3p及其阴性对照（anti-NC）质粒转染至Ishikawa细胞，实验分为对照组（未转染细胞）、sh-NC组、sh-circPUM1组、sh-circPUM1 + anti-NC组、sh-circPUM1 + anti-miR-337-3p组。qPCR法检测各组Ishikawa细胞中circPUM1、miR-337-3p、NPM1 mRNA的表达，CCK-8法、EdU染色法、Transwell小室实验和流式细胞术分别检测敲低circPUM1对Ishikawa细胞增殖、迁移和侵袭及凋亡的影响，WB法检测Ishikawa细胞中PCNA、NPM1、MMP-9、SNAIL、E-cadherin、BAX、C-caspase-3蛋白表达变化。双萤光素酶报告基因实验验证circPUM1与miR-337-3p、miR-337-3p与NPM1之间的靶向关系。结果：与sh-NC组和对照组相比，sh-circPUM1组Ishikawa细胞增殖能力、EdU阳性细胞率、迁移及侵袭细胞数、circPUM1、NPM1 mRNA及蛋白、PCNA、NPM1、MMP-9和SNAIL蛋白表达均显著降低（均P < 0.05），细胞凋亡率、miR-337-3p，以及细胞中E-cadherin、BAX和C-caspase-3蛋白表达均显著增加（均P < 0.05）；与sh-circPUM1组、sh-circPUM1 + anti-NC组相比，sh-circPUM1 + anti-miR-337-3p组细胞凋亡率、miR-337-3p、E-cadherin、BAX、C-caspase-3蛋白表达均显著降低（均P < 0.05），细胞增殖能力、EdU阳性细胞率、迁移及侵袭细胞数、NPM1 mRNA及蛋白、PCNA、NPM1、MMP-9和SNAIL蛋白表达均显著升高（均P < 0.05）。circPUM1可靶向负调控miR-337-3p、miR-337-3p可靶向负调控NPM1。结论：敲低circPUM1可以抑制Ishikawa细胞的恶性生物学行为，其机制可能是通过靶向miR-337-3p/NPM1轴实现的。

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

Objective: To analyze the association between sleep chronotype and suicidal psychological behaviors among middle school students, so as to provide a scientific basis for the prevention and control of middle school students suicide. Methods: In October 2021 and November 2022, a multistage cluster sampling method was used to conduct baseline and followup surveys in Shenyang, Zhengzhou, Nanchang, and Taiyuan cities in China, and a total of 6 656 middle and high school students were included as the research subjects. The Chisquare test was used to analyze the groups differences, and generalized estimating equation was used to analyze the associations between middle school students sleep chronotype and suicide ideation, suicide plan and suicide attempt, and the grade stratification was carried out. Results: Baseline detection of suicide ideation, suicide plan, and suicide attempt were 26.3%, 12.6%, and 5.3%, respectively, with followup rates of 21.0%, 10.0%, and 4.8% for each, and varied significantly by gender, academic stress, smoking or alcohol use, and anxiety or depressive symptoms among middle school students (χ2=11.93-880.20, P<0.05). After adjusting for gender, academic stress, physical activity, smoking, alcohol use, anxiety and depressive symptoms, generalized estimating equations showed that compared with the morning sleep chronotype, the OR(95%CI) for suicide ideation, suicide plan and suicide attempt were 1.61(1.36-1.89), 1.66(1.35-2.05) and 1.41(1.06-1.88) among evening chronotype students, and were higher among junior 1.78(1.39-2.27), 2.00(1.48-2.69) and senior middle school students 1.84(1.44-2.35), 1.67(1.20-2.33) (P<0.05). Conclusion There is a positive association between evening sleep chronotype and middle school students suicidal psychological behavior, and improving sleep chronotype may be one of the effective measures to prevent middle school students suicide.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Objective:To explore the relationship between the life satisfaction of family caregivers and the de-gree of disability of disabled elderly people in Xinjiang Uygur and Kazak nationality,and the role of family mem-bers'participation in the relationship.Methods:A total of 431 elderly people with disabilities at home and their fam-ily caregivers(247 without family members and 184 with family members)were selected from Xinjiang Uygur and Kazak ethnic groups,and the survey was conducted with the Activity of Daily Living Scale(ADL)and Life Satis-faction Index B(LSIB).Results:The LSIB scores in family caregivers were negatively correlated with the ADL scores in the disabled elderly(r=-0.19,P＜0.01),and the family members'participation in care was positively correlated with the LSIB scores of family caregivers(r=0.52,P＜0.01).Family members'participation in care could moderate the negative effect of the ADL scores in the disabled elderly on the LSIB scores in family caregivers(β=0.08,P＜0.05).Conclusion:The involvement of family members in care has a moderating effect on the life satisfaction of Uyghur and Kazak family caregivers and the degree of disability of disabled elderly people.

Iron is an indispensable nutritional element for human growth and development. It has a protective effect on cardiovascular. The changes and metabolism of iron can affect the physiological and pathological state of the body. Current research has confirmed that iron overload will promote the synthesis of cholesterol and increase lipid metabolism disorders. Lipid metabolic disorders in the body easily induce the occurrence and development of related metabolic diseases, and increase the hidden dangers of the outbreak of relevant risk factors. This article reviews iron and lipid metabolic and other metabolic diseases and natural products to prevent diseases through iron metabolic pathway, which aims to provide more powerful references for in-depth research on the mechanism of metabolic diseases and related diseases and target drug research and development.