BackgroundInsomnia， a common sleep disorder， is robustly associated with cardiovascular diseases， diabetes， and psychiatric disorders， substantially impairing quality of life. Although clinically commonly used medications are effective， long-term use may lead to drug resistance and dependence. While the efficacy of Ganmai Dazao Decoction in improving insomnia is definite， its underlying molecular mechanisms remain unclear. ObjectiveTo explore the active ingredients and core targets of Ganmai Dazao Decoction in the treatment of insomnia， systematically reveal its potential molecular pharmacological mechanism， and to provide references for clinical application. MethodsIn November 2024， the active ingredients and related targets of Ganmai Dazao Decoction were screened from the INPUT database. Insomnia-related datasets were acquired from the Gene Expression Omnibus （GEO） database， followed by differential expression analysis using GEO2R to identify differentially expressed genes （DEGs） associated with insomnia. The shared targets were obtained through Venn diagrams， and the protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape 3.9.1. Enrichment analyses were conducted on the shared targets using Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG）. The top 3 key active ingredients and the top 10 core targets in terms of node degree values were selected. Molecular docking and molecular dynamics simulation of receptors and ligands were performed using AutoDock 4.4.6， and the results were visualized using Pymol 3.0.3 to further verify the stability of the receptor-ligand complex system. ResultsA total of 337 active ingredients and 5 265 drug-related targets in Ganmai Dazao Decoction were retrieved， along with 1 061 insomnia-related DEGs. 287 shared targets were identified between Ganmai Dazao Decoction and insomnia. The traditional Chinese medicine-active ingredients-shared targets-disease network showed that quercetin， catechins and kaempferol were the key components of Ganmai Dazao Decoction in treating insomnia. These three components alleviate insomnia by acting on ten core targets， including nuclear factor kappa B inhibitor alpha （NFKBIA）， fibronectin 1 （FN1）， interleukin-6 （IL6）， protein c-Fos （FOS）， histone acetyltransferase p300 （EP300）， histone deacetylase 1 （HDAC1）， transcription factor Jun （JUN）， heat shock protein HSP 90-alpha 1 （HSP90AA1）， glyceraldehyde 3-phosphate dehydrogenase （GAPDH）， and interleukin-1 beta （IL1β）. GO and KEGG enrichment analyses indicated that Ganmai Dazao Decoction may alleviate insomnia through the IL17 signaling pathways， lipid and atherosclerosis signaling pathways， and other mechanisms. The results of molecular docking demonstrated strong binding affinity between the 3 key components and the 10 core targets of Ganmai Dazao Decoction. Molecular dynamics simulations further confirmed the stability of the quercetin-GAPDH， catechin-HDAC1 and kaempferol-EP300 complexes. ConclusionThe key components of Ganmai Dazao Decoction， namely quercetin， catechin， and kaempferol， exert therapeutic effects on insomnia by targeting 10 core proteins and modulating multiple pathways， including the IL17 signaling pathway， lipids and atherosclerotic-related pathways. ［Funded by Chengdu Medical College Level Scientific Research Project （number， CYZYB23-01）］

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Masking is an important tool to evaluate auditory function,but it has always posed challenges in clinical audiology tests.This is mainly because of the lack of in-depth research into the biological mechanisms of masking over a long period,and an insufficient understanding of the principles of masking generation.This article describes the neurobiological fundamentals of clinical audiology test masking in terms of altered resonance patterns in the basilar membrane,the two-tone suppression effect of cochlear outer hair cell receptor potentials,the loss of bal-ance between excitatory and inhibitory transmitters at dopamine receptors,and disturbances in the phenomenon of phase-locking of nerve discharges.Overmasking is due to an enhanced contralateral inhibitory effect on cochlear out-er hair cell motility.This article aims to provide further guidance for clinical audiologist or physician in the proper use of masking.

