BACKGROUND:The onset of COVID-19 and subsequent restrictive measures have impacted various infectious diseases, including hepatitis B virus (HBV). This study explored the epidemiological characteristics of HBV infection in Chinese adults before, during the pandemic, and after the easing of restrictive measures. METHODS:This population-based cohort study used the data from 23,316 adult patients in the southwest of China who had HBV DNA tests from 1 January 2018 to 31 December 2023. HBV DNA was detected in patient serum using real-time fluorescent quantitative PCR. The positive rate of HBV detection was adjusted by age groups, sex, patient types, and seasons, stratified by the stages of the COVID-19 pandemic. RESULTS:Our analysis revealed significant variations in HBV DNA test positivity rates, primarily influenced by age and the pandemic stages. Positivity rates were highest in the 18-25 age group at 0.50 and decreased with advancing age. Males under 35 were at higher risk. Inpatients had the highest positivity rate at 0.42, with seasonal fluctuations peaking in winter. The pandemic stages significantly affected positivity rates, especially in the 36-45 and 56-65 age groups. CONCLUSION:The findings highlight a complex interplay between pandemic conditions and observed positivity rates. The increase likely stemmed from multiple factors, including shifted testing focus, altered healthcare-seeking behavior, and potential viral reactivation. The COVID-19 response offers insights for optimizing future viral hepatitis control strategies during public health emergencies. Future research should expand demographic and geographic scope and investigate behavioral/social determinants to elucidate underlying mechanisms and guide targeted interventions.

The application of nonconventional nonaromatic luminophores-based hydrogels (NLHs) in bioanalysis is severely limited due to their luminescence in concentrated solution or solid state. Herein, a nonconventional NLH (B-Au@PDMAA) with high signal-to-noise ratio and stability in dilute solutions is designed by enhancing nonaromatic luminophores intermolecular aggregation through bovine serum albumin-gold nanoclusters (B-Au) confined space interaction. Importantly, the established NLHs could be rapidly polymerized in situ on magnetic beads (MB) surface in dilute solutions, and the fluorescence intensity after polymerization is 5.63-fold higher than that of direct polymerization. Moreover, proposed B-Au@PDMAA@MB constructed homogeneous immunoassay platform is demonstrated to be highly sensitive for detecting hepatitis B surface antigen with a sensitivity of 3.39 ng mL-1, which is 28.6-fold lower than that of B-Au@PDMAA based immunoassay and comparable to the sensitivity of the chemiluminescence immunoassay. This work presents a new strategy for the synthesis of NLHs with high brightness and stability in dilute solutions, and opens new avenues for the construction of novel homogeneous immunoassay platforms. Bovine serum albumin-gold nanoclusters (B-Au) can be used to improve the sensitivity and stability of nonconventional nonaromatic luminophores hydrogels-based immunoassay by two aspects, namely, 1) etched B-Au enhanced the blue, yellow, and red fluorescence, and 2) confined space interaction originated from poly-N,N-dimethylacrylamide/BSA hydrogen bond interaction, BSA hydrophobic domain-limiting effect, and gold atom-based coordination interaction.image

