The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

OBJECTIVE: To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultrasound (LIPUS) on erectile dysfunction (ED) caused by renal deficiency and phlegm-dampness syndrome. METHODS: One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine. The patients in control group were treated with Wenshen Chushi Decoction. While the patients in observation group were treated with Wenshen Chushi Decoction combined with LIPUS for 8 consecutive weeks. After the treatment, the efficacy was evaluated using the International Index of Erectile Function-5 (IIEF-5) score, Penile Flow Index (PFI), Traditional Chinese Medicine Syndrome Score, Self-Rating Depression Scale (SDS) score, and Self-Rating Anxiety Scale (SAS) score. Safety was also observed. And the efficacy was followed up 4 weeks after the end of treatment. RESULTS: Fifty-seven cases were enrolled into control group finally with 55 cases in the treatment group. After the treatment, all the patients in both of groups showed an improvement in IIEF-5 scores (P<0.01). Compared with the control group (19.09 ± 2.22), the IIEF-5 score in observation group (20.42 ± 2.39) increased significantly (P<0.01). After the treatment, the scores of PFI, TCM syndrome and SDS in both groups decreased (P<0.01, P<0.05, P<0.01). Compared with the control group (［3.77 ± 1.21］, ［9.91 ± 1.71］ and ［39.88 ± 2.63］ points), the observation group (［2.92 ± 1.08］, ［4.78 ± 1.45］, and ［34.51 ± 2.09］ points） showed a more significant decrease (P<0.01). There was no significant difference in total effective rate between the two groups (P>0.05). During follow-up, the IIEF-5 scores of both groups of patients were higher than those before (P<0.05, P<0.01), and the observation group score was higher than that in the control group (［17.15 ± 3.37］ vs ［13.63 ± 1.96］, P<0.01). No adverse reaction and abnormality of indicators occurred in both of two groups. CONCLUSION Wenshen Chushi Decoction has a significant therapeutic effect on ED caused by renal deficiency and phlegm-dampness syndrome. It can not only improve the quality of erection, but also improve the physical and mental symptoms associated with ED， which makes therapeutic effect lasting longer.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/etiology* ; Middle Aged ; Adult ; Treatment Outcome ; Medicine, Chinese Traditional ; Ultrasonic Therapy ; Phytotherapy

Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation. Memory retrieval, as the only representation of memory content and an active form of memory processing that induces memory reconsolidation, has attracted increasing attention in recent years. Although the molecular mechanisms specific to memory retrieval-induced reconsolidation have been gradually revealed, an understanding of the time-dependent regulatory mechanisms of this process is still lacking. In this study, we applied a transcriptome analysis of memory retrieval at different time points in the recent memory stage. Differential expression analysis and Short Time-series Expression Miner (STEM) depicting temporal gene expression patterns indicated that most differential gene expression occurred at 48 h, and the STEM cluster showing the greatest transcriptional upregulation at 48 h demonstrated the most significant difference. We then screened the differentially-expressed genes associated with that met the expression patterns of those cluster-identified genes that have been reported to be involved in learning and memory processes in addition to dipeptidyl peptidase 9 (DPP9). Further quantitative polymerase chain reaction verification and pharmacological intervention suggested that DPP9 is involved in 48-h fear memory retrieval and viral vector-mediated overexpression of DPP9 countered the 48-h retrieval-induced attenuation of fear memory. Taken together, our findings suggest that temporal gene expression patterns are induced by recent memory retrieval and provide hitherto undocumented evidence of the role of DPP9 in the retrieval-induced reconsolidation of fear memory.
Animals ; Fear/physiology* ; Male ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics* ; Memory Consolidation/physiology* ; Time Factors ; Mental Recall/drug effects* ; Mice ; Gene Expression Profiling

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Air Pollution/analysis* ; Environmental Exposure/analysis* ; China/epidemiology* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Monitoring

