To summarise the clinical experience of treating insomnia with the method of resolving depression， regulating the middle， and tranquilising mind. It is believed that the key to the pathogenesis of insomnia lies in qi depression， disharmony of qi pivot， and disharmony of qi and blood， and the core treatment is to resolve depression， regulating the middle， and tranquilising mind. The self-prescribed Jieyu Anmian Formula （解郁安眠方） could be used as the basic treatment， then modified according to the performance of the patient and syndromes. For syndrome of liver depression restricting spleen， the treatment should soothe liver and invigorate spleen， resolve depression and regulate the middle； for syndrome of liver depression and phlegm coagulation， the treatment should resolve depression and phlegm， support the earth and free the wood； for syndrome of liver depression transforming into fire， the treatment should soothe liver and clear fire， resolve depression and dysphoria； for syndrome of qi stagnation and blood stasis， the treatment should activate blood and regulate the middle， resolve depression and tranquilise mind.

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

OBJECTIVES: To explore the mechanism of Circ-MYOCD back-splicing and its regulatory role in myocardial hypertrophy. METHODS: Sanger sequencing and RNase R assays were performed to verify the circularity and stability of Circ-MYOCD, whose subcellular distribution was determined by nuclear-cytoplasmic fractionation. Bioinformatics analysis and mass spectrometry from pull-down assays were conducted to predict the RNA-binding proteins (RBPs) interacting with Circ-MYOCD. In rat cardiomyocytes H9C2 cells, the effects of HNRNPH1 and HNRNPL knockdown and overexpression on Circ-MYOCD back-splicing were evaluated. In a H9C2 cell model of angiotensin II (Ang II)-induced myocardial hypertrophy, the expression of HNRNPH1 was detected, the effects of HNRNPH1 knockdown and overexpression on progression of myocardial hypertrophy were assessed, and the regulatory effect of HNRNPH1 on Circ-MYOCD back-splicing was analyzed. RESULTS: Sanger sequencing confirmed that the junction primers could amplify the correct Circ-MYOCD sequence. RNase R and nuclear-cytoplasmic fractionation assays showed that Circ-MYOCD was stable and predominantly localized in the cytoplasm. Bioinformatics analysis and mass spectrometry from the Circ-MYOCD pull-down assay identified HNRNPH1 and HNRNPL as the RBPs interacting with Circ-MYOCD. In H9C2 cells, HNRNPH1 knockdown significantly enhanced while its overexpression inhibited Circ-MYOCD back-splicing; HNRNPH1 overexpression obviously increased the expressions of myocardial hypertrophy markers ANP and BNP, while its knockdown produced the opposite effect. In Ang II-induced H9C2 cells, which exhibited a significant increase of HNRNPH1 expression and increased expressions of ANP and BNP, HNRNPH1 knockdown obviously increased Circ-MYOCD expression, decreased MYOCD expression and lowered both ANP and BNP expressions. CONCLUSIONS HNRNPH1 regulates Circ-MYOCD back-splicing to influence the progression of myocardial hypertrophy.
Animals ; Rats ; RNA, Circular/genetics* ; Cardiomegaly/metabolism* ; Myocytes, Cardiac/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism* ; Cell Line ; RNA Splicing ; Angiotensin II ; RNA-Binding Proteins

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Atherosclerosis(AS)is the common pathological basis of ischemic cardiovascular diseases,and its formation mechanism is complex.Western medical treatment has problems such as a long cycle and a high relapse rate.Ethnic medicine is an important part of traditional medicine,which has unique efficacy in treating cardiovascular diseases.Studies have shown that the Mongolian medicine Eldon-Uriel regulates blood lipids and improves blood rheology in the treatment of AS.This paper aims to pro-vide new ideas for the prevention and treatment of AS by collecting,organizing,and summarizing the relevant literature on Eldon-Uriel and introducing its unique concept,mechanism of action,and clinical studies in the treatment of AS.

