Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.

Objective To investigate the effects of different use methods of tourniquet on hidden blood loss and knee joint swelling in total knee arthroplasty(TKA),and to explore its potential benefits for postoperative rehabilitation.Methods A prospective study was conducted from March 2018 to March 2023 in Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University,involving 131 patients who underwent TKA.The patients were divided into three groups based on the method of tourniquet use:44 patients routinely used a tourniquet in group A,48 patients only used a tourniquet during the application of bone cement in group B,and 39 patients did not use tourniquet in group C.Operation time,dressing changes,intraoperative blood loss,total blood loss,explicit blood loss,hidden blood loss,percentage of hidden blood loss,postoperative blood transfusion,hemoglobin(Hb),hematocrit(HCT),C-reactive protein(CRP),and creatine kinase(CK)were compared among groups.The pain and functional recovery were evaluated by visual analogue scale(VAS)and knee society clinical rating system(KSS)before surgery,and 3 days,1 month,and 3 months after surgery.The degree of limb swelling and the range of motion of the knee were also compared among groups.Results Group A had shorter operation time and less frequency of postoperative dressing changes than the other two groups(P<0.05).The hidden blood loss and total blood loss in group A were significantly less than those in group C(P<0.05),and the hidden blood loss and total blood loss volume in the three groups from low to high was group A

Objective To investigate the effect of bone metastasis on the efficacy of immune check-point inhibitors(ICI)in treatment of advanced non-small cell lung cancer(NSCLC).Methods A retro-spective analysis was conducted in 248 patients with advanced NSCLC who received ICI therapy.The patients were divided into bone metastasis group(110 cases)and non-bone metastasis group(138 ca-ses)based on the presence of bone metastasis.Clinical characteristics,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.The correlations of factors such as bone metastasis with the survival prognosis of NSCLC patients were analyzed using the Cox proportional hazards regression mod-el.A total of 60 treatment-naive NSCLC patients with bone metastasis were selected from research ob-jects,with 30 patients receiving ICI combined with conventional chemotherapy(combination group)and 30 patients receiving conventional chemotherapy alone(chemotherapy group).The therapeutic effects and incidence of treatment emergent adverse events(TEAE)were compared between the two groups.Results There were no statistically significant differences in ORR and DCR between the bone metastasis and non-bone metastasis groups(P＞0.05).The PFS of the bone metastasis group(5.53 months)was shorter than that of the non-bone metastasis group(7.72 months)(x2=3.674,P=0.045).However,there was no statistically significant difference in OS between the bone me-tastasis group and the non-bone metastasis group(16.98 versus 17.56 months,x2=1.333,P=0.248).Multivariate Cox regression analysis showed that bone metastasis was an independent prog-nostic factor for PFS in NSCLC patients(HR=1.52,95％CI,1.10 to 1.98,P=0.003),but not a prognostic factor for OS(P＞0.05).The ORR and DCR in the combination group were 43.33％and 93.33％,respectively,which were higher than 26.67％and 76.67％in the chemotherapy group(P＜0.05).The PFS in the combination group was longer than that in the chemotherapy group(x2=4.023,P=0.036).However,there was no statistically significant difference in OS be-tween the two groups(x2=1.235,P=0.267).There were no statistically significant differences in the overall incidence of TEAEs or the incidence of≥grade 3 TEAE between the two groups(P＞0.05).Conclusion Although the occurrence of bone metastasis has an adverse effect on the effica-cy of ICI therapy in advanced NSCLC,patients with bone metastasis can still achieve better thera-peutic effects through ICI combined with chemotherapy compared with chemotherapy alone.

