Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

[Objective] To explore the predictive value of HALP score for prognosis in patients with multiple myeloma (MM). [Methods] A retrospective analysis was conducted on laboratory indicators and related clinical data of newly diagnosed multiple myeloma (NDMM) patients, treated at the Affiliated Hospital of North Sichuan Medical College from January 2016 to October 2023, prior to their first treatment. The HALP score was calculated, and the optimal cutoff value for HALP was determined using X-tile software. Survival analysis was performed using Kaplan-Meier curves for high HALP and low HALP groups. Univariate and multivariate analyses were conducted using the Cox regression model, and a forest plot was generated using Graphpad Prism to illustrate factors that may impact patient prognosis. The predictive ability of HALP score combined with β2-microglobulin and ECOG score for prognosis in MM patients was evaluated using receiver operating characteristic curve (ROC) analysis. [Results] A total of 203 MM patients were included, with the optimal cutoff value for HALP score being 29.15 (P<0.05). Among them, 101 patients were in the low HALP score group, and 102 patients were in the high HALP score group. The results of univariate and multivariate analysis using the Cox regression model showed that a HALP score <29.15 was an independent risk factor for progression-free survival (PFS) and overall survival (OS) (P<0.05). ROC curve analysis indicated that the combination of HALP score with β2-microglobulin and ECOG score had a higher predictive value for prognosis in MM patients compared to using HALP score alone. [Conclusion] The HALP score is closely related to the prognosis of patients with NDMM. A low HALP score indicates a poorer prognosis, while the combination of HALP score with β2-microglobulin and ECOG score provides a higher predictive value when assessed together.

Objective:To evaluate the factors influencing test failure after resampling in non-invasive prenatal testing (NIPT) and to explore its impact on pregnancy outcomes.Methods:The information of pregnant women who failed to undergo NIPT for the first time and resampled for testing in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to January 2022 were collected and retrospectively analyzed. According to the results of resampled NIPT, the pregnant women were divided into the failure group (170 cases) and the success group(485 cases), and the general clinical data and pregnancy outcomes of the two groups were compared.Results:(1) A total of 88 928 pregnant women underwent NIPT in Beijing Obstetrics and Gynecology Hospital during the study period, of which 1 299 (1.461%, 1 299/88 928) failed in the first NIPT. Among the 1 299 pregnant women who failed in the first NIPT, 720 were resampled for testing. Finally, 655 pregnant women who met the inclusion criteria and had complete clinical information and perinatal outcomes were collected. The success rate of resampling was 74.0% (485/655). Compared with the success group, the pregnant women in the failure group had a later gestational age at resampling, a higher pre-pregnancy body mass index (BMI) and a higher fetal fraction, and the differences were statistically significant (all P<0.001). (2) Among the 485 pregnant women in the success group, 130 cases (26.8%, 130/485) were detected with chromosome aneuploidy. Among the 170 pregnant women in the failure group, 8 cases had abnormal amniocentesis, 2 cases had abnormal maternal serum screening of aneuploidy in the second trimester, 3 cases had abnormal ultrasound anomaly removal, and 157 cases had no abnormality. (3) The incidence of fetal or neonatal malformation in the failure group was significantly higher than that in the success group [11.2% (19/170) vs 5.8% (28/485), P=0.019], but after adjusting for age and pre-pregnancy BMI, fetal or neonatal malformation was not associated with the success of resampling ( RR=0.675, 95% CI: 0.346-1.319; P=0.250). The incidences of gestational diabetes mellitus and hypertensive disorders in pregnancy in the failure group were significantly higher than those in the success group (all P<0.05), but after adjusting for age and pre-pregnancy BMI, only the incidence of gestational diabetes mellitus in the failure group was higher ( RR=0.630, 95% CI: 0.426-0.932; P=0.021). Conclusions:For pregnant women who failed the initial NIPT, the success of the resampling test is associated with pre-pregnancy BMI and the gestational week at the time of resampling. Those who failed the resampling test are more likely to develop gestational diabetes mellitus. When providing genetic counseling for pregnant women who failed the initial NIPT, it is important to consider the successful rate of resampling testing. The risk of chromosomal abnormalities should be comprehensively considered to develop further screening strategies.

