Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

ObjectiveTo evaluate the quality of clinical practice guidelines and expert consensus statements on knee osteoarthritis （KOA） based on the Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）， thus providing a new perspective for clinical selection as well as guideline development and updating. MethodsA systematic search was conducted for KOA-related guidelines and consensus statements published from November 1， 2019 to December 31， 2025. The databases and platforms searched included CNKI， VIP， Wanfang Data， PubMed， Web of Science， the National Institute for Health and Care Excellence （NICE）， SinoMed， Yimaitong， and relevant official websites. Two researchers independently screened the literature， and four researchers used AGREE Ⅱ to score the included documents and completed the quality appraisal after reaching a unified understanding. Subgroup analyses were further performed according to developing organization， document type， medical approach， funding status， and region of development， and longitudinal comparisons were conducted by year of publication. ResultsA total of 23 guidelines and consensus statements were included. The standardized scores of the six AGREE Ⅱ domains， from the highest to the lowest， were clarity of presentation ［（70.36±8.13）%］， scope and purpose ［（67.46 ± 11.44）%］， editorial independence ［（64.50±20.01）%］， rigor of development ［（62.24±15.26）%］， stakeholder involvement ［（55.73±10.29）%］， and applicability ［（53.89±13.17）%］. In terms of overall recommendation， 6 documents were rated as grade A and 17 as grade B. Stratified analyses showed that professional organizations scored higher than comprehensive organizations. The overall scores of traditional Chinese medicine/integrative medicine and Western medicine guidelines （or consensus statements） were similar. Guidelines scored higher than consensus statements. The overall scores were similar between documents with reported funding and those without reported funding. International guidelines scored higher than domestic guidelines. Longitudinal comparisons showed that the largest number of documents was published in 2021. The overall scores were higher in 2021—2022， and some domain scores declined in 2023—2024. Overall， the quality of recent guidelines and consensus statements for KOA showed slight fluctuations， without a clear linear trend. ConclusionThe included guidelines and consensus statements for KOA can generally serve as references for clinical practice. However， the quality across domains remains uneven， and stakeholder involvement and applicability are still weak domains. Future guideline development and updating should further improve methodological standardization and transparency in reporting.

Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03％of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24％(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.

Objective:To examine the relationship between perceived stress and clinical practice maladjust-ment,as well as the mediating roles of executive function and depressive symptoms in the relationship among intern nurses.Methods:A total of 624 nursing interns were recruited and followed up during this eight-month longitudinal study.Baseline data(Tl)were collectedon the day of internship orientation(July 2022)with the Perceived Stress Scale(PSS),Geurten Executive Function Questionnaire(G-QEF)and Patient Health Questionnaire Depression Module(PHQ-9).Follow-up data(T2)were collected shortly before the end of the internship(March 2023)with the PSS,G-QEF,PHQ-9,and Nursing Students Clinical Internship Maladjustment Scale(NSCPMS).The chain me-diation effect of executive function and depressive symptoms in the relationship between perceived stress and clini-cal practice maladjustment was analyzed.Results:The PSS scores at T1 significantly predicted the NSCPMS scores at T2(β=-1.00,P＜0.001).Executive function and depressive symptosm jointly mediated the relationship be-tween perceived stress and clinical practice maladjustment,with a mediation effect value of-0.01(95％CI=-0.026--0.004).Additionally,depressive symptoms alone significantly mediated the relationship between per-ceived stress at T1 and clinical practice maladjustment at T2,with a mediation effect value of-0.06(95％CI=-0.101--0.017).Conclusion:Perceived stress at the beginning of the internships may negatively impact long-term clinical adjustment among nursing interns,potentially through impaired executive function and depressive symptoms.This finding suggests that early prevention measures and interventions to reduce stress at the start of in-ternships are needed to help interns better adapt to clinical practice.

Objective:To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. Methods:A female IP patient with a heterozygous IKBKG c. 1167dup variant but without family genetic data who sought genetic counseling at Women and Children′s Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094). Results:In total seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38 + 6 weeks of gestation. Conclusion:For IP patients with de novo mutation or without family samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.