目的 分析糖尿病患者发生血流感染的病原学特征及死亡危险因素,以寻找可能改善患者预后的诊疗方案.方法 回顾性分析2017-2021年绵阳市第三人民医院收治的糖尿病血流感染患者的临床及实验室检查资料,使用WHONET 5.6软件统计分析病原菌的分布及药敏结果.将患者按照感染后30 d疾病转归分为生存组、死亡组,分析患者发生全因死亡的危险因素.结果 共334例糖尿病血流感染患者被纳入研究,分离出非重复病原菌347株,以大肠埃希菌(143株,41.2％)、肺炎克雷伯菌(83株,23.9％)、金黄色葡萄球菌(22株,6.3％)最为常见;其中泌尿道感染的病原菌以大肠埃希菌、肺炎克雷伯菌多见,呼吸道感染的病原菌主要是肺炎克雷伯菌、大肠埃希菌、金黄色葡萄球菌,90％以上的肝脓肿源性血流感染由肺炎克雷伯菌引起.不同类型血流感染的病原菌构成存在差异,大肠埃希菌、肺炎克雷伯菌等肠杆菌目细菌在社区获得性感染中分离率更高,而铜绿假单胞菌、鲍曼不动杆菌、念珠菌更常见于医院获得性血流感染患者.大肠埃希菌对氨苄西林、哌拉西林等的耐药率均高于50％,对哌拉西林-他唑巴坦、亚胺培南、米诺环素等药物的耐药率低于10％,医院获得性感染分离株对头孢菌素类、氟喹诺酮类、β内酰胺类及其酶抑制剂复方制剂等抗菌药物的耐药率高于社区获得性感染.肺炎克雷伯菌对常用抗菌药物的耐药率均低于30％,医院获得性感染分离株对头孢菌素类、碳青霉烯类、氨基糖苷类、氟喹诺酮类等抗菌药物的耐药率高于社区获得性感染.病程中使用非敏感抗生素经验性治疗、未使用胰岛素控制血糖、发生急性并发症、Pitt菌血症评分升高是患者的全因死亡危险因素,比值比(OR)分别为8.261、2.719、5.263、1.918.结论 糖尿病患者血流感染的致病菌以大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌最为常见,病原菌分布与患者的感染部位、感染类型相关,其中分离自医院获得性血流感染的大肠埃希菌、肺炎克雷伯菌耐药形势较为严峻.糖尿病患者血流感染的全因死亡危险因素有感染初期使用非敏感抗菌药物经验性治疗、未使用胰岛素控制血糖、出现急性并发症和病程中Pitt菌血症评分升高.

Background For people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed. Methods In order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo. Results This newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94. Conclusions The in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy.

Advanced differentiated thyroid cancer cells are subjected to extreme nutritional starvation which contributes to develop resistance to treatments; however, the underlying mechanism remains unclear. Cells were subjected to serum deprivation by culture in medium containing 0.5% fetal bovine serum. A CCK8 assay, cell death Detection ELISAPLUS kit, and PI staining were conducted to determine cell viability, cell apoptosis, and cell cycle, respectively. NADPH oxidase 4 (NOX4) knockdown–stable cell lines were generated by lentivirus-mediated shRNA knockdown in BCPAP cells and TPC-1 cells. Etoposide and doxorubicin, two chemotherapeutic drugs, as well as lenvatinib were utilized to determine the effect of NOX4 on drug resistance. Lenvatinib-resistant BCPAP cells (LRBCs) were established to confirm this effect. The underlining mechanisms of NOX4 under starvation were explored using western blot. Finally, GLX351322, an inhibitor targeting NOX4, was used to inhibit NOX4-derived ROS in vitro and detect its effect on drug resistance of tumor cells in vivo. NOX4 is overexpressed under serum deprivation in BCPAP or TPC-1 cells. NOX4 knockdown impairs cell viability, increases cell apoptosis, extends G1 phase during cell cycle and modulates the level of energy-associated metabolites in starved cells. When the starved cells or LRBCs are treated with chemotherapeutic drugs or Lenvatinib, NOX4 knockdown inhibits cell viability and aggravates cell apoptosis depending on NOX4-derived ROS production. Mechanistically, starvation activates TGFβ1/SMAD3 signal, which mediates NOX4 upregulation. The upregulated NOX4 then triggers ERKs and PI3K/AKT pathway to influence cell apoptosis. GLX351322, a NOX4-derived ROS inhibitor, has an inhibitory effect on cell growth in vitro and the growth of BCPAP-derived even LRBCs-derived xenografts in vivo. These findings highlight NOX4 and NOX4-derived ROS as a potential therapeutic target in resistance to PTC.

目的 分析川西北地区影响念珠菌血症患者预后的相关危险因素,并总结其临床特征.方法 选取2019年1月至2020年12月期间川西北地区住院接受治疗的120例念珠菌血症患者,对其临床资料进行回顾性分析,统计其病原菌种类及耐药情况,并分析影响患者预后的有关危险因素.结果 本研究120例患者中治疗后生存80例,死亡40例,真菌血培养共分离出念珠菌120株,其中热带念珠菌25株,对伊曲康唑、氟康唑的耐药率偏高;季也蒙念珠菌2株,对伊曲康唑、氟康唑、两性霉素B、氟胞嘧啶四种抗真菌药物均具有较高的灵敏度.光滑念珠菌,近平滑念珠菌、白色念珠菌、克柔念珠菌分别为13株、30株、45株、5株,对这4种抗真菌均具有一定的耐药性.多因素回归分析结果显示,器官衰竭、脓毒性休克是影响该疾病患者预后的主要危险因素(P<0.05).结论 念珠菌菌血症患者致病菌种类较多,且对部分抗真菌药物具有耐药性,器官衰竭和脓毒性休克可增加患者的死亡风险.

