ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Background Type 2 diabetes mellitus is one of the most prevalent diseases,which imposes a heavy burden on patients' families and the society.Sleep disorders are recognized as risk factors for the development of diabetes,which may affect the onset and development of diabetes through neuro-endocrino-metabolic pathways,so identifying the factors responsible for the sleep quality of diabetic patients is of great importance in improving their sleep quality.Objective To investigate the relationship among fear of disease progression,executive function and sleep quality in patients with type 2 diabetes mellitus,so as to provide references for improvement of sleep quality in patients with type 2 diabetes mellitus.Methods A sample of 197 patients with type 2 diabetes mellitus who were admitted to the Endocrinology Department of the Second Affiliated Hospital of the Air Force Military Medical University from January to May 2023 and met the criteria defined in the Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China(2020 edition)were consecutively selected.All subjects were assessed using Fear of Progression Questionnaire-Short Form(FoP-Q-SF),Behavior Rating Inventory of Executive Function-Adult version(BRIEF-A)and Pittsburgh Sleep Quality Index(PSQI).Then the Process macro for SPSS(Model 4)and Bootstrap technique were applied to examine the mediating effect of executive function on the relationship between fear of disease progression and sleep quality in patients with type 2 diabetes mellitus.Results ①75 patients(38.07%)with type 2 diabetes mellitus were found to have sleep problems.②PSQI score in patients with type 2 diabetes mellitus was positively correlated with FoP-Q-SF score and BRIEF-A score(r=0.159,0.287,P<0.01).③Executive function mediated the relationship between fear of disease progression and sleep quality,the indirect value was 0.076(95%CI:0.022～0.146),accounting for 39.58%of the total effect.Conclusion Sleep disorders are common in patients with type 2 diabetes mellitus,and executive function may play a medicating role in the relationship between fear of disease progression and sleep quality.

In the study of cardiovascular diseases,Peroxiredoxin 6(PRDX6)is the only mammalian 1-Cys member of the Peroxiredoxin(PRDX)family and has attracted much attention.PRDX6 plays a unique role in oxidative stress due to its peroxidase activity and phospholipase A2 activity,and has been shown to participate in redox homeostasis and phos-pholipid metabolism.In recent years,the role of PRDX6 in the occurrence and development of cardiovascular diseases has received great attention.However,there is no unified understanding of the function of PRDX6 in the cardiovascular system at present.This article aims to briefly summarize the research progress of PRDX6 in cardiovascular diseases such as atherosclerosis,pulmonary hypertension,myocardial infarction,heart failure,abdominal aortic aneurysm,and systemat-ically review the expression changes,mechanism of action,and possible therapeutic potential of PRDX6 in these cardiovas-cular diseases,hoping to provide new ideas and strategies for cardiovascular diseases intervention.

Gastric cancer is one of the most com-mon malignant tumors in the digestive system,which often occurs in middle-aged and elderly peo-ple.Traditional Chinese medicine recognizes gastric cancer as a kind of tumor characterized by fluid de-ficiency,heat accumulation and the growing bind-ing of toxins in the stomach.It is commonly treated with heat-clearing and detoxifying drugs in clinical practice.Hedyotis diffusa-Scutellaria barbata herb pair(HS)has the effects of clearing heat and detoxi-fying,promoting blood circulation,resolving car-buncle and expulsing boil,anti-inflammatory and analgesic,which are consistent with the etiology and pathogenesis of gastric cancer,therefore,it can be used for the treatment of gastric cancer.Modern pharmacological researches have con-firmed that HS can play an anti-gastric cancer role by inducing cell apoptosis,inhibiting cell prolifera-tion,inhibiting angiogenesis,improving immune mi-croenvironment and down-regulating telomerase activity.Herein,this review summarizes the active ingredients and related mechanism responsible for the anti-gastric cancer effect of HS,which will pro-vide the theoretical basis for its clinical use and the development of new drugs against gastric cancers.

