This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

Objective:To investigate the efficacy and mechanism of static progressive stretch (SPS) with different parameters in the treatment of stiff knee in rats.Methods:Fifty-six male 8-week SD rats were randomly divided into an operation group ( n=48) and a blank group ( n=8, normal feeding rats without any treatment). The knee joints of the rats in the operation group were fixed with Kirschner wire for 4 weeks to create models of right knee flexion stiffness. The 42 rats with successful modeling were randomly divided into 6 groups ( n=7): the model group was executed and sampled after successful modeling, the spontaneous recovery group was not given any treatment after successful modeling, group T1 was given SPS treatment for 20 min once per day, group T2 was given SPS treatment for 30 min once per day, group T3 was given SPS treatment for 20 min once every 2 days, and group T4 was given SPS treatment for 30 min once every 2 days. After 16 days, the range of knee motion, number of myofibroblasts, and positive proportion of transforming growth factor- β1 (TGF- β1) in the joint capsule were detected and compared between groups. Results:The ranges of knee motion in the spontaneous recovery group and the 4 SPS treatment groups were significantly greater than those before treatment ( P<0.05), and the improvements in the range of knee motion in the 4 SPS treatment groups were significantly greater than that in the spontaneous recovery group ( P<0.05). The range of knee motion in group T2 (112.29°±1.89°) was improved the most significantly. The number of myofibroblasts was (23.72±10.75)/HP, which was significantly smaller than that in T3 group [(55.72±33.56)/HP] or in T4 group [(50.72±33.34)/HP] ( P<0.05). The positive proportions of TGF- β1 in the joint capsule in the 4 SPS treatment groups were significantly lower than that in the model group, and the positive proportion of TGF- β1 in the joint capsule in group T2 (0.51%±0.38%) was significantly lower than those in group T3 and T4 ( P<0.05). Conclusions:As SPS treatment can reduce the expression of TGF- β1 in the joint and inhibit the excessive proliferation of myofibroblasts to alleviate the pathological changes in a stiff knee, it has a significant effect on the stiff knee in rats. The SPS treatment for 30 minutes and once per day may lead to the best efficacy.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

Objective To analyze risk factors and pathogenic characteristics of intestinal colonization of carbape-nem-resistant Enterobacterales(CRE)in patients from intensive care unit(ICU).Methods A total of 392 ICU pa-tients who underwent intestinal CRE screening in a tertiary hospital in Changzhou from March to December,2023 were divided into the colonization group(n=42)and the non-colonization group(n=350)according to the screening results.Clinical data of patients,including age,gender,underlying diseases,malignant tumors,radiotherapy,chemotherapy,infection before the last screening,antimicrobial use,and invasive procedures were collected for the analysis on risk factors and pathogenicity.Results Among 42 patients with positive CRE screening results,44 CRE strains were detected,mainly Klebsiella pneumoniae(65.91％),followed by Escherichia coli(15.91％)and En-terobacter cloacae(13.64％).The average time from admission in ICU to positive screening results of intestinal CRE in the colonization group was 14 days.Long term use of carbapenem antibiotics(OR=1.47,95％CI:1.31-1.65),mechanical ventilation(OR=1.14,95％CI:1.06-1.22),and Enterobacterales infection(OR=10.10,95％CI:3.28-32.09)were independent risk factors for intestinal CRE colonization.Patients who received carbap-enem antibiotics for ≥15 days(x2=167.52,P＜0.001)and those who received mechanical ventilation for ≥15 days(x2=101.03,P＜0.001)had higher risks for intestinal CRE colonization.Conclusion In clinical practice,it is necessary to improve pathogen detection,treat Enterobacterales infection timely,choose carbapenem antibiotics carefully,shorten treatment course,actively evaluate indications for mechanical ventilation,and wean off ventilator timely.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

AIM: To analyze the diagnostic value of macular ganglion cell complex(mGCC)and thickness and visual field of peripapillary retinal nerve fiber layer(pRNFL)on neovascular glaucoma(NVG).METHODS: Retrospective study. A total of 92 patients(100 eyes)with NVG who were admitted to our hospital from January 2018 to October 2021 were selected. They were divided into 31 cases(32 eyes)with early NVG, 31 cases(36 eyes)with open angle glaucoma and 30 cases(32 eyes)with angle-closure glaucoma according to their pathology and term. Additionally, 50 cases(100 eyes)receiving health examination in our hospital at the same period were selected as the control group. Pearson correlation was used to analyze the correlation among mGCC, pRNFL thickness and mean deviation(MD), and the diagnostic efficiency of each index was studied by the receiver operating characteristic(ROC)curve.RESULTS: The levels of mGCC-average(a), mGCC-superior(s)and mGCC-inferior(i)in the patients with early NVG, open-angle glaucoma and angle-closure glaucoma were lower than those in the control group(all P<0.001). The levels of mGCC-a, mGCC-s and mGCC-i in the patients with early NVG and the open-angle glaucoma group were higher than those in the angle-closure glaucoma group(all P<0.001). The levels of mGCC-a, mGCC-s and mGCC-i in the patients with early NVG were higher than patients with open-angle glaucoma group(all P<0.001). The thickness of pRNFL-a, pRNFL-temporal(t), pRNFL-s, pRNFL-nasal(n), and pRNFL-i in the patients with early NVG, open-angle glaucoma and angle-closure glaucoma was lower than that in the control group, while the MD was higher than that in the control group(all P<0.001). The thickness of pRNFL-a, pRNFL-t, pRNFL-s, pRNFL-n and pRNFL-i in the patients with early NVG and the open-angle glaucoma was higher than that of patients with angle-closure glaucoma group, while the MD level was higher than that in the patients with angle-closure glaucoma(all P<0.001). The thickness of pRNFL-a, pRNFL-t, pRNFL-s, pRNFL-n and pRNFL-i in the patients with early NVG was higher than that in the patients with open-angle glaucoma, while the MD level was higher than that those with open-angle glaucoma(all P<0.001). The mGCC-a, mGCC-s, mGCC-i, and the thickness of pRNFL-a, pRNFL-t, pRNFL-s, pRNFL-n, and pRNFL-i had a negative correlation with MD(all P<0.001). The combined diagnosis of mGCC, pRNFL thickness and MD had the highest efficiency in NVG(sensitivity: 79.00%, specificity: 87.00, AUC=0.973, 95%CI=0.956-0.990, P<0.05).CONCLUSION: The mGCC and thickness of pRNFL in patients with NVG had a negative correlation with MD. mGCC, pRNFL thickness and MD have a certain diagnostic value on NVG, and the efficiency of combined diagnosis is the highest.