Accumulated evidence revealed that numerous long noncoding RNAs (lncRNAs) have been found to be involved in the development and progression of hepatocellular carcinoma (HCC). LINC00628, a member of lncRNAs, has been reported to act as a tumor suppressor in gastric cancer and breast cancer. However, its potential role in HCC still remains unknown. Herein, we characterized the function of LINC00628 in HCC. Our investigation has revealed that LINC00628 were dramatically decreased in HCC tissues and cells, and inhibited the migration and invasion of HCC cells in vitro and in vivo. Moreover, LINC00628 exerted its tumor suppressive function by repressing the vascular endothelial growth factor A (VEGFA) promoter activity. A highly conserved region element in LINC00628 was identified by a cross-species comparative analysis, which is required for LINC00628 exerted its function. Dual-luciferase reporter assay showed that the conserved sequence mediated the interaction with a specific region of VEGFA promoter, resulting in a decrease of VEGFA expression. In conclusion, our results demonstrated that LINC00628 could function as a tumor suppressor in HCC via its conserved sequence elements interacting with a particular region of VEGFA promoter, suggesting that LINC00628 may serve as a novel promising target for diagnosis and therapy in HCC.

Background: Emerging studies demonstrate that long noncoding RNAs (lncRNAs) play crucial roles in hepato-carcinogenesis through various mechanisms. LncRNA CCAT2 was a newly discovered lncRNA and amplified in several cancers. However, the mechanisms involved in function of CCAT2 in hepatocellular carcinoma (HCC) remain to be explored. Methods: CCAT2 expressions in HCC tissues and cell lines were measured by RT-qPCR. MTS assay, colony formation assay, wound-healing assay and transwell assay were used to explore the biological functions of CCAT2 on HCC cells proliferation and metastasis. Experiments in vivo were carried out to confirm these effects. The underlying mechanisms were analyzed by western blot and dual-luciferase reporter assay. Results: In this study, we found that CCAT2 were significantly elevated in HCC tissues and cell lines, and it promoted HCC cells proliferation and metastasis both in vitro and in vivo. Additionally, we identified that NDRG1 was a downstream target of CCAT2. Meanwhile, depletion of CCAT2 inhibited cellular proliferation and metastasis behaviors induced by NDRG1- overexpression. Analysis of mechanism underlying these effects revealed that CCAT2 increased the expression of NDRG1 by enhancing its promoter activity. Furthermore, the active region between CCAT2 and NDRG1 promoter was confirmed by dual-luciferase reporter assay. Conclusions: All these observations demonstrate that CCAT2 acts as an oncogene by up-regulating NDRG1, which may have the potential to be used as a promising prognostic biomarker and therapeutic target for HCC.

Thyroid cancer is one of the most common endocrine cancers with rapidly increasing incidence in recent dec-ades. Although the majority of patients with thyroid cancer have a good prognosis, there is still a risk that some cases may develop into more aggressive and lethal thyroid cancers. Long noncoding RNAs (lncRNAs) have recently been demonstrated to participate in cancer progression. However, their role and molecular mechanism in thyroid cancer remain unclear. In this review, we summarize the latest findings regarding the functions and mechanism of lncRNAs in thyroid cancer, and discuss their potential clinical significance in diagnosis, prognostic biomarkers and therapeutic targets of thyroid cancer.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in a variety of diseases, including many tumors, such as hepatocellular carcinoma (HCC). However, the function and mechanisms responsible for these molecules in HCC are not thoroughly understood. In our previous study, we found that LINC00052 was acted as a tumor suppressor in HCC. In this study, we performed transcription microarray analysis to investigate the target gene of LINC00052, and found that knockdown of LINC00052 significantly increased the expression of SRY-related HMG-box gene 9 (SOX9), which plays an oncogenic role in HCC. Moreover, luciferase reporter assay revealed that LINC00052 promoted miR-101-3p expression by enhancing its promoter activity. In addition, online database analysis tools and luciferase assays showed that miR-101-3p could target SOX9. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that miR-101-3p was downregulated in HCC tissues and HCC cell lines. And we found a positive relationship between LINC00052 and miR-101-3p, and a negative relationship between miR-101-3p and SOX9 in HCC tissues. Besides, miR-101-3p was involved in LINC00052 inhibits HCC cells proliferation and metastasis. At the molecular level, LINC00052 downgulated SOX9 to inhibit HCC cells proliferation and metastasis by interacting with miR-101-3p. It might be a potential application for HCC therapy.