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective:To compare the short-term effect and adverse reaction of venetoclax(VEN)combined with azacitidine(AZA)versus"7+3"regimen in newly diagnosed elder patients with acute myeloid leukemia(AML).Methods:From January 2021 to January 2022,the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed,including VEN+AZA group(41 cases)and"7+3"group(38 cases).The propensity score matching(PSM)method was used to balance confounding factors,then response,overall survival(OS),progression-free survival(PFS)and adverse reactions between the two groups were compared.Results:The ORR of VEN+AZA group and"7+3"group was 68％and 84％,respectively,and the CRc was 64％and 72％,respectively,the differents were not statistically significant(P＞0.05).In the VEN+AZA group,there were 5 non-remission(NR)patients,4 with chromosome 7 abnormality(7q-/-7),and 1 with ETV6 gene mutation.Median followed-up time between the two groups was 8 months and 12 months,respectively,and the 6-months OS was 84％vs 92％(P=0.389),while 6-months PFS was 84％vs 92％(P=0.258).The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳmyelosuppression,and the incidence rate was not statistically different(P＞0.05).The median time of neutrophil recovery in two groups was 27(11-70)d,25(14-61)d(P=0.161),and platelet recovery was 27(11-75)d,25(16-50)d(P=0.270),respectively.The infection rate of VEN+AZA group was lower than that of"7+3"group(56％vs 88％,P=0.012).The rate of lung infections of two groups was 36％and 64％,respectively,the difference was statistically significant(P=0.048).Conclusion:The short-term effect of VEN+AZA group and"7+3"regimens in eldrly AML patients are similar,but the VEN+AZA regimen had a lower incidence of infection.The presence of chromosome 7 abnormality(7q-/-7)may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

Objective:To investigate the expression of kinase-like gene CT10 regulatory fac-tor(CRKL)in intrahepatic cholangiocarcinoma(ICC)and its effect on the proliferation and invasion of intrahepatic cholangiocarcinoma cells.Methods:qRT-PCR detected CRKL transcription in ICC pa-tient tissues and adjacent tissues.Immunohistochemistry assessed CRKL expression in ICC tissues and adjacent tissues,and analyzed its relationship with clinicopathological features.For the inhibition of CRKL expression in QBC939 cells by siRNA technology,the effect of CRKL silencing on AKT and ERK signaling pathway was measured by Western blot.CRKL's influence on QBC939 cell prolifera-tion and invasion was analyzed by MTT,clonogenesis,and Transwell assays.Results:The expres-sion of CRKL in ICC tissues was up-regulated,and there were statistically significant differences in CRKL expression in ICC with different clinicopathological features such as tumor size,lymph node metastasis and TNM stage.Cellular experiments showed a significant decrease in the phosphoryla-tion of AKT and ERK upon inhibition of CRKL,and the proliferation and invasion ability of ICC cells was significantly diminished(P＜0.05).Conclusion:CRKL promotes ICC cell proliferation and invasion through AKT and ERK pathways,offering new molecular targets and directions for targeted therapy.

Objective To explore the promoting effect of egg yolk oil combined with heat-clearing and detoxi-fying traditional Chinese medicine external washing on postoperative wound healing in patients with perianal abscesses based on growth factors in the wound granu-lation tissue.Methods Eighty patients with perianal abscesses admitted to our hospital from January 2023 to May 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.Three days after surgery,the control group received routine treatment,such as external washing with heat-clearing and detoxifying Chinese herbal medicine and dressing changes with vase-line gauze.The observation group received additional treatment with egg yolk oil,and both groups were treated continuously for 7 days.The clinical efficacy,improvement in clinical symptoms,and wound recovery at different time points;serum inflammatory cytokines;and expression levels of wound granulation tissue-related factors were compared between the two groups.Results The total effective rate was higher in the observation group than the control group(95%vs.75%,P<0.05).The time of pruritus disappearance,decaying flesh,emer-gence of new epithelium,and healing were shorter in the observation group than in the control group(P<0.05).The pain degree,wound secretion,granulation morphology and surrounding tissue edema score of the observation group were significantly decreased at 7 and 10 days after surgery compared with the control group(P<0.05).Serum levels of interleukin(IL)-1β,IL-8,and tumor necrosis factor-α were lower in the observation group than the control group at 7 and 10 days after surgery(P<0.05).The levels of basic fibroblast growth factor,vascular endothelial cell growth factor,and transforming growth factor-βin wound granulation tissue were higher in the observation group than the control group at 7 and 10 days after surgery(P<0.05).Conclusion The external application of egg yolk oil combined with heat-clearing and detoxifying Chinese herbs can significantly improve the clinical symptoms of patients with perianal abscesses and promote wound healing,with significant therapeutic effects.This may be related to the inhibition of inflammatory cytokine expression and the promotion of wound granulation tissue growth factor expression.