Purpose: This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Materials and Methods: During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation. Results: CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months. Conclusion This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Objective:To evaluate the effect of toric collamer lens (TICL) rotation on myopia combined with astigmatism correction after V4c TICL implantation using standardized vector analysis.Methods:An observational case series study was performed.A total of 152 patients (268 eyes) who underwent V4c TICL implantation for the correction of myopia and myopic astigmatism were enrolled at Henan Eye Hospital from January to December 2021.The preoperative spherical diopter, cylindrical diopter, and spherical equivalent (SE) were -15.00 to -3.25 D, -5.00 to -0.50 D, -16.50 to -3.88 D, respectively.Postoperative TICL vault and axis were measured by anterior segment optical coherence tomography, and postoperative TICL rotation was calculated.Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), spherical diopter, cylindrical diopter, SE, and target astigmatism vector were recorded before and 1 month after surgery.The effectiveness index, safety index, surgically induced astigmatism vector (SIA), margin of error (ME), absolute value of the difference vector |DV|, correction index (CI), and achievement index (IS) were calculated based on the subjective refraction results 1 month after surgery and the cylindrical axis of the V4c TICL.Vector analysis parameters was compared among patients with different preoperative astigmatism, intraoperative TICL fixation, postoperative TICL rotation, and postoperative vault.The correlation between postoperative TICL rotation and TICL fixed angle deviation, postoperative vault, visual acuity and refraction, and vector analysis parameters were evaluated.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]).Written informed consent was obtained from each subject.Results:At 1 month postoperatively, the mean safety and efficacy indices were 1.27 and 1.29, respectively.There was no statistically significant difference between the predicted SE of (-0.11±0.13)D and the postoperative SE of (-0.07±0.52)D ( t=-0.994, P=0.321).UCVA, BCVA and cylinder diopter in the operative eyes were all improved after surgery compared to before surgery and the differences were statistically significant ( t=17.854, 5.446, -25.634; all P<0.001).The rotation of V4c TICL was 0° to 25°, with a mean of (5.41±4.35)°, which was positively correlated with the V4c TICL fixed angle deviation ( rs=0.461, P<0.001), negatively correlated with postoperative cylindrical diopter and positively correlated with postoperative UCVA, |DV| and SIA ( r=-0.360, 0.191, 0.205, 0.142; all P<0.05).Vector analysis between groups showed that vault, SIA and |DV| were higher and CI and IS were lower in low astigmatism group than in high astigmatism group ( Z=-3.017, -13.569, -2.793, -2.761, -4.779; all P<0.05).V4c TICL rotation and |DV| were lower in low fixation angle difference group than in high fixation angle difference group ( Z=-7.865, -2.080; both P<0.05).Preoperative cylindrical diopter, intraoperative V4c TICL fixed angle deviation, SIA and |DV| were lower in low rotation group than in high rotation group ( Z=-2.104, -4.578, -2.456, -2.090; all P<0.05).There were no statistically significant differences in the TICL rotation or in each vector between patients with different vault after the surgery (all P>0.05). Conclusions:V4c TICL implantation can achieve good results for the correction of myopia and myopic astigmatism.There is a slight difference between the fixation axis and the target axis of V4c TICL, which affects the rotation of V4c TICL and |DV|.Postoperative V4c TICL rotation is related to TICL fixed angle deviation, postoperative UCVA, SIA, |DV| and postoperative cylindrical diopter.Postoperative vault has no significant effect on TICL rotation and differences in each vector.