Background Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC). Methods In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575. Results We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC. Conclusions Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC.

目的 探讨降钙素原(PCT)和超敏C反应蛋白(hs-CRP)定量检测对精神科患者血流感染的诊断价值.方法 回顾性分析2015年1月至2016年6月本院临床确诊的80例细菌血流感染及100例非血流感染精神科患者的PCT、hs-CRP值,比较两组间PCT和hs-CRP浓度的差异.结果 血流感染患者PCT为14.88(3.18~25.02)ng/ml,hs-CRP为84.21(50.01~130.06)mg/L;非血流感染组PCT为0.18(0.09~2.09)ng/ml,hs-CRP为32.85(17.80~39.04)mg/L.血流感染组和非血流感染组的PCT、hs-CRP比较有统计学意义(P<0.05).PCT与hs-CRP诊断血流感染ROC曲线下面积分别为0.951、0.738.结论 PCT、hs-CRP均可用于血流感染的鉴别诊断,PCT诊断价值更高.

Objective To investigate the clinical distribution and drug resistance of carbapenem resistant Acinetobacter baumannii in order to provide reference for clinical rational use of antibiotics and prevention and control of nosocomial infection. Method From January 2013 to December 2015,the distribution and drug sensitive data of clinical isolates of carbapenem resistant Acinetobacter baumannii were retrospectively analyzed. Results A total of 706 strains of Acinetobacter baumannii were isolated. Among them,523 strains of carbapenem resistant Acinetobacter Bauman,and the isolation rate was about 74. 1%. The main source of specimenwas sputum ( 81. 8%) . They were mainly distributed in the intensive care unit ( 40. 3%) and respiratory medicine (22. 2%) . Drug resistance rate showed an overall upward trend. The resistant rate of Cefoperazone / Shubatan was the lowest( <38. 0%) . The second was minocycline( <43. 0%) ,highly resistant to other antimicrobial agents. In addition to compound sulfame-thoxazole,the resistance rate of carbapenem resistant Acinetobacter baumannii was significantly higher than that of non carbapenem resistant Acinetobacter baumannii(P<0. 01). Conclusion We should strengthen the monitoring of drug resistance of carbapenem resistant Acinetobacter baumannii,carefully use carbapenem antibiotics,and take effective measures to prevent and control it.

目的:探讨ROC曲线评价妊娠中期糖化血红蛋白(HbA1c)对诊断妊娠糖尿病的价值.方法:选择75例已知孕中期筛查为妊娠糖尿病的孕妇和75例正常糖耐量的孕中期孕妇,同时测定糖化血红蛋白,利用ROC曲线评估其诊断妊娠糖尿病的价值,根据Youden指数确定诊断cut-off值.结果:以OGTT实验为诊断的金标准,HbA1c的ROC曲线下的面积(AUC)为0.786,cut-off值为5.05％.结论:HbA1c cut-off值为5.05％,对妊娠中期妇女妊娠糖尿病诊断有较好的应用价值.