Objective:To investigate the effect of the transcription factor TBX1 on the proliferation of colorectal cancer cells and to explore potential molecular mechanisms.Methods:The mRNA and protein levels of TBX1 in colorectal cancer cell lines HCT116, RKO, SW480, HT29, and LOVO were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Colorectal cancer cell lines HCT116 and SW480 cells with low TBX1 expression were transfected with either a pcDNA3.1 plasmid containing TBX1 mimics (TBX1 overexpression group) or an empty pcDNA3.1 plasmid (the control group). LOVO cells with high TBX1 expression were transfected with small interfering RNA (siRNA) targeting TBX1 including si-TBX1-8604A, si-TBX1-8604B, and a negative control siRNA (si-NC), which were treated as si-TBX1-8604A group, si-TBX1-8604B group, and si-NC group. qRT-PCR was used to detect the expressions of transcriptional level TBX1 and PARK2, and Western blot was used to detect the protein levels of TBX1, PARK2, and key factors in the MAPK and PI3K signaling pathways. Methyl Thiazolyl Tetrazolium (MTT) assay and cell colony formation assay were used to detect the cell proliferation. Combining literatures and the JASPAR database, 2 binding sites of TBX1 in the PARK2 promoter region were predicted. Chromatin immunoprecipitation assay was employed to verify the binding sites of TBX1 to PARK2 in HCT116 and SW480 cells. Dual luciferase reporter gene assay was used to verify the targeting relationship between TBX1 and PARK2. The expression of TBX1 and PARK2 in colon cancer tissues was analyzed by using the Cancer Genome Atlas (TCGA) database (September 2023).Results:High TBX1 expression in HCT116 and SW480 cells transfected with TBX1 mimics plasmid was confirmed by qRT-PCR and Western blot, while TBX1 expression was successfully knocked down in LOVO cells transfected with siRNA targeting TBX1. MTT assay indicated that the absorbance values for HCT116 cells in TBX1 overexpression group on d1, d3, d5, and d7 after inoculation, and for SW480 cells on d3, d5, and d7 after inoculation were lower than those in the control group, and the differences were statistically significant (all P < 0.01). LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group exhibited higher absorbance values than the si-NC group on d1, d3, d5, and d7 after inoculation, and the differences were statistically significant (all P < 0.05). Cell colony formation assay revealed that after 14 d, the colony number of HCT116 cells [(387±9) vs. (843±13)] and SW480 cells [(413±9) vs. (931±15)] in TBX1 overexpression group was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The colony number of LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group was (493±77) and (470±32), respectively, which was higher than that in the si-NC group (349±26), and the differences were statistically significant (all P < 0.05). The protein relative expression levels of p-ERK and p-AKT S473 in HCT116 and SW480 cells in TBX1 overexpression group were lower than those in the control group, while protein relative expression levels of p-ERK and p-AKT S473 in LOVO cells in the si-TBX1-8604A group and si-TBX1-8604B group were higher than those in the si-NC group, and the differences were statistically significant (all P < 0.05). The relative expression level of PARK2 mRNA in HCT116 and SW480 cells (all P < 0.01) and the protein level in the overexpression group were higher than those in the control group. Chromatin immunoprecipitation assay demonstrated that the enrichment times of TBX1 binding to 2 sites of PARK2 intron in HCT116 and SW480 cells in TBX1 overexpression group were higher than that in the control group, and the differences were statistically significant (all P < 0.05). Dual luciferase reporter gene assay showed that the relative luciferase activity of HCT116 and SW480 cells co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and pGL3 plasmid containing PARK2 mimics was higher than that of cells co-transfected with empty pcDNA3.1 and pGL3 plasmids, co-transfected with empty pcDNA3.1 plasmid and pGL3 plasmid containing PARK2 mimics, co-transfected with pcDNA3.1 plasmid containing TBX1 mimics and empty pGL3 plasmid, and the differences were statistically significant (all P < 0.05). Spearman analysis showed that there was a positive correlation between transcriptional level TBX1 and PARK2 in colon cancer tissues (288 cases) in TCGA database ( r = 0.226, P < 0.001); and the relative expression level of PARK2 mRNA in colon cancer tissues (383 cases) was lower than that in normal intestinal tissues (50 cases), and the difference was statistically significant ( P < 0.001). Conclusions:Elevated expression of transcriptional factor TBX1 inhibits the proliferation of colorectal cancer cells, potentially by activating the downstream target gene PARK2 and inhibiting the phosphorylation of ERK and AKT in the MAPK and PI3K signaling pathways, ultimately affecting the activation of these pathways.

As one of the standard electrophysiological signals in the human body, the photoplethysmography contains detailed information about the blood microcirculation and has been commonly used in various medical scenarios, where the accurate detection of the pulse waveform and quantification of its morphological characteristics are essential steps. In this paper, a modular pulse wave preprocessing and analysis system is developed based on the principles of design patterns. The system designs each part of the preprocessing and analysis process as independent functional modules to be compatible and reusable. In addition, the detection process of the pulse waveform is improved, and a new waveform detection algorithm composed of screening-checking-deciding is proposed. It is verified that the algorithm has a practical design for each module, high accuracy of waveform recognition and high anti-interference capability. The modular pulse wave preprocessing and analysis software system developed in this paper can meet the individual preprocessing requirements for various pulse wave application studies under different platforms. The proposed novel algorithm with high accuracy also provides a new idea for the pulse wave analysis process.
Humans ; Systems Analysis ; Algorithms ; Software ; Heart Rate ; Microcirculation

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).