Objective:To establish a scientific,systematic,and objective indicator system for the characteristic price variables of Traditional Chinese Patent Medicines(TCPM),providing a reference framework for the pricing mechanism of TCPM.Methods:The brainstorming method was initially used to screen related variable indicators.The Nominal Group Technique(NGT)and Delphi methods were applied to gather expert opinions,and SPSS 28.0 was employed for data statistical analysis.It led to the development of a TCPM characteristic price variable indicator system consisting of 6 dimensions,14 characteristic variables and 26 measurement indicators.Results:The authority coefficient of the experts exceeded 0.7,indicating the representativeness of the results.Expert opinions were generally concentrated.Based on the collected opinions and statistical analysis,the scope of selected TCPM characteristic price variables was preliminarily established.Conclusion:The TCPM characteristic price variable indicator system was initially developed.However,due to the complexity of the pricing mechanism and divergent expert opinions,further qualitative and quantitative research methods,along with a dynamic adjustment mechanism,are needed to verify and refine the system.

Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03％of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24％(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.

Aim To investigate the relationship between sleep deprivation and vascular aging,as well as the un-derlying mechanisms.Methods Male Sprague-Dawley rats were divided into control group,senescence group,sleep deprivation group,and sleep deprivation+senescence group,with 6 rats in each group.The modified level table method deprived rats of sleep duration.Senescence-associated β-galactosidase(SA-β-Gal)staining was used to detect the senes-cence status of rat vascular tissue.The mRNA and protein expression of tumor suppressor protein p53,silent information regulator 1(SIRT1)and clock gene cryptochrome 1(CRY1)was detected by real-time fluorescence quantification PCR(RT-qPCR),Western blot and immunohistochemistry.Results Compared with the control group,the intensity of SA-β-Gal staining was increased in the vascular tissues of the senescence group rats,the expression level of p53 was elevat-ed,the expression level of SIRT1 was decreased.Similar changes were observed in the sleep deprivation group and the sleep deprivation+senescence group,including intensified SA-β-Gal staining,elevated p53 levels,and reduced SIRT1 lev-els in vascular tissues.Additionally,compared with the control group,the sleep deprivation group showed reduced CRY1 levels in vascular tissues,while only CRY1 mRNA levels were reduced in the sleep deprivation+senescence group.Fur-thermore,compared with the senescence group,the sleep deprivation+senescence group exhibited intensified SA-β-Gal staining,increased p53 level,decreased SIRT1 level,and reduced CRY1 mRNA level in vascular tissues.Conclusion Sleep deprivation may promote the expression of vascular aging-related factors,potentially through the inhibition of CRY1 expression in vascular tissues.

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

Objective: To explore effects and maintenance of school based sexual abuse prevention programs for minors, so as to provide scientific evidences for optimizing intervention design and policy making. Methods: Six Chinese and English databases were searched, including CNKI, Wanfang Database, Medline (via PubMed), Embase, Cochrane Library and Web of Science, with the time frame set from database inception to December 31, 2024. Studies on school based sexual abuse prevention programs for minors were selected, and data on knowledge, attitudes and skills related to sexual abuse prevention were extracted. Meta analysis was performed using Stata 17. Results: A total of 26 studies were included. The Meta analysis results showed that school based sexual abuse prevention programs improved participants knowledge ( SMD=1.24, 95%CI =0.96-1.52), attitudes ( SMD=0.62, 95%CI =0.19-1.04) and skills ( SMD=0.66, 95%CI =0.50-0.83) (all P <0.01). During the overall follow up, the maintenance rates for knowledge, attitudes, and skills were 0.97(95% CI =0.95-1.00), 0.99(95% CI =0.95-1.04) and 1.01(95% CI =0.99-1.04), respectively, with no statistically significant differences (all P >0.05). However, knowledge retention declined significantly when follow up exceeded three months ( R=0.91, 95%CI=0.83-0.99, P <0.01), while skills retention ( R=0.94, 95%CI=0.87-1.02, P = 0.23) remained higher than knowledge and attitudes ( R=0.98, 95%CI=0.96-1.00, P =0.13), demonstrating stronger long term effects. Conclusion School based sexual abuse prevention programs are effective in enhancing participants knowledge, attitudes and skills, but the intervention effects diminish over time, particularly in knowledge retention.