Masking is an important tool to evaluate auditory function,but it has always posed challenges in clinical audiology tests.This is mainly because of the lack of in-depth research into the biological mechanisms of masking over a long period,and an insufficient understanding of the principles of masking generation.This article describes the neurobiological fundamentals of clinical audiology test masking in terms of altered resonance patterns in the basilar membrane,the two-tone suppression effect of cochlear outer hair cell receptor potentials,the loss of bal-ance between excitatory and inhibitory transmitters at dopamine receptors,and disturbances in the phenomenon of phase-locking of nerve discharges.Overmasking is due to an enhanced contralateral inhibitory effect on cochlear out-er hair cell motility.This article aims to provide further guidance for clinical audiologist or physician in the proper use of masking.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

OBJECTIVE To investigate the prognostic value of pre-treatment serum lactate dehydrogenase(LDH)levels in patients with locally recurrent nasopharyngeal carcinoma(NPC)treated with salvage intensity-modulated radiotherapy(IMRT)and to determine its association with rT staging.METHODS The records of 97 patients with locally relapsed and non-metastatic NPC who received salvage IMRT treatment in our center from January 2018 to April 2022 were collected,including 51 patients who died,18 patients with distant metastases,30 patients with local failure,and 67 patients with prognostic adverse events(death,distant tumors/local metastases).Clinical data,local failure-free survival(LFFS),distant metastasis-free survival(DMFS)and overall survival(OS)were obtained from all patients,and the relationship between LDH and the prognosis of salvage IMRT therapy in NPC patients was analyzed.RESULTS The serum LDH level before salvage IMRT was significantly higher in the death[221.25(178.24,339.13)U/L vs.124.82(79.0,159.50)U/L,Z=-5.122],local failure[230.75(170.89,394.50)U/L vs.157.85(91.78,216.95)U/L,Z=-3.442],distant metastasis[261.62(153.55,465.50)U/L vs.168.98(101.75,237.75)U/L,Z=-2.478]and poor prognosis group[220.05(167.20,506.16)U/L vs.93.45(69.95,154.35)U/L,Z=-6.018],and all P<0.05.Serum LDH levels were divided into dichotomous variables according to median values(≥177.50 U/L vs.<177.50 U/L),the Cox univariate model found that the hazard ratios of LDH affecting LFFS,DMFS,OS and toxic-related death(TRD)were 3.759(1.660-8.558),4.217(1.383-12.861),3.226(1.715-6.069),3.363(1.750-6.463),P<0.05.LDH remained an independent prognostic factor for LFFS,DMFS,OS,and TRD in multivariate regression analysis(P<0.05).Compared with patients with LDH<177.50 U/L,more patients in the LDH≥177.50 U/L group had local progression-related death,and the no LFFS stage,no DMFS stage and OS were shorter in the LDH≥177.50 U/L group(log rank=11.624,7.559,14.758),P<0.05.In predicting overall survival,adding LDH to the rT stage is preferable to the rT stage alone.CONCLUSION LDH is an important factor in predicting LFFS,DMFS,OS,and TRD after saving IMRT in patients with locally relapsed,non-metastatic NPC,and the value of LDH combined with rT staging in predicting overall survival is high.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

OBJECTIVE To develop a magnetic resonance(MRI) imaging radiomics and clinical factor model to predict recurrence and metastasis in patients with primary stage Ⅱ-Ⅳa nasopharyngeal carcinoma(NPC) and to validate its predictive effect on adjuvant chemotherapy(AC) outcomes. METHODS A retrospective analysis was performed on 135 patients with stage Ⅱ to Ⅳa NPC diagnosed in Longgang Otolaryngology Hospital of Shenzhen City from February 2018 to October 2021. After receiving standard synchronous radiotherapy and chemotherapy at our hospital,some patients received induction chemotherapy and/or AC based on cisplatin/nedaplatin. The imaging features of enhanced MRI sequences were extracted using PyRadiomics platform. Using the least absolute shrinkage and selection operator(LASSO) algorithm to filter features associated with recurrence or metastasis,a clinical radiomics model(CRM) was constructed by Cox multivariate analysis in a training cohort and