OBJECTIVES: In recent years, the incidence and detection rate of pancreatic cystic lesions (PCLs) have increased significantly. Endoscopic ultrasound (EUS) plays an indispensable role in the diagnosis and differential diagnosis of PCLs. However, evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (FNB) remains limited. This study aims to compare the diagnostic yield, adequacy of tissue acquisition, and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice. METHODS: A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021. The diagnostic yield, tissue acquisition adequacy, and incidence of adverse events were compared between the 2 groups. RESULTS: A total of 90 patients with PCLs were included (52 in the FNA group and 38 in the FNB group). The diagnostic yield was similar between the FNA and FNB groups (94.2% vs 94.7%, P>0.05). The adequacy of tissue acquisition was 71.2% in the FNA group and 81.6% in the FNB group (P>0.05). No statistically significant difference was observed in the incidence of adverse events between the 2 groups (P>0.05). CONCLUSIONS Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs, with excellent safety profiles. Both methods are safe and effective diagnostic tools for evaluating PCLs.
Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects* ; Retrospective Studies ; Female ; Male ; Pancreatic Cyst/diagnostic imaging* ; Middle Aged ; Biopsy, Fine-Needle/adverse effects* ; Aged ; Pancreatic Neoplasms/diagnosis* ; Adult ; Endosonography/methods* ; Pancreas/pathology* ; Diagnosis, Differential

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Objective To evaluate the test-retest reliability of the ballistic push-up(BPU)test and establish predictive models for upper-limb strength and explosive power in young males.Methods A total of 71 male college students performed assessments of upper-limb bench press 1 repetition maximum(1RM)strength,bench press explosive power,and two BPU tests with a 48-hour interval.BPU test data were recorded using a three-dimensional(3D)force platform and motion capture system to calculate concentric metrics such as peak force(PF)and mean velocity(MV).The intraclass correlation coefficient(ICC)was used to examine the retest reliability of the BPU test.The Pearson correlation coefficient was used to evaluate the correlation of the BPU metrics with upper-limb strength and explosive power.Predictive models for upper-limb strength and explosive power were created using stepwise regression analysis.Results BPU metrics showed a good test-retest reliability(ICC=0.764-0.935).PF and MV,along with body weight(BW),were effective predictors of bench press 1RM in young males:bench press 1RM=0.129PF-16.772[R2=0.790,standard error of the estimate(SEE)=8.17 kg];bench press 1RM=1.511BW+87.15 MV-110.136(R2=0.767,SEE=8.60 kg).PF and BW were also predictors of bench press explosive power:bench press explosive power=2.755BW+0.287PF-17.351(R2=0.620,SEE=46.1 W).Conclusions The BPU test demonstrates a good test-retest reliability,and PF and MV from the BPU test can be used to predict upper-limb strength and explosive power in young males.

Objective·To investigate the genetic etiology of a rare and complex case clinically suspected to be methylmalonic acidemia(MMA),but with negative whole exome sequencing(WES)results,using a multi-omics sequencing approach.Methods·DNA and RNA samples were extracted from the peripheral blood of the proband and both parents.Targeted MMA-related gene Panel sequencing and WES were first performed.Subsequently,RNA sequencing(RNA-seq)and whole genome sequencing(WGS)were conducted to comprehensively analyze the child's genetic variants,their origins and potential inheritance patterns.Results·No pathogenic variants associated with the patient's phenotype were identified through the MMA Panel or standard WES analysis.Extended analysis of WES suggested the possibility of uniparental disomy(UPD)of chromosome 4.WGS revealed a homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the metabolism of cobalamin associated A(MMAA)gene.The variant was located in the 5'untranslated region(5'UTR),specifically at the second base downstream of the splice donor site of exon 1(reference sequence:NM_172250).In genomic coordinates(hg19),the variant was located at base 146540561 on chromosome 4(chr4:146540561).Sanger sequencing confirmed that the mother was heterozygous for this variant,while the father did not carry it.RNA-seq showed no detectable expression of the MMAA gene on chromosome 4 in the patient.This was further confirmed by reverse transcription real time quantitative PCR,indicating nearly absent mRNA expression,suggesting that the non-coding splice-site variant affected transcriptional expression.Conclusion·A homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the MMAA gene—outside the coverage of WES—is likely the pathogenic cause in this case,presumably resulting from maternal UPD of chromosome 4.