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.

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

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

OBJECTIVE Aimd to investigate the prevalence of olfactory dysfunction among healthy elderly individuals in China using a large sample size and to explore its correlations with demographic and other factors.METHODS A total of 5 258 participants who aged 60 and above underwent the T&T olfactometer test and completed questionnaires.The prevalence of olfactory dysfunction was reported,and logistic regression analyses were performed to assess the associations between olfactory dysfunction and other factors.RESULTS The overall prevalence of olfactory dysfunction in the study was 26.5%.Independent risk factors for olfactory dysfunction included advanced age,rural residence(OR=1.88,95%CI:1.60-2.22,P<0.01),current smoking(OR=1.45,95%CI:1.15-1.83,P<0.01),and self-reported olfactory dysfunction(OR=10.12,95%CI:8.44-12.14,P<0.01).In contrast,female gender(OR=0.70,95%CI:0.58-0.85,P<0.01)and high educational attainment were independently associated with a lower prevalence of olfactory dysfunction.CONCLUSION The prevalence of olfactory dysfunction among individuals aged 60 and above increased with age.Male gender,rural residence,low educational attainment,current smoking,and self-reported decline in olfactory function were independently associated with olfactory dysfunction.

Objective To observe the value of three-dimensional speckle tracking imaging(3D-STI)in evaluation on right ventricle(RV)function for predicting adverse events in patients with unstable angina(UA)after percutaneous coronary intervention(PCI).Methods A total of 155 UA patients who underwent both 3D-STI and conventional echocardiography and planned to accept PCI were prospectively enrolled and divided into adverse event group(n=37)and control group(n=118)based on the occurrence of adverse events after PCI or not.Clinical data and echocardiographic parameters were compared between groups,and new binary variables were generated according to the optimal cut-off values showed by the maximum Youden index of receiver operating characteristic curves of 3D-STI parameters being statistically different between groups.Then the independent predictors of adverse events among UA patients after PCI were analyzed,a combined model was constructed,and its predictive value was assessed.Results In adverse event group,the left ventricular end diastolic volume(LVEDV)was higher,while the left ventricular ejection fraction(LVEF),right ventricular free wall longitudinal strain(RVFWLS)and right ventricular global longitudinal strain(RVGLS)were all lower than those in control group(all P＜0.05).The optimal cut-off values for distinguishing adverse event or not was 110 ml for LVEDV,19.05%for RVFWLS and 19.75%for RVGLS,respectively,and all the 3 generated binary variables were independent predictors for adverse events of UA patients after PCI(all P＜0.05).The area under the curve of combined model for predicting adverse events in UA patients after PCI was 0.864.Conclusion RVFWLS＜19.05%and RVGLS＜19.75%obtained with 3D-STI,as well as LVEDV＞110 ml with conventional echocardiography were all independent predictors of adverse events in UA patients after PCI.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.

Objective To observe the value of three-dimensional speckle tracking imaging(3D-STI)in evaluation on right ventricle(RV)function for predicting adverse events in patients with unstable angina(UA)after percutaneous coronary intervention(PCI).Methods A total of 155 UA patients who underwent both 3D-STI and conventional echocardiography and planned to accept PCI were prospectively enrolled and divided into adverse event group(n=37)and control group(n=118)based on the occurrence of adverse events after PCI or not.Clinical data and echocardiographic parameters were compared between groups,and new binary variables were generated according to the optimal cut-off values showed by the maximum Youden index of receiver operating characteristic curves of 3D-STI parameters being statistically different between groups.Then the independent predictors of adverse events among UA patients after PCI were analyzed,a combined model was constructed,and its predictive value was assessed.Results In adverse event group,the left ventricular end diastolic volume(LVEDV)was higher,while the left ventricular ejection fraction(LVEF),right ventricular free wall longitudinal strain(RVFWLS)and right ventricular global longitudinal strain(RVGLS)were all lower than those in control group(all P＜0.05).The optimal cut-off values for distinguishing adverse event or not was 110 ml for LVEDV,19.05%for RVFWLS and 19.75%for RVGLS,respectively,and all the 3 generated binary variables were independent predictors for adverse events of UA patients after PCI(all P＜0.05).The area under the curve of combined model for predicting adverse events in UA patients after PCI was 0.864.Conclusion RVFWLS＜19.05%and RVGLS＜19.75%obtained with 3D-STI,as well as LVEDV＞110 ml with conventional echocardiography were all independent predictors of adverse events in UA patients after PCI.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.