Age-related hearing loss(ARHL)is a common chronic disease that poses a serious threat to the physical and mental health of the elderly in an aging society.It is a sensorineural hearing loss characterized by the loss of auditory hair cells,stria vascularis lesions,apoptosis of spiral ganglia,and degeneration of the audi-tory central nervous system,reducing the quality of life of the patients.This article reviews the research progress in the relationship of ARHL with Alzheimer's disease,depression,and frailty,as well as the daily intervention in ARHL.This review aims to improve people's awareness and attention to the health hazards of ARHL and to delay the occurrence and development of ARHL by implementing daily intervention measures to form a healthy lifestyle.

Objective To observe the risk factors of ischemic mitral regurgitation(IMR)in ischemic cardiomyopathy.Methods Totally 143 patients with ischemic cardiomyopathy were retrospectively enrolled and divided into IMR+group(n=68)or IMR-group(n=75)based on IMR,while 50 healthy volunteers were taken as controls(control group).The general information,conventional ultrasonic parameters of left ventricle,three-dimensional speckle tracking imaging(3D-STI)parameters as well as mitral valve structural and functional parameters were compared among groups,and the risk factors of IMR were screened with logistic regression analysis.Results Significant differences of left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular global longitudinal strain(LVGLS),the peak systolic twist(Twist),tenting volume(VTent)and total leaflet area(TLA)/annulus area(AA)were found between IMR+group and IMR-group(all P＜0.05).Decreased LVGLS,decreased Twist and increased VTent were all independent risk factors of IMR in ischemic cardiomyopathy(all P＜0.05).Conclusion Decreased LVGLS,decreased Twist and increased VTent were independent risk factors of IMR in ischemic cardiomyopathy.

OBJECTIVE To observe the efficacy and safety of hydromorphone in patient-controlled intravenous analgesia(PCIA)after uvulopalatopharyngoplasty.METHODS A total of 90 patients who received uvulopalatopharyngoplasty in Central Theater General Hospital from January 2022 to June 2023 were selected and divided into three groups(n=30 in each group)by using random number table method.Control group was given sufentanil 2.0 μg/kg,group A was given hydromorphone 0.20 mg/kg and group B was given hydromorphone 0.30 mg/kg.The analgesic parameters of three groups were background infusion rate of 1.2 ml/h,PCA amount of 2 ml,and lock-up time of 10 min.VAS score and Ramsay sedation score at 2 h,6 h,12 h,24 h and 48 h after surgery were recorded,as well as the number of compressions within 48 h after surgery,and the incidence of adverse reactions were analyzed.RESULTS There were no significant differences in intraoperative blood loss,operation time and intraoperative urine volume among the three groups(P>0.05).VAS score in group A and group B at 2 h(2.0±0.3,2.2±0.4),6 h(1.8±0.4,1.9±0.4),12 h(1.8±0.4,1.7±0.4),24 h(1.6±0.3,1.5±0.4)and 48 h(1.1±0.3,1.2±0.4)were significantly lower than those in control group(2.8±0.5,2.3±0.5,2.1±0.4,2.0±0.5,1.7±0.5)(P<0.05),but there was no significant difference between group A and group B(P>0.05).The Ramsay score of group A and group B at 2 h,6 h,12 h,24 h,and 48 h after operation was significantly lower than that of the control group(P<0.05).There was no significant difference in Ramsay score between group A and group B(P>0.05).The total number of compressions and effective number of compressions in group A and group B at 12 h,24 h and 48 h after surgery were lower than those in control group(P<0.05),but there was no significant difference between group A and group B(P>0.05).The incidence of total adverse reactions in group B was higher than that in group A and control group(P<0.05).There was no significant difference in the incidence of total adverse reactions between group A and control group(P<0.05).CONCLUSION Hydromorphone can effectively be used for postoperative self-controlled analgesia in patients with uvulopalatopharyngoplasty,and the efficacy is better than sufentanil,but the dose of 0.20 mg/kg hydromorphone has better safety than that of 0.3 mg/kg hydromorphone.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.