Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal disorder driven by multiple factors including genetics, immunity, and environment, and is clinically classified into ulcerative colitis and Crohn's disease. Currently, mice and zebrafish are the primary experimental animals used in IBD research, among which zebrafish have emerged as an ideal model due to their unique advantages. Compared with rodent models, zebrafish serve as an effective and convenient model, offering advantages such as a short life cycle, robust reproductive capacity, small size, and transparent embryos. These characteristics make zebrafish highly suitable for dynamic tracking of continuous pathological progression and high-throughput drug screening. Zebrafish share over 70% genetic homology with humans, and their intestinal cellular composition and ontogeny closely resemble those of humans. Moreover, the structure and characteristics of their gut microbiota are similar to the human intestinal microbiome, providing a solid foundation for studying the relationship between gut microbiota and IBD. With advances in biotechnology, zebrafish IBD models generated by chemical induction or genetic engineering can accurately simulate the core pathological features of human IBD, such as intestinal wall thickening, inflammatory cell infiltration, and elevated expression of pro-inflammatory factors. These models have played a significant role in revealing the pathogenesis of IBD as well as the development of targeted therapeutic drugs. This article first outlines the intestinal characteristics of zebrafish and features of zebrafish IBD models, then provides an in-depth analysis of their application in IBD pathogenesis research from multiple aspects, including genetics, immunity, environment and diet, and infection. It also reviews research progress on the application of zebrafish in the development of anti-inflammatory drugs, probiotics, and traditional Chinese medicine therapies, aiming to provide researchers with references for the rational use of zebrafish models at all stages of preclinical research, to advance fundamental IBD research and accelerate breakthroughs in this field.

Objective: To investigate the relationship of metabolic score for insulin resistance (METS-IR) with bone mineral content (BMC) and bone metabolic markers levels among adolescents, so as to provide a scientific foundation for the early identification and prevention of bone related diseases. Methods: From 2017 to 2019 and 2023, a total of 1 414 adolescents aged 12-18 years from Yinchuan were selected using a method combining convenient sampling with stratified cluster random sampling. The data of basic information, body mass index, BMC, serum osteocalcin (OC), type I collagen cross linked C-terminal peptide (CTX) and calcium (Ca), METS-IR among adolescents were obtained by questionnaire survey, physical measurement and laboratory examination,and METS-IR was divided into four groups Q1-Q 4 according to P 25 , P 50 and P 75 . Logistic regression models combined with restricted cubic splines were employed to analyze the relationship between METS-IR and low BMC as well as low bone metabolic markers. The receiver operating characteristic (ROC) curve was used to evaluate METS-IR effectiveness in diagnosing low BMC. Results: The levels of BMC, OC, CTX, Ca and METS-IR in the surveyed adolescents were (2.66±0.52)kg, (20.49±13.77) ng/mL , (2 460.89±1 818.96)pg/mL, (2.47±0.67)mmol/L, 30.63±7.58. After adjusting for gender, age and physical activity level, METS-IR in Q 4 group had a reduced risk of low BMC and low CTX [ OR (95% CI )=0.03(0.01-0.07), 0.45(0.32-0.65)] and an elevated risk of low OC [ OR (95%CI )=1.85(1.28-2.67)], compared with the Q 1 group (all P <0.05). Gender stratified analyses revealed similar trends for both males and females (all P <0.05). Non linear dose response relationships were observed between METS-IR and low BMC ( P total trend <0.01, P non linearity =0.01), as well as low OC ( P total trend <0.01, P non linearity =0.01), while a linear relationship was detected with low CTX ( P total trend <0.01, P non linearity =0.72). ROC curves revealed that METS-IR had the best diagnostic performance for low BMC (AUC=0.85, 95% CI=0.82-0.88, P <0.01). Conclusions Higher METS-IR score is linked to reduced risk of low BMC and CTX but increase risk of low OC among adolescents. These findings suggest METS-IR is a reliable indicator for assessing BMC and early predicting bone health risk among adolescents.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

