ObjectiveTo investigate the mechanism through which Wendan Tang ameliorates atherosclerosis （AS） in mice by regulating ferroptosis via the Janus kinase 2（JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsTwelve 8-week-old male C57BL/6J mice of SPF grade were selected as the blank control group and fed a standard diet. Additionally， sixty age-matched male apolipoprotein E knockout （ApoE^-/-） mice of the same strain and SPF grade were selected and assigned through a random number table into the following groups （n=12 per group）： a model group， a low-dose （3.9 g·kg^-1·d^-1） Wendan Tang group， a medium-dose （7.8 g·kg^-1·d^-1） Wendan Tang group， a high-dose （15.6 g·kg^-1·d^-1） Wendan Tang group， and an atorvastatin calcium （0.01 g·kg^-1·d^-1） group. All ApoE^-/- mice were fed a high-fat diet for the modeling of AS. Starting from week 9， the blank and model groups were administrated with an equal volume of normal saline by gavage， and the remaining groups with corresponding agents by gavage. After 8 weeks of intervention， samples were collected for analysis. Oil red O staining and Masson staining were used to observe lipid deposition in the aorta， and hematoxylin-eosin （HE） staining was employed to examine AS plaque formation. The serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， and reduced glutathione （GSH） were determined by enzyme-linked immunosorbent assay （ELISA）. The level of Fe²⁺ in the aortic tissue was measured by ELISA. Western blot was performed to determine the protein levels of JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， phosphorylated STAT3 （p-STAT3）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the mRNA levels of JAK2， STAT3， SLC7A11， and GPX4 in the aortic tissue. ResultsCompared with the blank control group， the model group exhibited increased aortic plaque number and area， enhanced lipid deposition， elevated serum levels of TC， TG， LDL-C， TNF-α， IL-6， and MDA （P<0.05， P<0.01）， declined serum levels of HDL-C， SOD， and GSH， and downregulated protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）. The aortic tissue of the model group exhibited an elevated Fe²⁺ level and upregulated protein levels of p-JAK2 and p-STAT3 and mRNA levels of JAK2 and STAT3 （P<0.05， P<0.01）. Compared with the model group， low-， medium-， and high-dose Wendan Tang， as well as atorvastatin calcium， significantly attenuated these pathological alterations. Specifically， the treatments decreased aortic plaque burden and lipid deposition and lowered serum TC， TG， LDL-C， TNF-α， and MDA levels （P<0.05， P<0.01）. Concurrently， these interventions raised serum HDL-C， SOD， and GSH levels， upregulated the protein levels of SLC7A11 and GPX4 in the aortic tissue （P<0.05， P<0.01）， reduced the Fe²⁺ level， and downregulated the protein levels of p-JAK2 and p-STAT3 and the mRNA levels of JAK2 and STAT3 in the aortic tissue （P<0.05， P<0.01）. ConclusionWendan Tang ameliorates aortic lesions， dyslipidemia， and oxidative stress， decreased the phosphorylation levels of JAK2/STAT3， and increased the expression of SLC7A11 and GPX4 in the mouse model of AS. The results suggest that the anti-AS effect of Wendan Tang may be associated with the modulation of the JAK2/STAT3 signaling pathway and inhibition of ferroptosis.

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

Objective:To compare the clinical value of digital breast tomosynthesis (DBT) localization and stereotactic positioning biopsy of breast lesions.Methods:This study was a cross-sectional study. Totally of 250 patients who underwent breast biopsy at Shenzhen People′s Hospital, Luohu District People′s Hospital and Peking University Shenzhen Hospital between August 2021 to October 2023 was analyzed retrospectively, including 136 cases of DBT-guided biopsy (DBT-guided group) and 114 cases of stereotactic-guided biopsy (stereotactic-guided group). The stereotactic-guided biopsy methods included core needle biopsy (CNB) and wire positioning. The DBT-guided biopsy methods included CNB, wire positioning and vacuum-assisted breast biopsy (VABB). The χ2 test or Mann-Whitney U test was used to compare the puncture success rate, operation time, localization time, puncture time, number of first valid localization phases obtained, number of exposures, and complications of different biopsy methods between 2 groups. Results:In the wire positioning biopy, the puncture success rate was 100% (33/33) in DBT-guided group and 96% (48/50) in the stereotactic-guided group, with no statistically significant difference between the two groups ( P=0.515). Compared to the stereotactic-guided group, the operation time and localization time were shorter, and the number of first valid localization phases obtained, number of exposures were fewer in the DBT-guided group( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.871). In CNB, both the DBT-guided group and the stereotactic-guided group had higher puncture success rates, with no statistically significant difference ( P=0.080). Compared to the stereotactic-guided group, the operation time, localization time and puncture time were shorter, and the number of first valid localization phases obtained, number of exposures were lower in the DBT-guided group, and the difference between the two groups were statistically significant ( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.627). Twenty-one cases received DBT-guided VABB, with an operation time of (19.90±3.38) min, a localization time of 6.00 (6.00, 7.00) min, a puncture time of (13.42±3.28) min, the number of first effective localization phases obtained was 1.00 (1.00, 1.00) time, the number of exposures was 4.00 (3.50, 5.00) times, and one case experienced severe pain after puncture. Conclusion:Compared with stereotactic-guided biopsy, DBT-guided biopsy can reduce operation time and exposure times, and can target more types of breast lesions, with higher clinical application value.

