ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan （XJW）-containing serum interfering with endothelial-mesenchymal transition （EMT） in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW （4 g·kg^-1） to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum （4 g·kg^-1） according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group， β-catenin intervention/overexpression group， intervention/overexpression blank + XJW group， and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and active-Caspase-3］ and EMT-related proteins （E-cadherin， N-cadherin， and vimentin）. Real-time polymerase chain reaction （Real-time PCR） was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group， the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates （P<0.05， P<0.01）， elevated protein levels of Bax， active Caspase-3， and E-cadherin （P<0.05， P<0.01）， and decreased protein levels of Bcl-2 and Vimentin （P<0.05， P<0.01）. β-catenin mRNA expression was reduced in the β-catenin intervention group （P<0.05， 0.63 ± 0.15） and the intervention blank + XJW group （P<0.05， 0.79 ± 0.33）. Compared with the β-catenin intervention group， the β-catenin intervention + XJW group exhibited an increased apoptosis rate （P<0.01）， elevated Bax and active Caspase-3 protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and Vimentin protein levels （P<0.05）. β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group （P<0.01， 0.22 ± 0.08）. Compared with the intervention blank + XJW group， the β-catenin intervention + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax， active Caspase-3， and E-cadherin protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and vimentin protein levels （P<0.05， P<0.01）. β-catenin mRNA expression was also reduced （P<0.05）. Overexpression experiment results showed that compared with the overexpression blank group， the β-catenin overexpression group exhibited a reduced apoptosis rate （P<0.01）， while the overexpression blank + XJW group showed an increased apoptosis rate （P<0.05）. In the β-catenin overexpression and β-catenin overexpression + XJW groups， Bax and E-cadherin protein levels decreased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels increased （P<0.05）. In the overexpression blank + XJW group， Bax and E-cadherin levels increased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels decreased （P<0.05， P<0.01）. β-catenin mRNA expression increased in the β-catenin overexpression group （P<0.01， 7.26 ± 1.03） but decreased in the overexpression blank + XJW group （P<0.05， 0.73 ± 0.14）. Compared with the β-catenin overexpression group， the β-catenin overexpression + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax and E-cadherin levels （P<0.05）， and decreased N-cadherin and vimentin levels （P<0.05）. β-catenin mRNA expression was reduced （P<0.05， 4.65 ± 1.02）. Compared with the overexpression blank + XJW group， the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate （P<0.01）， decreased Bax and E-cadherin levels （P<0.01）， and increased Bcl-2， N-cadherin， and Vimentin levels （P<0.05）. β-catenin mRNA expression increased （P<0.01）. ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT， which is associated with the regulation of the Wnt/β-catenin pathway.

BACKGROUND:Osteoporosis affects the quality of life of patients and is prone to pathological fractures,and plant-derived exosome-like nanovesicles play an important role in regulating bone balance in patients with osteoporosis.OBJECTIVE:To review the research status and prospect of different plant-derived exosome-like nanovesicles in the treatment of osteoporosis.METHODS:Relevant literature in PubMed,Web of Science,and CNKI databases were searched by computer.Search time was from January 1995 to March 2024.The Chinese and English search terms were"osteoporosis,plant-derived exosome-like nanovesicles,exosomes,osteoblasts,osteoclasts."Finally,53 articles were included and analyzed.RESULTS AND CONCLUSION:Plant-derived exosom-like nanovesicles have the advantages of low biocompatibility,low toxicity,and natural targeting.These properties not only ensure its stable presence and effective effect in the body,but also avoid unnecessary immune responses,laying the foundation for the design of long-term treatment strategies.Plant-derived exosome-like nanovesicles can be anti-osteoporosis by stimulating osteoblast proliferation,inhibiting osteoclast differentiation,and promoting osteo-inhibition osteoclasts.In addition,some plant-derived exosome-like nanovesicles may be widely used in the diagnosis and treatment of osteoporosis in the future as novel tracer targets and treatment options due to their bone-targeting.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