OBJECTIVE To establish fingerprints and multi-components determination of Jieze lotion, and use chemometrics methods for quality evaluation. METHODS The HPLC-DAD fingerprints was established and 10 components were recognized by comparison with references. Meanwhile, their contents were determined. The data were evaluated by the methods of chemometrics such as similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. RESULTS The similarity of 11 batches of Jieze lotion were all >0.95. The linearity was good(r≥0. 999 1) and the average recoveries were between 89.70% and 106.0% with the RSD of 1.52%−3.41%. Instrument precision, stability and reproducibility of the method were all great. The contents of the common ten components(gallic acid, protocatechuic acid, neochlorogenic acid, caftaricacid, 5-O-feruloylquinicacid, chlorogenic acid, phellodendrine chloride, magnoflorine, 4-O-feruloylquinic acid, berberinehydrochloride) were 40.103−55.841, 2.347−6.179, 8.336−23.810, 7.084−21.956, 33.098−53.833, 24.597−49.610, 21.587−31.188, 5.915−13.162, 115.381−189.702, 31.378−112.686 μg·mL−1, respectively. The results of chemometrics showed that the 11 batches of samples could be divided into 4 categories, and the strong characteristic peaks used to distinguish each batch of samples were berberine hydrochloride, 4-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid and 5-O-feruloylquinic acid. CONCLUSION The method is accurate and reliable, and it can be used for the quality control and comprehensive evaluation of Jieze lotion.

Objective:To evaluate the clinical diagnostic significance of altered functional connectivity (FC) within the central executive network (CEN) in patients with mild cognitive impairment (MCI) related to end-stage renal disease (ESRD).Methods:A total of 155 patients with ESRD receiving hemodialysis treatment at the department of nephrology, Changzhou Second People's Hospital, from June 2020 to December 2023, were recruited. According to wether the patient had MCI symptoms, 85 patients were classified in the ESRD with MCI group, while 70 patients were in the ESRD without MCI group. Additionally, 76 healthy volunteers matched for age, sex, and years of education were enrolled in the study. All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal cognitive assessment. With the dorsolateral prefrontal cortex serving the core of CEN, functional attributes of the CEN were calculated using seed-based FC analysis. Based on these imaging features and clinical data, a LASSO + Logistic regression model was constructed to predict MCI in patients with ESRD, and SPSS 20.0 software was used for analysis.Results:There were significant differences in FC in 10 brain regions, including the inferior temporal gyrus, temporal pole, corpus callosum, ventromedial prefrontal cortex, ventral posterior cingulate cortex, inferior parietal lobule, precuneus, dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and supplementary motor area, among the three groups (all P<0.001). Post hoc analysis revealed that the zFC values of the ventromedial prefrontal cortex and dorsomedial prefrontal cortex in ESRD with MCI group(0.385±0.219, 0.215±0.247) were significantly higher than those in the ESRD without MCI group (0.278±0.184, 0.121±0.221) and the healthy controls (0.206±0.217, 0.078±0.212) (all P<0.05). In addition to the ventromedial prefrontal cortex and dorsomedial prefrontal cortex, zFC values in all brain regions exhibiting significant differences were markedly reduced in both the ESRD with MCI group (temporal pole (0.157±0.221 vs 0.327±0.191), corpus callosum (0.100±0.184 vs 0.327±0.191), ventral posterior cingulate cortex (0.027±0.199 vs 0.128±0.154), inferior parietal lobule (0.218±0.195 vs 0.387±0.213), precuneus (0.193±0.184 vs 0.358±0.142), supplementary motor area (0.182±0.163 vs 0.231±0.163)) and the ESRD without MCI group (inferior temporal gyrus (0.055±0.125 vs 0.250±0.146), temporal pole (0.048±0.223 vs 0.335±0.195), corpus callosum (0.192±0.161 vs 0.327±0.191), inferior parietal lobule (0.234±0.197 vs 0.387±0.213), dorsal anterior cingulate cortex (0.383±0.242 vs 0.585±0.195), supplementary motor area (0.076±0.162 vs 0.231±0.163)), compared to healthy controls ( P<0.01). The zFC values of 4 brain regions in ESRD with MCI group were significantly higher than those in the ESRD without MCI group (inferior temporal gyrus (0.226±0.205 vs 0.055±0.125), temporal pole (0.157±0.221 vs 0.048±0.223), dorsal anterior cingulate cortex (0.498±0.254 vs 0.383±0.242), supplementary motor area (0.182±0.163 vs 0.076±0.162)) ( P<0.05). The diagnostic model developed from these results demonstrated excellent discrimination(the area under the curve=0.94, the sensitivity=0.89, the specificity=0.86, and the accuracy=0.88). Additionally, it exhibited strong calibration ( R2=0.908) and clinical applicability(patients benefited when the predicted probability exceeded 0.12). Conclusion:The enhancement of FC in CEN and its attenuation with other networks provide relevant evidence for the neuropathological mechanisms underlying MCI in patients with ESRD.The diagnostic model based on FC changes in the CEN, as presented in this study, is valuable for detecting early cognitive impairment in patients with ESRD.