Objective:To analyze the clinical characteristics, diagnosis and prognosis of pregnant women with fetomaternal hemorrhage (FMH) syndrome, and to guide the management of pregnant women with FMH syndrome.Methods:The clinical data of 33 pregnant women with FMH syndrome admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2010 to December 2024 were collected, and the general information, diagnostic characteristics, treatment and maternal and fetal prognosis were retrospectively analyzed.Results:The incidence of FMH syndrome in our hospital was 1.7/10 000 (33/194 272). The gestational age of onset of FMH syndrome in 33 pregnant women was (35.6±3.1) weeks, 15 cases (45%, 15/33) were full-term delivery and 18 cases (55%, 18/33) were preterm delivery. Decreased fetal movement (51%, 17/33) was the most common initial symptom, followed by abnormal electronic fetal monitoring (33%, 11/33). Thirty-two cases (97%, 32/33) underwent cesarean section, and only one case had spontaneous delivery. Postpartum hemorrhage occurred in 11 cases (33%, 11/33). All the neonates were transferred to neonatal intensive care unit for treatment. Two of them were treated with intrauterine blood transfusion, and the neonates did not receive blood transfusion after birth. The neonatal mortality rate was 6% (2/33), and the remaining 31 cases (94%, 31/33) survived. Complications occurred in 3 premature infants, including 1 case of neonatal neurodevelopmental disorder with cochlear implantation, 1 case of pulmonary artery stenosis, and 1 case of retinopathy of prematurity. Three pregnant women were pregnant again, and none of them had FMH syndrome.Conclusions:Decreased fetal movement or abnormal electronic fetal monitoring in late pregnancy should be alert to the occurrence of FMH syndrome. Early diagnosis and intervention are critical to improve the prognosis of FMH syndrome.

Objective To explore the correlation between thyroid autoimmunity(TAI)and gestational diabetes mellitus(GDM)in Chinese euthyroid women.Methods A total of 508 euthyroid women were enrolled in the cross-sectional study,who performed their entire clinical/biological workup and oral glucose tolerance test(OGTT)from the department of Gynecology and Endocrinology of the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from June 2023 to June 2024.At median 8(6-10)weeks of gestation,thyroid-stimulating hormone(TSH),free thyroxine(fT4),and thyroid peroxidase antibodies(TPOAb)were measured,baseline characteristics were recorded,and an OGTT was performed between 24 and 28 weeks of pregnancy.According to the OGTT results,they were divided into GDM group(n=169)and non GDM group(n=339).Thyroid parameters,the demographic and obstetric parameters,and the prevalence of TAI were compared with two groups.The factors associated with GDM were analyzed with multivariate Logistic regression analysis.Results The age,body mass index(BMI),and proportion of obese women before pregnancy in the GDM group were all significantly higher than those in the non-GDM group,with statistically significant differences(P<0.001).The proportion of pregnant women over 30 years old in the GDM group was significantly higher than that in the non-GDM group(59.17%vs 6.79%,χ2=168.667,P<0.001).The proportion of obese mothers(BMI≥28 kg/m2)before pregnancy in the GDM group was 24.26%,which was significantly higher than that in the non-GDM group(8.26%)(χ2=24.599,P<0.001).The incidence of TAI in the GDM group was 54.44%,while it was 15.93%in the non-GDM group.The difference between the two groups was statistically significant(χ2=81.659,P<0.001).The results of Logistic regression analysis showed that maternal age over 30 years and pre-pregnancy obesity increased the risk of GDM occurrence in TAI women by 6.08 times(OR=6.08,95%CI 3.61-10.25,P<.001).Conclusion Among early pregnancy women with normal thyroid function,as age increases during follow-up(especially over 30 years old),pre-pregnancy BMI increases(especially in obese individuals),and those with pre-pregnancy TAI,the risk of developing GDM during pregnancy significantly increases.It is necessary to explore preventive strategies for GDM in euthyroid TAI women,with a view to improving adverse pregnancy outcomes.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Objective:To explore the correlation between water-soluble vitamin levels and clinical indicators and provide a theoretical basis for precise nutrition treatment of chronic kidney disease (CKD) .Methods:Clinical data of CKD patients who underwent water-soluble vitamin (B1, B2, B6, B9, B12, C) level tests at the First Affiliated Hospital, Army Medical University from Jan. 2016 to Dec. 2023 were collected and analyzed to investigate the relationship between water-soluble vitamin levels and clinical indicators.Results:The median values of B1 and B2 were 47.52 (range 41.65-135.36) and 184.52 (range 178.52-192.53), which were below the normal range. The results showed that age, serum creatinine, and fasting blood glucose in the low-level group for all vitamins were higher than those in the high-level group ( P<0.05). However, hemoglobin and estimated glomerular filtration rate were lower in the low-level group than those in the high-level group ( P<0.05). In the low-level group of B1, the percentage of neutrophils (NEUT%) was higher than that in the high-level group ( P<0.05). In CKD stage 5, the levels of all vitamins were lower than those of CKD stage 1 ( P<0.05). Spearman correlation analysis showed that the levels of all vitamins were negatively correlated with CKD stage, with correlation coefficients of -0.329, -0.357, -0.345, -0.373, -0.386 and-0.351, respectively ( P<0.01) . Conclusions:Metabolic abnormalities of watersoluble vitamins are common in CKD, which are closely related to the progression of CKD, inflammation and anemia. Timely evaluation and intervention may be beneficial to prevent the progression of CKD and provide a new treatment strategy for precise nutrition intervention in CKD.