validated in a validation cohort. All patients were divided into high-risk and low-risk groups based on the model's median Rad score. Kaplan-Meier survival curves were used to compare 3-year recurrence or metastasis free survival(RMFS) in patients with AC in high-risk group and low risk-group. RESULTS A total of 960 imaging features were extracted. The CRM consists of 9 features(6 imaging features and 3 clinical factors). In the training cohort,the area under the CRM curve(AUC) of 3-year RMFS was 0.867(P<0.001),and the sensitivity and specificity were 90.32％ and 79.66％,respectively. In the validation cohort,the AUC was 0.836(P<0.001) and the sensitivity and specificity were 100.0％ and 71.43％,respectively. The 3-year RMFS in high-risk and low-risk groups was 42.86％(27/63) and 94.44％(68/72)(log rank=50.818,P<0.001),respectively. Among CRM high-risk patients,3-year RMFS was significantly better in patients who received AC than those who did not(log rank=6.204,P=0.013). CONCLUSION CRM based on 3 clinical factors and 6 MRI features provides a non-invasive method for predicting the prognosis of NPC,which may help guide treatment decisions for clinical adjuvant chemotherapy,but further external verification is needed.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of combination of infrared thermography (IRT) and high frequency colour Doppler ultrasound (HFCDU) in location of superficial fascia perforating vessels and to guide the design and harvest of super-thin anterolateral thigh flap (ALTF) .Methods:A total of 15 patients who received medical treatment in the Department of Orthopaedics, Zhoushan Hospital and Department of Foot and Ankle Surgery, Wuxi No.9 People’s Hospital from January 2022 to July 2023 were selected to participate the study. The patients were 11 males and 4 females, aged 26 to 64 years with an average age of 48.3 years. A total of 14 wounds of foot, 1 of hand, 1 of forearm and 1 of ankle were reconstructed with 17 free super-thin ALTFs. The sizes of soft tissue defect were 5 cm×3 cm-23 cm×7 cm. The flaps were 6 cm×4 cm to 25 cm×8 cm in size. The donor sites were directly pulled together and sutured. Before surgery, HFCDU was applied to locate the perforator vessels across deep fascia into superficial fascia of the ALTF. IRT was further employed to locate the superficial perforator vessels on the superficial fascia in operating room. The running course of a perforating branch in the superficial fascia was determined by the running courses of the perforating branch located by the two location methods. Super-thin ALTFs were harvested and the precise locations of the perforating vessels were verified in surgery. SPSS 23.0 software was used for data analysis. Rank sum test was performed on the location data of superficial fascial perforating branches found by IRT and the data in surgery. P<0.05 was considered a statistically significant difference. All patients were included in the postoperative follow-up by means of visit of outpatient clinic and via WeChat reviews, where the survival and functional recovery of the flaps were observed. Results:A total of 30 perforating vessels had been located by HFCDU and 30 by IRT, and a total of 31 perforating vessels were found in superficial fascia in surgery. The true positive rate was 93.3%, with a false positive rate at 6.7% and a false negative rate at 9.7%. The rank sum test calculated P=0.853 for the number of perforating vessels located by the IRT and those found from surgery. There was no significant difference between the 2 detecting methods. No postoperative complication occurred in all 14 flaps. Partial necrosis occurred in 1 flap but healed after dressing changes. Venous occlusion had occurred in 1 flap, it was rectified after surgical exploration. Superficial infection happened in 1 flap and it was improved after anti-infection treatment. Postoperative follow-up was conducted for 3-12 months. The flaps were in good texture with satisfactory appearance and function of limbs. All donor sites healed well without scar hyperplasia. Conclusion:IRT combined with HFCDU is a reliable method in location of perforator vessels of ALTF, and it is an ideal technique in the exploration of perforator vessels and in the harvest of a super-thin flap.