目的：了解我院流感嗜血杆菌检出状况与耐药情况，指导临床合理用药。方法对123株流感嗜血杆菌利用V+X、V、X因子需求试验进行初步鉴定，再用VITEK 2 compact全自动细菌鉴定仪进行复核鉴定。药物敏感性试验采用纸片扩散法，β-内酰胺酶采用头孢硝噻吩纸片检测，数据采用whonet5.4软件进行分析和统计。结果离出的123株流感嗜血杆菌对复方新诺明耐药率最高71.6%，氨苄西林次之43.8%，而对头孢曲松，头孢噻肟，环丙沙星，左旋氧氟沙星，莫西沙星敏感率均在95%以上，β-内酰胺酶检出率37.8%。结论感嗜血杆菌对大多数抗菌药物仍保持良好的抗菌活性，但对复方新诺明的耐药率较高，临床医师应重视常用抗菌药物的耐药率，合理使用抗菌药物。

目的：分析我院2014年血培养分离出的病原菌分布及耐药情况，为临床合理用药提供参考依据。方法对2724份患者血培养标本经Bactec 9120全自动血培养仪培养，VITEK-2 Compact微生物分析系统进行菌株鉴定，采用K-B法进行体外药敏试验，应用WHONET 5.6软件分析药敏结果。结果血培养标本分离出病原菌共324株，其中革兰阴性杆菌171株(52.78%)，革兰阳性球菌147株(45.37%)，真菌6株(1.85%)。检出率位于前5位的分离菌依次为大肠埃希菌(98株，30.25%)、表皮葡萄球菌(38株，11.73%)，肺炎克雷伯菌(28株，8.64%)、人葡萄球菌(25株，7.72%)，金黄色葡萄球菌(18株，5.56%)。药敏试验显示，金黄色葡萄球菌、表皮葡萄球菌、人葡萄球菌对万古霉素、利奈唑胺、替考拉宁敏感率均为100%。对大肠埃希菌和肺炎克雷伯菌，碳青霉烯类、含酶抑制剂的β-内酰胺类和阿米卡星保持较高的敏感性。结论血培养病原菌种类较多，以革兰阴性杆菌为主，耐药性差异较大，应及时监测血培养病原菌菌种及耐药性的变化，防止滥用抗菌药物，减少不合理的经验性治疗。

目的：了解我院肠球菌在临床标本中的分布及其耐药情况，为临床合理治疗肠球菌感染提供依据。方法对我院2011年1月至2013年6月各类临床标本进行分离培养，菌株鉴定采用全自动细菌鉴定仪，药物敏感性试验采用纸片扩散法，数据采用WHONET5.4软件进行分析和统计。结果从各种临床标本中共分离到肠球菌230株，其中粪肠球菌100株，屎肠球菌107株。标本主要来源于尿液(59.13%)、胆汁(17.39%)和血液(10.00%)。从粪肠球菌和屎肠球菌药物敏感试验对比来看，屎肠球菌的耐药性强于粪肠球菌。在受试抗菌药物中，肠球菌对替考拉宁的耐药率最低，其次为利奈唑胺和万古霉素。结论替考拉宁、利奈唑胺和万古霉素是对肠球菌抑制率最高的药物，但临床已检出耐万古霉素和利奈唑胺的肠球菌。由于肠球菌种的差异其耐药性有较大差异，临床应根据药敏试验结果合理选择抗菌药物。

Objective To investigate the distribution and antibiotic resistance of Klebsiella pneumoniae(KPN) isolated from our hospital and offer suggestions for clinic.Methods The specimens submitted from the hospitalized patients were isolated and cultured from January to December 2012,the bacterial identification were performed by adopting the automatic microorganism analyzing system.The antibiotic susceptibilities to 25 kinds of antibiotics were tested by K-B method and analyzed by Whonet software.Double disk synergy test was adopted in the strains with extended ESBLs,the distribution and the use of antibiotics were analyzed.Results There were 294 strains of K.pneumoniae isolated among which there were 62 ESBLs producing strains with the detection rate of 21.1% in the 294 KPN.The strains were mainly isolated from the sputum,accounting for 67.35%.The isolates mainly distributed in ICU(19.05%).The drug resistance rate of ESBLs producing strains was significantly higher than that of nonESBLs-producing strains(P<0.01).Conclusion KPN isolates,ESBLs producing strains in particularly,show resistance to the antibiotics in the investigation.The drugs should be chosen reasonably according to their antibiotic susceptibility results so as to effectively control the drug resistant strains.