OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.
Humans ; Drug Delivery Systems/methods* ; Ischemic Stroke/drug therapy* ; Animals ; Blood-Brain Barrier/metabolism* ; Stroke/drug therapy*

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

The 2025 American Thyroid Association Guidelines for the Management of Differentiated Thyroid Cancer in Adults incorporate the latest evidence-based medical research to systematically update the strategies for diagnosis, treatment, and follow-up of thyroid cancer. Integrating multidisciplinary perspectives from internal medicine, surgery, radiology, pathology, and other fields—and for the first time including input from patient representatives—the guidelines comprehensively cover the entire management process of differentiated thyroid cancer, significantly enhancing their clinical applicability. Regarding the current focus on active surveillance, the new edition provides clear recommendations based on a rigorous evaluation of existing evidence and multidisciplinary input. This article reviews and discusses key updates and practical aspects of the active surveillance section in the guidelines, with reference to relevant Japanese and Korean guidelines, with the aim of improving the application of active surveillance in thyroid cancer management.

Objective To investigate the influence of intravenous esketamine infusion on anesthetic effect and awakening quality in elderly patients undergoing laparoscopic surgery for prostate cancer.Methods One hundred and twenty patients with laparoscopic radical prostatectomy were selected and divided into the esketamine group(group E)and control group(group C)by the random number table method,60 ca-ses in each group.The group E used esketamine for anesthesia induction and maintenance,while the group C received the same amount of physiological saline at the same time during operation process as control.The es-ketamine pumping infusion or normal saline in the two groups was stopped at 30 min before operation end.In addition,the types and doses of other drugs used during the induction and maintenance phase of anesthesia were identical between the two groups.The use total amounts of anesthetic drugs during perioperative period were recorded.The heart rate(HR)and mean arterial pressure(MAP)were recorded before operation(T1),instantly before tracheal intubation(T2),at 1 min after tracheal intubation(T3),1 h during surgery(T4),end of skin suture(T5),and 5 min after extubation(T6)in the two groups respectively;the anesthetic recovery time after extubation was recorded.The Riker sedation and restlessness score was used to conduct the agita-tion evaluation,the incidence rates of agitation and bucking and the resuscitation room stay time were recor-ded.The pain VAS score was used to conduct the pain evaluation in the patients.The incidence rates of ad-verse events such as respiratory depression,shiverring,nausea,vomiting,drowsiness after extubation were re-corded.Results The perioperative doses of resutanil and propofol in the group E were significantly lower than those in the group C,and the difference was statistically significant(P＜0.05).HR and MAP at T2 in the group E were higher than those in the group C,while HR and MAP at T3 in the group E were lower than those in the group C.The recovery time after extubation in the group E was longer than that in the group C,the agitation incidence rate,acute bucking incidence rate and VAS score were lower,the stay time in the recov-ery room was shorter.The incidence rate of drowsiness in the group E was significantly higher than that in the group C(P＜0.05).The incidence rates of other adverse events had no statistical differnece(P＞0.05).Con-clusion Esketamine is safe and effective in the elderly patients with laparoscopic prostate cancer surgery,which is conducive to stabilize the hemodynamic parameters and reduce the incidence rate of agitation and buc-king.

Based on the core collection retrieval of the Web of Science database,researches related to the medicinal field of plant-derived vesicles(PDVs)were retrieved.The research hotspots and their changes in the pharmaceutical field of PDVs are visually analyzed by using bibliometric software VOSviewer and CiteSpace.A detailed discussion is held around the author,institution,country,key research hotspots and annual develop-ment hotspots,revealing the current research status of PDVs in the pharmaceutical field and predicting future trends,which provides valuable perspectives for researchers to understand the current research status of PDVs in the pharmaceutical field and discover possible unexplored areas in this field.

Papillary thyroid microcarcinoma(PTMC),which lacks lymph node metastasis,distant metastasis,extra-thyroid invasion,high-risk subtypes,and invasion of the trachea or recurrent laryngeal nerve,may be classified as low-risk PTMC based on clinical assessment.Surgical intervention such as lobectomy or total thyroidectomy is the primary treatment modality for PTMC.This study comprised 124 patients who underwent conformal thyroidectomy and revealed that this innovative surgical approach yielded long-term oncological outcomes comparable to those who received lobectomy or total thyroidectomy.The surgical intervention may play a significant role in the comprehensive management of PTMC,while the implementation of PTMC precision medicine necessitates the utilization of genetic testing,molecular typing,and other advanced technologies to detect early-stage high-risk factors like lymph node microinvasion and integrate biology-based surgery concept for optimal outcomes.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

Objective:To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma(RAML)with rupture and hemorrhage.Methods:The demographic data and peri-operative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected.The surgery within 7 days after hemorrhage was defined as a short-term surgery group,the surgery between 7 days and 6 months after hemorrhage was defined as a me-dium-term surgery group,and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group.The perioperative related indicators among the three groups were compared.Results:This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage,of whom 13 were males and 18 were females,with an average age of(46.2±11.3)years.The short-term surgery group included 7 patients,the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients.In terms of tumor diameter,the patients in the long-term surgery group were significantly lower than those in the recent surgery group[(6.6±2.4)cmvs.(10.0±3.0)cm,P=0.039].In terms of operation time,the long-term surgery group was significantly shorter than the mid-term surgery group[(157.5±56.8)min vs.(254.8±80.1)min,P=0.006],and there was no sig-nificant difference between other groups.In terms of estimated blood loss during surgery,the long-term surgery group was significantly lower than the mid-term surgery group[35(10,100)mL vs.650(300,1 200)mL,P＜0.001],and there was no significant difference between other groups.In terms of intraoperative blood transfusion,the long-term surgery group was significantly lower than the mid-term surgery group[0(0,0)mL vs.200(0,700)mL,P=0.014],and there was no significant difference between other groups.In terms of postoperative hospitalization days,the long-term surgery group was sig-nificantly lower than the mid-term surgery group[5(4,7)d vs.7(6,10)d,P=0.011],and there was no significant difference between other groups.Conclusion:We believe that for patients with RAML rupture and hemorrhage,reoperation for more than 6 months is a relatively safe time range,with minimal intraoperative bleeding.Therefore,it is more recommended to undergo surgical treatment after the hema-toma is systematized through conservative treatment.