ObjectiveTo observe the distribution of traditional Chinese medicine （TCM） syndrome types in advanced pancreatic cancer patients， and explore the association between median survival time and different TCM syndromes and different intervention times of Chinese herbal medicine （CHM）. MethodsThe clinical data of 136 advanced pancreatic cancer patients who have received CHM for more than 3 months were collected retrospectively， including gender， age， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， western medicine treatment methods， TCM diagnosis and treatment information， and survival time. The Kaplan-Meier （KM） estimator was used， and the median survival time of patients was calculated. The TCM syndrome type of each patient was judged， and the main single syndrome types and compound syndrome types were summarized. The median survival time was compared among different compound syndrome types. The patients were further divided into the group of those having received CHM ≥6 months and those having received CHM ＜6 months. Whether receiving CHM ≥6 months was taken as the grouping variable， while the matching variables were age， gender， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， surgery， chemotherapy， and radiotherapy when propensity score matching was performed， and the difference in median survival time between the two groups of patients before and after matching was compared. ResultsFor 136 cases of advanced pancreatic cancer， the top five single syndromes were spleen qi deficiency， liver blood stasis， liver qi stagnation， spleen dampness， and liver heat. The main compound types were liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， liver constraint， qi stagnation and spleen deficiency syndrome， spleen-stomach yang deficiency and blood stasis syndrome， and spleen deficiency and dampness-heat internal accumulation syndrome. The overall median survival time before and after matching was 12.47 （7.70，17.10） months and 13.77 （8.83，17.20） months， respectively， and was significantly higher in the group treated with CHM ≥ 6 months than that treated with CHM ＜6 months （P＜0.05）. Among the 136 patients before matching， the median survival time of patients with spleen deficiency and dampness-heat internal accumulation syndrome was longest ［16.23 （14.17，19.40） months］， while that of patients with spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［7.33 （5.80，12.83） months］. For patients with liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， and spleen-stomach yang deficiency and blood stasis syndrome， those having received CHM ≥ 6 months have much longer median survival time than those having received CHM ＜6 months （P＜0.05）. Among the 108 patients after matching， the median survival time of those with spleen deficiency and dampness-heat internal accumulation syndrome was the longest ［15.23 （7.67，18.27） months］， while that of spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［8.80 （6.90，16.17） months］. For patients with liver-gallbladder dampness-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome， the median survival time was higher in the group treated with CHM ≥ 6 months treated with CHM ＜6 months （P＜0.05）. ConclusionAfter treatment with CHM， advanced pancreatic cancer patients with spleen deficiency and damp-heat internal accumulation had a better prognosis， while those with spleen-stomach yang deficiency and blood stasis had a worse prognosis. Treatment with CHM ≥ 6 months could extend the median survival of advanced pancreatic cancer patients with liver-gallbladder damp-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome.

Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

Objective To analyze the status quo and influencing factors of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy,to establish a risk prediction model,and to conduct internal validation of the model.Methods This study was a prospective nested case-control study.The patients with liver cancer undergoing chemotherapy for maintenance of totally implantable access port in a tertiary hospital in Shaanxi from October 2021 to September 2023 were selected as the investigation subjects.Patients with extubation due to complications were selected as an extubation due to complications group,and patients with planned extubation were randomly selected as a planned extubation group according to the matching number of 1∶10.Univariate analysis and Logistic regression analysis were used to explore the influencing factors of extubation due to complications.A visual nomogram risk prediction model was established,and the model was internally verified by receiver operating characteristic(ROC)curve,calibration curve and Hosmer-Lemeshow fit test.Results The incidence of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy was 7.0％.Infection(36.7％)and thrombosis(30.0％)were the main causes of extubation due to complications.BMI,TNM staging,diabetes,the number of catheter lumens in the access port and the chemotherapy times were the main influencing factors of extubation due to complications(P＜0.05).The area under ROC curve of the prediction model was 0.871;the best cut-off value was 0.106;the sensitivity was 0.800;the specificity was 0.820.The average absolute error between the actual and predicted values of the calibration curve was 0.011,and the calibration curve was close to the ideal curve.The Hosmer-Lemeshow goodness of fit test was x2=2.913(P=0.940).Conclusion The incidence of extubation due to complications of totally implantable access port in patients with liver cancer undergoing chemotherapy is low,and infection and thrombosis are the main reasons.Patients with a BMI≥ 24,TNM stage Ⅲ or Ⅳ,diabetes,double catheter lumens in the access port,and chemotherapy times＞5 were at higher risk of extubation due to complications.The risk prediction model developed in this study demonstrates good predictive accuracy,and it can serve as a valuable tool for healthcare professionals in early identification of patients at risk for extubation due to complications.