Objective:To evaluate the effect of toric collamer lens (TICL) rotation on myopia combined with astigmatism correction after V4c TICL implantation using standardized vector analysis.Methods:An observational case series study was performed.A total of 152 patients (268 eyes) who underwent V4c TICL implantation for the correction of myopia and myopic astigmatism were enrolled at Henan Eye Hospital from January to December 2021.The preoperative spherical diopter, cylindrical diopter, and spherical equivalent (SE) were -15.00 to -3.25 D, -5.00 to -0.50 D, -16.50 to -3.88 D, respectively.Postoperative TICL vault and axis were measured by anterior segment optical coherence tomography, and postoperative TICL rotation was calculated.Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), spherical diopter, cylindrical diopter, SE, and target astigmatism vector were recorded before and 1 month after surgery.The effectiveness index, safety index, surgically induced astigmatism vector (SIA), margin of error (ME), absolute value of the difference vector |DV|, correction index (CI), and achievement index (IS) were calculated based on the subjective refraction results 1 month after surgery and the cylindrical axis of the V4c TICL.Vector analysis parameters was compared among patients with different preoperative astigmatism, intraoperative TICL fixation, postoperative TICL rotation, and postoperative vault.The correlation between postoperative TICL rotation and TICL fixed angle deviation, postoperative vault, visual acuity and refraction, and vector analysis parameters were evaluated.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]).Written informed consent was obtained from each subject.Results:At 1 month postoperatively, the mean safety and efficacy indices were 1.27 and 1.29, respectively.There was no statistically significant difference between the predicted SE of (-0.11±0.13)D and the postoperative SE of (-0.07±0.52)D ( t=-0.994, P=0.321).UCVA, BCVA and cylinder diopter in the operative eyes were all improved after surgery compared to before surgery and the differences were statistically significant ( t=17.854, 5.446, -25.634; all P<0.001).The rotation of V4c TICL was 0° to 25°, with a mean of (5.41±4.35)°, which was positively correlated with the V4c TICL fixed angle deviation ( rs=0.461, P<0.001), negatively correlated with postoperative cylindrical diopter and positively correlated with postoperative UCVA, |DV| and SIA ( r=-0.360, 0.191, 0.205, 0.142; all P<0.05).Vector analysis between groups showed that vault, SIA and |DV| were higher and CI and IS were lower in low astigmatism group than in high astigmatism group ( Z=-3.017, -13.569, -2.793, -2.761, -4.779; all P<0.05).V4c TICL rotation and |DV| were lower in low fixation angle difference group than in high fixation angle difference group ( Z=-7.865, -2.080; both P<0.05).Preoperative cylindrical diopter, intraoperative V4c TICL fixed angle deviation, SIA and |DV| were lower in low rotation group than in high rotation group ( Z=-2.104, -4.578, -2.456, -2.090; all P<0.05).There were no statistically significant differences in the TICL rotation or in each vector between patients with different vault after the surgery (all P>0.05). Conclusions:V4c TICL implantation can achieve good results for the correction of myopia and myopic astigmatism.There is a slight difference between the fixation axis and the target axis of V4c TICL, which affects the rotation of V4c TICL and |DV|.Postoperative V4c TICL rotation is related to TICL fixed angle deviation, postoperative UCVA, SIA, |DV| and postoperative cylindrical diopter.Postoperative vault has no significant effect on TICL rotation and differences in each vector.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Objective:To investigate the high-risk factors for early postoperative recurrence in patients with colorectal cancer liver metastasis (CRLM).Methods:The clinical data of 156 CRLM patients who underwent hepatic metastasectomy at the Li Huili Hospital, Ningbo University from Jan 2015 to Dec 2021 was retrospectively analyzed.Results:Among 156 patients, the postoperative recurrence rate was 55.8% (87/156).There were significant differences ( P<0.05) in the primary tumor site, T stage, TBS score, preoperative concentrations of CEA, CA199 and CA125, the maximum diameter of metastatic tumors and the number of metastatic tumors between the group with recurrence in one year and the group without recurrence in one year. Multivariate analysis showed that preoperative CA125 concentration ( OR=1.021, P=0.020), CEA concentration ( OR=1.044, P=0.018), and tumor burden score ( OR=3.067, P=0.011) were high risk factors influencing early recurrence ( P<0.05). In the low TBS score group(≤4), among the 49 patients who underwent simultaneous resection, 13 suffered from recurrence within 1 year, with a recurrence rate of 26.5%. Meanwhile, among the 29 patients who underwent staged resection, 17 suffered from recurrence within 1 year, with a recurrence rate of 58.6% ( P<0.05). In the high TBS score group(>4), among the 51 patients who underwent simultaneous resection, 37 suffered from recurrence within 1 year, with a recurrence rate of 72.5%, while in the 27 patients who underwent staged resection, 20 suffered from recurrence within 1 year, with a recurrence rate of 74.1% ( P>0.05). Conclusions:Preoperative TBS score, preoperative CA125 concentration, and CEA concentration are high-risk factors for postoperative recurrence in patients with colorectal liver metastases, simultaneous resection in patients with a low TBS score can reduce the risk of recurrence within 1 year after surgery.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.