ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

AIM: To evaluate the accuracy of the formulas, including Haigis, SRK/T, Holladay 1, and Holladay 2, in predicting the diopter of the intraocular lens implanted in high myopia cataract patients.METHODS: Prospective study. A total of 168 cases(168 eyes)of age-related cataract with an axial length(AL)≥26 mm who were treated in our hospital from August 2017 to November 2021 were selected. According to the preoperative AL measured by IOL Master 700, the patients were divided into five groups, including 37 cases(37 eyes)in group A with 26 mm≤AL<27 mm, 34 cases(34 eyes)in group B with 27 mm≤AL<28 mm, 42 cases(42 eyes)in group C with 28 mm≤AL<29 mm, 28 cases(28 eyes)in group D with 29 mm≤AL<30 mm, and 27 patients(27 eyes)in group E with AL ≥ 30 mm. Subjective refraction was performed at 3 mo postoperatively, and the mean numerical error(MNE)and mean absolute error(MAE)of each formula for predicting diopters were calculated.RESULTS: The MNE and MAE of the Haigis and Holladay 2 formulas were relatively less in each group, and MNE and MAE did not significantly increase with the growth of the axial length. However, the MAE and MNE of the SRK/T and Holladay 1 formulas significantly increased with the growth of the axial length, with the MNE and MAE of the Holladay 1 formula increasing more significantly in groups C, D, and E.CONCLUSION: For patients with age-related cataract, with an axial length of ≥26 mm, the accuracy of predicting the diopter of the intraocular lens using the Haigis and Holladay 2 formulas were higher.

Background and purpose:Long noncoding RNA(lncRNA)can regulate gene transcription,mRNA shear,stabilization and translation,and it is an important regulatory factor in a variety of biological processes.This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma(OSCC)and its effect on the malignant biological behavior of OSCC.Methods:The expression of FLJ30679 in head and neck squamous cell carcinoma(HNSCC)tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis.The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays.FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group(SS-FLJ30679),and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group(FLJ30679).The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition(EMT)-related genes in OSCC cells.The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase(AKT)pathway were detected by Western blot.Results:Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues(P＜0.01).HNSCC patients with higher FLJ30679 expression had lower overall survival(P＜0.01).The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells,and was predominantly localized in the nucleus.The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group(P＜0.01).OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group(P＜0.001).RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin(P＜0.01)and downregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.01).FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin(P＜0.01)and upregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.05).Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT)(P＜0.001),and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT(P＜0.01).Conclusion:The expression of FLJ30679 was increased in OSCC tissues and cells.It promoted the proliferation and migration ability of OSCC cells,which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway.

AIM:This study aimed to investigate the expression and localization of ALOX12P2 in oral squa-mous cell carcinoma(OSCC),as well as its effects on cell viability,migration,and invasion.METHODS:The expres-sion of ALOX12P2 in head and neck squamous cell carcinoma(HNSCC)tissues and its correlation with clinicopathologi-cal features were analyzed using the UALCAN database(University of Alabama at Birmingham Cancer Data Analysis Por-tal).Additionally,the expression of ALOX12P2 in OSCC and its impact on survival prognosis were evaluated through the GDC and UCSC Xena databases.The expression levels of ALOX12P2 in OSCC cell lines were assessed via quantitative re-al-time PCR(RT-qPCR).The subcellular localization of ALOX12P2 was determined using nucleoplasmic RNA isola-tion.CAL-27 cells were used to establish an ALOX12P2 knockdown group(SS-ALOX12P2)and a control group(SS-NC).HN30 cells were employed to form an ALOX12P2 overexpression group(ALOX12P2)and a control group(vector).The effects of altered ALOX12P2 expression on the epithelial-mesenchymal transition(EMT)-related gene E-cadherin and the PI3K/AKT signaling pathway were assessed through Western blot analysis.RESULTS:ALOX12P2 expression was significantly higher in HNSCC and OSCC tissues compared to normal tissues,with its expression correlating with poor prog-nosis.RT-qPCR analysis indicated that the relative expression of ALOX12P2 in OSCC cells was comparable to that in nor-mal cells(P<0.05).RNA nucleoplasmic isolation confirmed that ALOX12P2 localized in the nucleus.In comparison to the SS-NC group,the SS-ALOX12P2 group exhibited a marked reduction in ALOX12P2 expression(P<0.01),alongside significant decreases in cell viability,migration,and invasion(P<0.01).Conversely,the ALOX12P2 group showed sub-stantially higher relative expression compared to the vector group(P<0.01),with enhanced cell viability,migration,and invasion abilities(P<0.01).Western blot analysis demonstrated that ALOX12P2 knockdown resulted in upregulation of E-cadherin and downregulation of N-cadherin and Vimentin(P<0.01),while overexpression of ALOX12P2 yielded the opposite effects(P<0.01).Knockdown of ALOX12P2 led to decreased protein expression of p-PI3K and p-AKT(P<0.01),whereas overexpression increased these protein levels(P<0.01).CONCLUSION:ALOX12P2 is highly ex-pressed in OSCC and promotes cell viability,migration,and invasion.This effect may be linked to the activation of the PI3K/AKT signaling pathway,which facilitates the epithelial-mesenchymal transition(EMT)process.

Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C(UBE2C)and tripartite motif-containing protein 27(TRIM27)in patients with endometrial cancer(EC)and their correlation with pathological parameters.Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group;65 patients with endometrial atypical hyperplasia(EAH)as EAH group,and 80 healthy subjects as the control group.Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27.The relationship between serum UBE2C,TRIM27,and pathological data was analyzed;receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC.Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects(P<0.05),and was correlated with tumor diameter,tumor differentiation,lymph node metastasis,FIGO stage,muscle layer invasion depth,cervical involvement,estrogen receptor expression,and progestogen receptor expression(P<0.05).There was positive correlation between serum UBE2C and TRIM27(r=0.475,P<0.001);and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter,lymph node metastasis,FIGO stage,and depth of musclular invasion,but negatively with tumor differentiation,estrogen receptor expression,and progestogen receptor expression(P<0.05).The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection(ZUBE2C-combination=3.406,P<0.001,ZTRIM27-combination=3.285,P=0.001).Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated,which is closely related to pathological parameters.The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.

Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.