Objective:To evaluate the clinical efficacy and safety of hematoporphyrin monomethyl ether (HMME) -mediated photodynamic therapy (PDT) in the treatment of facial port-wine stains (PWS) in children with Sturge-Weber syndrome (SWS) .Methods:A retrospective analysis was conducted based on the clinical data from SWS children treated with HMME-PDT at the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from December 2020 to January 2022. HMME was intravenously injected at a dose of 5 mg/kg, followed by the irradiation of SWS lesions with a 532-nm light-emitting diode light source, and the treatment interval was 8 weeks. The efficacy of HMME-PDT for SWS was evaluated based on the subsidence of erythema and changes in the number and density of blood vessels under a dermoscope before and after treatment; adverse events after treatment were recorded. Fisher's exact test was used to analyze differences in efficacy.Results:A total of 15 children with SWS were included, comprising 7 males and 8 females, with an average age of 4.74 years (range, 1 - 14 years). There were 10 cases of clinical phenotype Ⅰ and 5 cases of type Ⅱ; 10 patients were accompanied by glaucoma, 6 by epilepsy, and 10 showed abnormalities on craniocerebral imaging. After HMME-PDT treatment, 4 out of 15 patients achieved complete remission of SWS lesions, 3 showed marked improvement, and 5 achieved improvement. Among 8 cases receiving 2 sessions of treatment, 1 achieved marked improvement and 4 showed improvement; among 7 cases receiving 3 or more sessions of treatment, 4 achieved complete remission, 2 achieved marked improvement, and 1 showed improvement; the proportions of patients achieving complete remission and marked improvement were significantly higher among those receiving 3 or more sessions of treatment than those receiving 2 sessions (both P < 0.05). Among 7 patients with pink-type PWS, 1 recovered completely, 2 achieved marked improvement, and 4 showed improvement; among 4 patients with purplish-red-type PWS, 3 recovered completely and 1 showed marked improvement; among 4 patients with thickened-type PWS, 1 achieved improvement; there was a significant difference in the proportions of patients achieving marked improvement or improvement among the patients with different types of PWS (both P < 0.05). Among 14 patients with lesions involving the central face region, 4 achieved marked improvement and 2 showed improvement; among 15 with lesions involving the lateral face region, 5 recovered completely, 3 achieved marked improvement, and 4 showed improvement; the recovery rate of lesions was higher in the lateral face region than in the central face region ( P < 0.05). Under a dermoscope, the skin lesions showed 4 vascular patterns: short rod-shaped vessels in 3 cases, linear vessels in 4, reticular vessels in 5, and mixed-type vessels in 3. The 3 patients with short rod-shaped vessels all recovered completely; among the 4 patients with linear vessels, 2 achieved marked improvement, and 2 showed improvement; among the 5 patients with reticular vessels, 1 recovered completely, 1 achieved marked improvement, and 3 showed improvement; the 3 patients with mixed-type vessels all showed poor response to the treatment; the proportions of patients who recovered completely and those who achieved improvement significantly differed among the patients with 4 different vascular patterns (both P < 0.05). All the children experienced varying degrees of pain, swelling, purpura, and crusting after treatment, but none exhibited exacerbation of ocular or neurological complications. Conclusion:HMME-PDT was safe and effective in the treatment of PWS in children with SWS, and its efficacy was related to the number of treatment sessions, lesion types and locations.

Objective To investigate the application of bronchoscope for children(BF-XP290)in diagnosing and treating peripheral pulmonary lesions(PPL)in adults.Methods Bronchoscope for children(BF-XP290)was used to diagnose and treat PPL.Results BF-XP290 could diagnose and treat PPL in direct view,and other techniques could overcome its shortcomings.Conclusion Bronchoscope for children(BF-XP290)can partially replace radial endobronchial ultra-sound(R-EBUS)in diagnosing and treating PPL in adults,reducing the investment of medical equipment,and is worthy of clinical promotion.

Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.