This article systematically analyzed the historical evolution of the origin， scientific name， producing area， quality evaluation， harvesting and processing， and other aspects of Quisqualis Fructus by consulting the ancient materia medica， medical books， prescription books， local literature and combining with the modern literature and standards， summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes， in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty， and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty， which has been consistently used throughout subsequent dynasties， and there were also aliases such as Junziren， Sijunzi， and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica， a plant belonging to the family Combretaceae. In modern times， its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007， the Flora of China（English edition） designated Q. indica var. villosa as a synonym of Q. indica. Today， the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records， the producing areas of Quisqualis Fructus were Guangdong， Hong Kong， Macao， Guangxi， Hainan， Sichuan and Fujian， and then gradually expanded to Yunnan， Taiwan， Jiangxi and Guizhou. Since the Song dynasty， two major production regions have gradually emerged in Sichuan， Chongqing and Fujian. Currently， it is primarily cultivated in Chongqing， Guangxi and other areas， with Chongqing yielding the highest output. Since modern times， superior quality has been defined by large size， a purple-black surface， plump grains， and a yellowish-white kernel. According to ancient herbal records， the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar， mostly used raw after shelling or with the shell intact， it underwent processing methods such as cleaning， slicing， mixing， steaming， roasting， stewing， and frying. Currently， the harvesting period is autumn， followed by sun-drying or low-heat drying， with processing methods including cleaning， stir-frying， and stewing. In ancient and modern literature， the records of the properties， functions and indications of Quisqualis Fructus are basically the same， that is， sweet in taste， warm in nature， predominantly non-toxic， belonging to the spleen and stomach meridians. It possesses effects of insecticide， decontamination and invigorating spleen for ascariasis， enterobiasis， abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations， limiting use for those with spleen-stomach deficiency-cold， refraining from drinking hot tea during medication， and avoiding excessive intake. Based on the textual research， it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements， and the raw products is recommended for medicinal use if not specified.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Gastric outlet obstruction (GOO) is a condition characterized by a mechanical obstruction of the stomach or duodenum, caused by either benign or malignant disease. Traditionally, surgical gastrojejunostomy (SGJ) has been the standard treatment for malignant GOO and endoscopic stenting (ES) offers a less invasive option, but it often requires repeat interventions. Recently, endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE), an innovative technique, has been applied as an alternative to SGJ and ES for GOO patients. Direct EUS-GE, device-associated EUS-GE, and EUS-guided double balloon-occluded gastrojejunostomy bypass are the most commonly used techniques with reported technical success rates ranging from 80% to 100%, and clinical success rates between 68% and 100%. Adverse event (AE) rates range from 0% to 28.2% and the stent misdeployment is the most common while other AEs include abdominal pain, bleeding, infection, peritonitis, bowel perforation, gastric leakage, and stent migration. It is clear that EUS-GE may achieve a similar clinical success to SGJ with fewer AEs and a shorter hospital stay. Compared to ES, EUS-GE showed higher clinical success, fewer stent obstructions, and lower reintervention rates.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

ObjectiveTo construct a circRNA-miRNA-mRNA competitive endogenous RNA （ceRNA） network， to investigate its potential regulatory mechanism in a mouse model of autoimmune hepatitis （AIH） induced by concanavalin A （ConA）， and to verify the association between the expression of key genes and liver injury. MethodsHigh-throughput data were used to identify differentially expressed circRNAs， miRNAs， and mRNAs， and the Pearson correlation analysis and the Miranda program were used to predict the pairing relationships between miRNAs and mRNAs/circRNAs and construct a ceRNA network. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the differentially expressed genes in the network. A total of 12 specific pathogen-free male C57BL/6 mice were divided into control group and model group using a random number table， with 6 mice in each group. The mice in the model group were given injection of ConA via the caudal vein to establish a mouse model of AIH， and those in the control group were given injection of normal saline. The methods of qRT-PCR and Western blot were used to validate the expression levels of circ_0001577， miR-7055-3p， and Akt3. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured， as well as the content of malondialdehyde （MDA） and nitric oxide （NO） in liver tissue， and their correlation with gene expression was analyzed. The independent-samples t test was used for comparison of continuous data between two groups， and the Spearman correlation analysis was used to investigate the correlation between gene expression levels and liver injury indicators. ResultsA ceRNA network containing 5 795 circRNA-miRNA-mRNA pairings was constructed， and circ_0001577 was identified as the central gene. Compared with the control group， the model group had significant increases in the expression levels of circ_0001577 and Akt3 and a significant reduction in the expression of miR-7055-3p （all P<0.05）， and circ_0001577 was positively correlated with Akt3 （r=0.861， P<0.001）， while miR-7055-3p was negatively correlated with circ_0001577 and Akt3 （r=-0.644 and -0.855， both P<0.05）. Compared with the control group， the model group had a significantly higher protein expression level of Akt3 in the liver （1.04±0.10 vs 0.72±0.06， t=-6.49， P=0.001）， which was positively correlated with circ_0001577 （r=0.579， P=0.048） and was negatively correlated with miR-7055-3p （r=-0.891， P<0.001）. Compared with the control group， the model group had significant increases in the serum levels of ALT and AST and the content of MDA and NO in liver tissue （all P<0.05）， and these liver injury indicators were positively correlated with circ_0001577 and Akt3 （r=0.849， 0.865， 0.811， 0.801； 0.889， 0.954， 0.938， and 0.961， all P<0.05） and were negatively correlated with miR-7055-3p （r=-0.687， -0.818， -0.833， and -0.870， all P<0.05）； in addition， they were positively correlated with the protein expression level of Akt3 （r=0.648， 0.796， 0.848， and 0.860， all P<0.05）. ConclusionThis study shows that circ_0001577 promotes the expression of Akt3 by competitively adsorbing miR-7055-3p and relieving the inhibition of Akt3， thereby participating in the development and progression of AIH.

ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth， the rats were randomly divided into blank （NC） group， maternal-infant separation （MS） group， restraint stress （RS） group， maternal-infant separation combined with restraint stress （MRS） group， Wenyang group， Jieyu group， Wenyang Jieyu （XSF） group， and minocycline group. Maternal-infant separation was performed on day 5 （PD5）， followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group， Xiaoyao group， XSF group and minocycline group were 5.85， 12.03， 16.71 g·kg^-1 and 50 mg·kg^-1， respectively. Restraint stress was applied on PD90. The model was evaluated using glucose， social interaction， open field， and O-maze behavior tests， as well as high-performance liquid chromatography to measure serotonin， dopamine， and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 （Iba-1） protein， a marker of hippocampal microglia， was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of M1 markers， JAK2/STAT3 pathway-related genes， and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group， the MRS group exhibited depression-like behavior， with significantly decreased levels of neurotransmitters in the hippocampus （P<0.05， P<0.01）， increased expression of Iba-1 （P<0.01）， and elevated protein levels of JAK2 and STAT3 （P<0.05）. The mRNA expression levels of CD68， CD11b， IL-1β， JAK2， and STAT3 were significantly increased （P<0.01）， while IL-10 mRNA expression was significantly decreased （P<0.01）. Compared with the MRS group， the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups， the hippocampal neurotransmitter content was significantly increased （P<0.05， P<0.01）， and Iba-1 expression was significantly decreased （P<0.01）. The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68， CD11b， JAK2， STAT3， and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups （P<0.05， P<0.01）， while IL-10 mRNA expression was significantly increased （P<0.05， P<0.01）. ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.