Objective To investigate the effect of Yiqi Jiedu Recipe(YQ)on the proliferation,migration,and invasion of nasopharyngeal carcinoma cells,and to explore its mechanisms of action on proliferation,migration,and invasion through the TGF-β1/SMAD3 signaling pathway.Methods(1)The 5-8F cells were divided into four groups:solvent control group,YQ 0.5 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and 5-fluorouracil 2 μg·mL-1 group.Cell proliferation was monitored using real-time cell analysis(RTCA).Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using the Western Blot method.(2)The 5-8F cells were divided into five groups:solvent control group,TGF-β1 10 ng·mL-1 group,TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and LY3200882 10 μmol·L-1 group.Cell proliferation was monitored using RTCA.Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using Western Blot.(3)The nude mice were randomly assigned into the model group,YQ group,and 5-fluorouracil group.Subcutaneous injection of 5-8F cell suspension was performed to establish the xenograft nude mouse model of nasopharyngeal carcinoma.After the tumors reached a certain size,the 5-fluorouracil group received intraperitoneal injection of 5-Fu once every 2 days,while the other groups were orally administered corresponding drugs once a day for three consecutive weeks.Tumor volume was measured every 3 days.Western Blot was conducted to assess the protein expression levels of β-catenin,E-cadherin,and N-cadherin in the tissues of each group.Results Compared with the solvent control group,the proliferation curves of 5-8F cells in the YQ(0.5 mg·mL-1,1.0 mg·mL-1)groups showed a decrease.The migration and invasion abilities of the cells were both reduced(P＜0.05,P＜0.01).Additionally,the expression of E-cadherin protein significantly increased(P＜0.01),while the protein expression of β-catenin,N-cadherin,TGF-β1,and SMAD3 all decreased(P＜0.05,P＜0.01).Compared with the model group,the transplanted tumor volume of nasopharyngeal carcinoma in the YQ group significantly decreased(P＜0.05).Furthermore,the protein expression of β-catenin and N-cadherin in the transplanted tissues of the YQ group was significantly downregulated(P＜0.05,P＜0.01),while the expression of E-cadherin protein was significantly upregulated(P＜0.01).After the addition of the activator and inhibitor of TGF-β1 signaling pathway,compared with the YQ 1.0 mg·mL-1 group,the TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group showed a significant increase in the expression of TGF-β1,SMAD3,β-catenin,and N-cadherin proteins(P＜0.05,P＜0.01)and obvious enhancement of the abilities of cell proliferation,migration,and invasion(P＜0.01).Conclusion Yiqi Jiedu Recipe can inhibit the proliferation,migration,and invasion by regulating the TGF-β1/SMAD3 signaling pathway.

Neurotrophic keratopathy (NK) is a relatively rare degenerative corneal disease.Over time, it can cause varying degrees of ocular surface damage, leading to corneal ulcers, perforations and even blindness.The best opportunity to reverse ocular surface damage is in the earliest stage of NK.However, patients experience few typical symptoms and diagnosis is often delayed.In 2021, BMC Ophthalmology published the Expert Consensus on the Identification, Diagnosis and Treatment of Neurotrophic Keratopathy in Volume 21.Through the interpretation of the consensus, this paper hopes to further improve ophthalmologists' understanding of the screening and treatment of NK, and optimize the management norms of NK diagnosis and treatment.

Objective:The current study aims to explore the factors related to the efficacy of cognitive behavior therapy for insomnia (CBT-I) from the perspective of patients and to provide references for more effective implementation of CBT-I.Methods:Using qualitative research methods, 21 insomnia patients with depression/anxiety were treated with CBT-I for 8 consecutive times. Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD 17), and Hamilton Anxiety Scale (HAMA) were assessed at baseline and the end of the 8th week of treatment. The paired sample t-test was conducted. Semi-structured interviews were performed at week 2, week 4, and week 8 respectively and thematic analysis was used to code and analyze the interview data. Results:Compared with baseline data, the symptoms of insomnia (13.6±2.0 vs. 6.9±2.4), depression (14.6±5.5 vs. 5.0±3.6), and anxiety (17.2±3.4 vs. 5.3±3.9) were significantly improved after 8 weeks of CBT-I treatment ( t=-3.31, -3.19, -2.94, all P<0.01). The patient factors influencing the efficacy of CBT-I were treatment expectation and approval, motivation, compliance, and internalization of treatment content. The therapist factors were professionalism, well-directed, treatment style, supervision, and giving hope. Conclusion:Compliance and high levels of participation of the patients can benefit the treatment efficacy of CBT-I. Therapists should have sufficient experience, stimulate patients′ motivation, improve patients′ compliance, and carry out adequate psychological education in the early stage to increase the efficacy of CBT-I.