BACKGROUND:Osteoporosis affects the quality of life of patients and is prone to pathological fractures,and plant-derived exosome-like nanovesicles play an important role in regulating bone balance in patients with osteoporosis.OBJECTIVE:To review the research status and prospect of different plant-derived exosome-like nanovesicles in the treatment of osteoporosis.METHODS:Relevant literature in PubMed,Web of Science,and CNKI databases were searched by computer.Search time was from January 1995 to March 2024.The Chinese and English search terms were"osteoporosis,plant-derived exosome-like nanovesicles,exosomes,osteoblasts,osteoclasts."Finally,53 articles were included and analyzed.RESULTS AND CONCLUSION:Plant-derived exosom-like nanovesicles have the advantages of low biocompatibility,low toxicity,and natural targeting.These properties not only ensure its stable presence and effective effect in the body,but also avoid unnecessary immune responses,laying the foundation for the design of long-term treatment strategies.Plant-derived exosome-like nanovesicles can be anti-osteoporosis by stimulating osteoblast proliferation,inhibiting osteoclast differentiation,and promoting osteo-inhibition osteoclasts.In addition,some plant-derived exosome-like nanovesicles may be widely used in the diagnosis and treatment of osteoporosis in the future as novel tracer targets and treatment options due to their bone-targeting.

Objective:To evaluate the safety, effectiveness, and long-term efficacy of the Jinling procedure for management of refractory mixed constipation.Methods:We prospectively collected clinical data of patients with refractory mixed constipation treated by the Jinling procedure in the Institute of General Surgery of our hospital from January 2007 to August 2023. Perioperative complications, effectiveness within 1 year of surgery (as assessed by the Wexner constipation score, gastrointestinal quality of life index, frequency of spontaneous defecation, rate of satisfactory defecation, body composition, serological indicators, defecography, anorectal manometry) and 10 years after surgery (as assessed by the Wexner constipation score, patient assessment of constipation symptom, SF-36 quality of life score, and questionnaire concerning satisfaction with defecation).Results:The study cohort comprised 3310 patients of mean age 44±15 years, including 653 men and 2657 women. The duration of constipation was 141±114 months. The 1-month, 3-month, 6-month, and 12-month follow-up rates were 98.07% (3246/3310), 95.11% (3148/3310), 93.38% (3091/3310), and 92.81% (3072/3310), respectively. Overall, 1100 patients had undergone surgery at least 10 years previously, 683 of whom completed the questionnaire, making the 10-year follow-up rate 62.09%. The overall incidence of postoperative complications was 21.99% (728/3310), mortality 0.45% (15/3310), and duration of postoperative hospital stay 12.5±5.4 days. Compared with preoperative values, Wexner scores decreased significantly from 1 to 12 months after surgery, whereas the gastrointestinal quality of life index scores had gradually increased by 3 months after surgery; both changes were statistically significant (both P < 0.001). The frequency of spontaneous defecation increased significantly to > five times/day 1 month after surgery, following which it decreased gradually with time, falling to two to five times/day by 6 months after surgery. All nutritional indicators returned to preoperative levels within 1 year except for that of inorganic salt, which did not change significantly. By 6–12 months after surgery, the proportions of rectocele, mucosal prolapse, internal rectal intussusception, visceral ptosis, perineal descent, pelvic floor spasm, and puborectalis syndrome assessed by defecography were all significantly lower than before surgery (all P < 0.05). By 3 months after surgery, the anal resting pressure, anal maximum systolic pressure, and anorectal depression had all returned to preoperative levels. Twelve months after surgery, the rectoanal inhibition reflex was stronger than that before surgery, whereas anal relaxation was less pronounced than that before surgery; these differences are statistically significant (both P < 0.05). The Wexner scores (7±2 vs. 21±6) and patient assessment of constipation symptoms scores (13±5 vs. 39±5) were significantly lower 10 years after the Jinling procedure than they had been before surgery. The eight dimensions of the SF-36 quality of life scores for physical functioning (90±5 vs. 78±8), role limitations in physical functioning (89±12 vs. 50±24), bodily pain (67±18 vs. 33±22), emotional well-being (63±23 vs. 48±30), vitality (71±11 vs. 31±13), mental health (71±10 vs. 30±10), social functioning (69±17 vs. 26±15) and general health (79±9 vs. 35±12) had all improved significantly (all P < 0.001). The total rates of satisfaction with defecation were 95.02% (2919/3072) and 87.56% (598/683) 1 year and 10 years after surgery, respectively. Conclusion:The Jinling procedure is a safe and effective means of treating refractory mixed constipation, achieving improvement in long-term defecation function and gastrointestinal quality of life.