Objective To explore the correlation between thyroid autoimmunity(TAI)and gestational diabetes mellitus(GDM)in Chinese euthyroid women.Methods A total of 508 euthyroid women were enrolled in the cross-sectional study,who performed their entire clinical/biological workup and oral glucose tolerance test(OGTT)from the department of Gynecology and Endocrinology of the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from June 2023 to June 2024.At median 8(6-10)weeks of gestation,thyroid-stimulating hormone(TSH),free thyroxine(fT4),and thyroid peroxidase antibodies(TPOAb)were measured,baseline characteristics were recorded,and an OGTT was performed between 24 and 28 weeks of pregnancy.According to the OGTT results,they were divided into GDM group(n=169)and non GDM group(n=339).Thyroid parameters,the demographic and obstetric parameters,and the prevalence of TAI were compared with two groups.The factors associated with GDM were analyzed with multivariate Logistic regression analysis.Results The age,body mass index(BMI),and proportion of obese women before pregnancy in the GDM group were all significantly higher than those in the non-GDM group,with statistically significant differences(P<0.001).The proportion of pregnant women over 30 years old in the GDM group was significantly higher than that in the non-GDM group(59.17%vs 6.79%,χ2=168.667,P<0.001).The proportion of obese mothers(BMI≥28 kg/m2)before pregnancy in the GDM group was 24.26%,which was significantly higher than that in the non-GDM group(8.26%)(χ2=24.599,P<0.001).The incidence of TAI in the GDM group was 54.44%,while it was 15.93%in the non-GDM group.The difference between the two groups was statistically significant(χ2=81.659,P<0.001).The results of Logistic regression analysis showed that maternal age over 30 years and pre-pregnancy obesity increased the risk of GDM occurrence in TAI women by 6.08 times(OR=6.08,95%CI 3.61-10.25,P<.001).Conclusion Among early pregnancy women with normal thyroid function,as age increases during follow-up(especially over 30 years old),pre-pregnancy BMI increases(especially in obese individuals),and those with pre-pregnancy TAI,the risk of developing GDM during pregnancy significantly increases.It is necessary to explore preventive strategies for GDM in euthyroid TAI women,with a view to improving adverse pregnancy outcomes.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.