OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To explore the experiences of children with Crohn's disease and their parents regarding the exclusion diet,and to provide a basis for formulating personalized dietary guidance programs.Methods A total of 12 children with Crohn's disease and their parents,hospitalized in the Department of Gastroenterology at a tertiary children's hospital in Guangzhou from June to December 2023,were selected as research subjects using objective sampling.Semi-structured interviews were conducted,and the data were analyzed and refined using Colaizzi's seven-step analysis method.Results Totally 3 themes and 14 sub-themes were extracted.①Lack of cognition and trust in Crohn's disease exclusion diet(unfamiliarity with the contents of the diet,misunderstanding of the diet's preparation,inadequate response to daily exclusion diet practices,parents' distrust in the exclusion diet).②The practical challenges of the Crohn's disease exclusion diet(the challenge of personal dietary preferences,the challenge of family meal preparation,the challenge of school feeding,food intolerance,feelings of monotony and weariness following the exclusion diet).③Innovations in practicing the Crohn's disease exclusion diet(managing taste fatigue,managing visual fatigue,innovative cooking methods,prioritizing exclusive enteral nutrition followed by the exclusion diet,overcoming the desire for universal food).Conclusion Children with Crohn's disease and their parents exhibit insufficient cognition and trust in the exclusion diet and face various challenges in practice.Clinical medical staff should adopt personalized coping strategies tailored to the specific circumstances of each child.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.

Objective·To evaluate the detection efficacy and clinical value of non-invasive prenatal testing(NIPT)for identifying copy number variations(CNVs)in the recurrent 17p12 region,including the peripheral myelin protein 22(PMP22)gene.Methods·Pregnant women who underwent NIPT in the International Peace Maternity & Child Health Hospital,Shanghai Jiao Tong University School of Medicine between July 2020 and April 2024 were enrolled.Clinical data of individuals indicated as high-risk for microdeletions/duplications in the 17p12 region based on NIPT results were collected.Follow-up was conducted to assess the results of subsequent prenatal diagnosis and chromosomal microarray analysis(CMA)performed on peripheral blood from both the pregnant women and their husband.The positive predictive value(PPV)of NIPT for detecting microdeletions/duplications in the 17p 12 region,as well as the underlying causes of false positives,was analyzed.Pregnancy outcomes and related clinical phenotypes of fetuses and pregnant women diagnosed with 17p12 CNVs were followed up.Results·A total of 61 858 pregnant women underwent NIPT testing.NIPT identified 24 cases(0.04％)as high-risk for CNVs in the 17p12 region,including six cases of high-risk 17p12 microduplication and 18 cases of high-risk 17p12 microdeletion.All 24 pregnant women received genetic counseling,and 21(87.50％)underwent invasive prenatal diagnosis.Invasive prenatal diagnostic confirmed four fetuses with 17p12 microduplications,nine fetuses with 17p12 microdeletions,and eight fetuses with no abnormalities,yielding a PPV of 61.90％(13/21).CMA analysis of maternal peripheral blood in the eight false-positive cases revealed that all mothers carried 17p12 CNVs.Further analysis of pregnant women with NIPT-indicated maternal CNVs revealed that all of them carried relevant CNVs.Among the 20 women with successful follow-up,the majority had normal deliveries,with only one case choosing to terminate the pregnancy due to a de-novo fetal 17p12 microduplication.Normally delivered fetuses(average age:1.5 years)were followed up without reporting any significant abnormalities.Of the 16 pregnant women carrying 17p12 CNVs,only two exhibited clinical phenotypes associated with these CNVs,while the others remained asymptomatic.Conclusion·NIPT demonstrates favorable detection efficacy for CNVs in the 17p12 region.Maternal CNVs are the primary cause of false-positive NIPT results for this region.