Objective Most patients with chronic insomnia depend on long-term medication， which may easily lead to a poor treatment outcome and adverse drug reactions， and transcranial alternating current stimulation （tACS）， as a noninvasive neuromodulation technique， can improve chronic insomnia. This study aims to investigate the clinical efficacy of tACS combined with pharmacotherapy in the treatment of chronic insomnia. Methods A total of 46 patients with chronic insomnia were enrolled and randomly divided into pharmacotherapy group with 20 patients and pharmacotherapy+tACS treatment group with 26 patients. The tACS electrodes were attached to the frontal region and the bilateral mastoids， with a frequency of 77.5 Hz and a current intensity of 15 mA， for 40 minutes each time， once a day for 10 consecutive days. The primary outcome measures were Pittsburgh Sleep Quality Index （PSQI） score and its improvement rate after 4 weeks， and the secondary outcome measures included the scores of Hamilton Depression Rating Scale （HAMD）， Hamilton Anxiety Rating Scale （HAMA）， Mini-Mental State Examination （MMSE）， and Montreal Cognitive Assessment （MoCA） and their improvement rates. Results Compared with the pharmacotherapy group， the pharmacotherapy+tACS treatment group had a significant reduction in PSQI score （P<0.05）， with an improvement rate of 37% and 21%， respectively， suggesting that the combined therapy had a better effect in improving sleep quality. The pharmacotherapy+tACS treatment group also had reductions in HAMA and HAMD scores， suggesting improvements in anxiety and depression symptoms， and there were no significant differences in MMSE and MoCA scores between the two groups. Conclusion Pharmacotherapy combined with tACS has a better effect than pharmacotherapy alone in improving sleep quality and anxiety and depression symptoms in patients with chronic insomnia， and therefore， it has good application prospects in clinical practice.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

Cardiovascular diseases(CVD)are chronic disease with high morbidity and mortality in the world.Pinellia ternatais a traditional Chi-nese medicinal herb and has the effects on drying dampness,resolving phlegm,lowering symptoms,stopping vomiting and relieving swelling.In recent years,researches showed that Pinellia ternataand its active ingredients(β-sitosterol,baicalin,baica-lein,quercetin)had significant effects in the treat-ment of cardiovascular diseases.This review sum-marized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardio-vascular diseases,which provided a theoretical ba-sis for its clinical application.

Objective To screen and analyze key genes in rabbit corneal alkali burns based on transcriptomics se-quencing technology and bioinformatics techniques.Methods Thirty healthy male New Zealand rabbits were randomly di-vided into 2 groups(n=15 per group):The control group received no intervention,while the alkali burn group underwent corneal alkali burn modeling.Histological evaluation of corneal tissues was performed via hematoxylin-eosin(HE)stai-ning.Transcriptome sequencing was conducted for library construction and sequencing.Differentially expressed genes(DEGs)were identified using DESeq2,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway analysis.A protein-protein interaction(PPI)network was constructed to screen hub genes,and RT-PCR was employed to validate mRNA expression levels of key genes.Results HE staining revealed orderly arranged corneal stromal layers and scattered stromal cells in the control group,whereas the alkali burn group exhibited stromal edema,thickened collagen fibers with loose/disorganized alignment,and increased fibroblast and inflammatory cell infiltration.Compared to the control group,1 827 significant DEGs were identified in the alkali burn group,including 1 495 upregulated and 332 downregulated genes.GO analysis showed biological processes such as immune response,plasma membrane,and identical protein binding.KEGG analysis indicated that DEGs were enriched in pathways related to cancer,lipid and atherosclerosis,and neuroactive ligand-receptor interaction.The PPI network screened 11 key genes:neutrophil cytosolic factor 1(NCF1),neutrophil cytosolic factor 2(NCF2),matrix metallopeptidase 2(MMP2),ma-trix metallopeptidase 9(MMP9),interleukin-1α(IL-1α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(CXCL8),cluster of differentiation 4(CD4),C-C motif ligand 2(CCL2)and tumor necrosis factor(TNF).RT-PCR valida-tion revealed that the mRNA expression levels of key genes in the corneal tissues of the alkali burn group were significantly higher than those in the control group(all P＜0.05),consistent with the transcriptomic sequencing results.Conclusion Based on the rabbit corneal alkali burn model,this study identified 11 key genes(NCF1,NCF2,MMP2,MMP9,IL-1α,IL-1β,IL-6,CXCL8,CD4,CCL2 and TNF)through transcriptomics and bioinformatics analysis.

Objective To screen and analyze key genes in rabbit corneal alkali burns based on transcriptomics se-quencing technology and bioinformatics techniques.Methods Thirty healthy male New Zealand rabbits were randomly di-vided into 2 groups(n=15 per group):The control group received no intervention,while the alkali burn group underwent corneal alkali burn modeling.Histological evaluation of corneal tissues was performed via hematoxylin-eosin(HE)stai-ning.Transcriptome sequencing was conducted for library construction and sequencing.Differentially expressed genes(DEGs)were identified using DESeq2,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway analysis.A protein-protein interaction(PPI)network was constructed to screen hub genes,and RT-PCR was employed to validate mRNA expression levels of key genes.Results HE staining revealed orderly arranged corneal stromal layers and scattered stromal cells in the control group,whereas the alkali burn group exhibited stromal edema,thickened collagen fibers with loose/disorganized alignment,and increased fibroblast and inflammatory cell infiltration.Compared to the control group,1 827 significant DEGs were identified in the alkali burn group,including 1 495 upregulated and 332 downregulated genes.GO analysis showed biological processes such as immune response,plasma membrane,and identical protein binding.KEGG analysis indicated that DEGs were enriched in pathways related to cancer,lipid and atherosclerosis,and neuroactive ligand-receptor interaction.The PPI network screened 11 key genes:neutrophil cytosolic factor 1(NCF1),neutrophil cytosolic factor 2(NCF2),matrix metallopeptidase 2(MMP2),ma-trix metallopeptidase 9(MMP9),interleukin-1α(IL-1α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(CXCL8),cluster of differentiation 4(CD4),C-C motif ligand 2(CCL2)and tumor necrosis factor(TNF).RT-PCR valida-tion revealed that the mRNA expression levels of key genes in the corneal tissues of the alkali burn group were significantly higher than those in the control group(all P＜0.05),consistent with the transcriptomic sequencing results.Conclusion Based on the rabbit corneal alkali burn model,this study identified 11 key genes(NCF1,NCF2,MMP2,MMP9,IL-1α,IL-1β,IL-6,CXCL8,CD4,CCL2 and TNF)through transcriptomics and bioinformatics analysis.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Guided by the emphasis on learning process, the educational reform has designed a "trinity" comprehensive evaluation system (quantitative clinical practice, in-class medical record analysis, and staged comprehensive written test) as the formative evaluation of the course. Through this assessment system, students' self-learning potential is stimulated, clinical skills practice is strengthened, and "taking exams to promote learning and taking exams to promote teaching" is realized. In the practice of teaching reform, it has been found that compared with the conventional teaching class, the students in the teaching reform class have higher participation and are more satisfied with the process assessment of the "trinity" comprehensive evaluation system.