Objective: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. Methods: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). Results: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. Conclusions The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

Objective:To retrospectively analyze the relationship between patterns of local recurrence and radiotherapy target dose after adjuvant radiotherapy for the pancreatic ductal adenocarcinoma(PDAC), aiming to provide reference for exploring reasonable target and dosage.Methods:Clinical data of 138 patients with T 1-4N 0-2M 0 PDAC who underwent adjuvant radiotherapy after radical resection from April 2012 to December 2020 were analyzed retrospectively. The influencing factors of local recurrence and the correlation between local recurrence site and radiotherapy target dose were analyzed. Results:The median follow-up time was 37.2 months. The median overall survival (mOS) was 29.9 months. The 5-year OS rate was 27.4%. And the median progression-free survival (mPFS) was 13.9 months. There were 24 cases of local recurrence (17.4%), and 10 cases of local recurrence complicated with distant metastasis (7.2%). The correlation between local recurrence site and radiotherapy target dose could be evaluated in 19 patients with complete clinical data. The first local recurrence occurred near the para-aortic (Ao), the celiac axis (CA) and the superior mesenteric artery (SMA) were 8, 5 and 4 cases, respectively. The radiotherapy doses of 8 patients with local recurrence only in the PTV field were above 45 Gy. There were 8 cases of local recurrence both in and out of the PTV field, including 3 cases with dose line between 40 and 52 Gy, 2 cases with dose line between 20 and 47.5 Gy, and 3 cases with dose line between 0.5 and 52.5 Gy. There were 3 cases of local recurrence out of the PTV field, and the dose line ranged from 0 to 20 Gy.Conclusions:The local recurrence rate of PDAC after radical surgery combined with postoperative radiotherapy is low, but a small number of patients have recurrence in the high-dose range of radiation field and regional recurrence out of the field. For these patients, it may be necessary to explore a more appropriate target dose and range for adjuvant radiotherapy.

Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.

[This corrects the article DOI: 10.1016/j.apsb.2020.05.004.].

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:To study the incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and the gene carrying status of newborns in Guangxi Zhuang Autonomous Region (Guangxi for short), so as to provide theoretical basis for clinical genetic counseling and accurate diagnosis.Methods:A total of 63 606 newborns who underwent G6PD screening in Guangxi Neonatal Disease Screening Center from January 2017 to December 2018 were selected as study subjects; heel blood was collected to prepare dry blood spots. Fluorescence quantitative analysis was used in the preliminary screening, and the newborns with positive preliminary screening were recalled by telephone; further diagnosis was carried out via the G6PD/6-phosphogluconate dehydrogenase (6PGD) ratio method and genetic testing, the diagnosis rate of the two methods of newborns with positive preliminary screening were compared and analyzed, and genetic mutation testing was conducted.Results:Among 63 606 newborns who underwent G6PD preliminary screening, 4 267 newborns with G6PD positive were detected, and the positive rate of preliminary screening was 6.7%. Among them, the positive rates of preliminary screening of males and females were 10.3% (3 508/33 988) and 2.6% (759/29 618), respectively. The positive rate of preliminary screening of males was significantly higher than that of females ( P < 0.01). A comparative analysis of 777 newborns (519 males and 258 females) that underwent G6PD/6PGD ratio method and genetic testing at the same time as the recall showed that the diagnosis rate of the two methods for male newborns was the same, both of which were 95.6% (496/519). Among female newborns, 168 and 236 confirmed cases were detected by G6PD/6PGD ratio method and genetic testing, respectively, and the diagnosis rates were 65.1% (168/258) and 91.5% (236/258), respectively. The results of genetic mutation testing showed that the five common genotypes in Guangxi were c.1388 G>A, c.1376 G>T, c.95 A>G, c.871 G>A, and c.1024 C>T, respectively. Conclusions:The positive rate of G6PD preliminary screening of newborns in Guangxi is relatively high. It is recommended that G6PD/6PGD ratio method and genetic testing should be performed at the same time for diagnosis of female newborns with positive preliminary screening to avoid missed diagnosis and misdiagnosis.