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

Objective To assess the efficacy of a novel inguinal tourniquet in healthy individuals and to investigate the relationship between localized inguinal compression and femoral artery blood flow occlusion.Methods A self-controlled study was conducted.From November 9 to November 30,2024,11 volunteers were recruited at the Third Medical Center of Chinese PLA General Hospital.Three compression methods--finger pressure,a novel groin tourniquet,and a SAM junction tourniquet(SJT)—were applied bilaterally to the inguinal region until distal blood flow signals disappeared.Each compression method was tested in 22 trials with a 5-minute interval between operations.Differences in hemostatic efficacy between bilateral inguinal regions and across compression methods were compared.Subsequently,the novel tourniquet was incrementally pressurized in 120 mmHg multiples using an integrated pressure device to analyze trends in popliteal artery blood flow velocity.Observational indicators included the internal pressure of the tourniquet pressurization device,peak systolic velocity(PSV)of popliteal artery,inguinal surface pressure magnitude,inguinal surface pressure distribution,and pain scores(assessed using a single-dimensional numerical rating scale).Results No statistically significant difference was observed in the minimum pressure required to occlude femoral artery blood flow bilaterally(P>0.05).The success rates of femoral artery blood flow occlusion at the inguinal region were 100%for the novel inguinal tourniquet,SJT,and finger pressure.The novel inguinal tourniquet induced the highest pain scores,ranging from 5 to 8.A significant reduction in PSV of popliteal artery was noted when the intra-tourniquet pressure reached 360 mmHg and 480 mmHg(P<0.05),with a 95%hemostasis efficacy observed within the range of 360-600 mmHg.No significant association was observed between the recovery of popliteal artery blood flow after limb movement and inguinal pressure distribution(P>0.05).The PSV of popliteal artery exhibited the strongest negative correlation with the average pressure within the inguinal compression area(r=-0.79,P<0.001),with a linear regression fitting line of y=69.69-0.13x(P<0.001,R2=0.58).Conclusions The novel inguinal tourniquet effectively occludes femoral artery blood flow within a pressure range of 360-600 mmHg,accompanied by moderate-to-severe pain.Its hemostatic mechanism mainly relies on increasing the mean pressure within the inguinal compression area.

Objective:To explore the effect of empagliflozin combined with levosimendan on plasma levels of type Ⅰcollagen(Collagen Ⅰ),connective tissue growth factor(CTGF),and α-smooth muscle actin(α-SMA)in patients with coronary heart disease(CHD)and heart failure(HF).Methods:This randomized controlled study enrolled 106 CHD+HF patients admitted to Linfen Central Hospital between June 2022 and June 2023.Patients were divid-ed into control group(n=53,treated with levosimendan)and combined treatment group(n=53,received addition-al empagliflozin).Both groups were treated for 12 weeks.The total effective rate,exercise endurance,cardiac function,levels of HF biomarkers,inflammatory factors,myocardial fibrosis indexes and incidence of adverse reac-tions were compared between two groups.Results:The total effective rate of combined treatment group was signif-icantly higher than that in the control group(94.34％vs.81.13％,P＜0.001).Compared with patients in the con-trol group,those in the combined treatment group had significant higher cardiac output(CO)[(4.62±0.89)L/min vs.(3.90±0.75)L/min],left ventricular ejection fraction(LVEF)[(55.42±6.09)％vs.(48.97±5.74)％]and 6-minute walking distance(6MWD)[(405.69±56.47)m vs.(295.65±41.32)m](P＜0.001 all),and signifi-cant lower levels of N-terminal pro B-type natriuretic peptide(NT-proBNP)[(192.06±29.02)pg/ml vs.(313.58±20.98)pg/ml],soluble suppression of tumorigenicity 2(sST2)[(53.33±5.79)μg/L vs.(60.04±6.88)μg/L],interleukin-1β(IL-1β)[(18.16±5.42)ng/L vs.(21.07±6.31)ng/L],high-sensitive C-reactive protein(hsCRP)[(1.69±0.41)mg/L vs.(1.98±0.56)mg/L],tumor necrosis factor α(TNF-α)[(0.87±0.26)ng/L vs.(1.19±0.32)ng/L],Collagen Ⅰ[(162.58±30.55)μg/L vs.(189.98±41.32)μg/L],CTGF[(114.26±14.89)μg/L vs.(125.87±19.47)μg/L]andα-SMA[(90.63±19.57)μg/L vs.(101.39±23.62)μg/L](P＜0.05 or＜0.01).There was no significant difference in the incidence of adverse reactions between two groups(15.09％vs.16.98％,P=0.791).Conclusion:Empagliflozin combined with levosimendan has a significant therapeutic effect in patients with coronary heart disease and heart failure,which calld significantly improve cardiac function,exercise endurance,reduce levels of heart failure biomarkers and inflammatory factors,and inhibit myo-cardial fibrosis.

Objective:To investigate the association of Chinese visceral adiposity index (CVAI) with arterial stiffness progression.Methods:This study was a prospective cohort study, which included participants who completed at least 1 measurement of brachial-ankle pulse wave velocity (baPWV) between 2010 and 2016, with complete physical examination data during the same period, and completed baPWV measurement during follow-up. The time of completing the first baPWV measurement was defined as the baseline. All participants were divided into 4 groups according to quartiles of baseline CVAI (<60.84, 60.84-89.67, 89.68-117.45,≥117.46). The baPWV progression was calculated (baPWV progression=(baPWV follow-up-baPWV baseline)/duration of follow-up). We assessed the association of CVAI groups with baPWV progression using multivariate linear regression models. Results:A total of 17 261 participants were included. Of these, the age was (47.6±11.6) years, and 11 285 (65.38%) were males. The results of multivariate linear regression models showed that compared with the CVAI<60.84 group, the baPWV at baseline increased by 39.62 cm/s (95% CI 28.57-50.67, P<0.01) in the 60.84-89.67 group, 76.37 cm/s (95% CI 64.71-88.04, P<0.01) in the 89.68-117.45 group, and 92.83 cm/s (95% CI 80.53-105.14, P<0.01) in the≥117.46 group. The median follow-up time was 2.49 years. Compared with the CVAI<60.84 group, annual change of baPWV progression increased by 17.17 cm/s (95% CI 10.36-23.97, P<0.01) in the 60.84-89.67 group, 24.59 cm/s (95% CI 17.38-31.80, P<0.01) in the 89.68-117.45 group, and 25.75 cm/s (95% CI 18.13-33.36, P<0.01) in the ≥117.46 group. Conclusion:Higher CVAI is closely associated with the progression of arterial stiffness, and the arterial stiffness progression accelerates with increased CVAI.

Receptor Protein Tyrosine Phosphatases(RPTPs)are a class of membrane proteins that play a crucial role in cellular signal transduction,primarily responsible for regulating the level of protein tyrosine phosphorylation within cells.They participate in various biological processes such as cell proliferation,differentiation,migration,and apoptosis.As a key group of signal transduction regulators,RPTPs are involved in multiple signaling pathways in the nervous system,such as regulating neuronal development,dendritic and axonal growth,and synapse formation.These functions are crucial for the normal development and maintenance of the nervous system.Studies have shown that RPTPs are involved in the occurrence and development of various neuropsychiatric disorders,such as bipolar disorder,autism,schizophrenia,and restless leg syndrome,and are considered potential therapeutic targets.Several studies are exploring how to regulate their expression and function.Here we review the studies of RPTPs in the nervous system,including their roles in axon guidance,synapse formation,and neuropsychiatric disorders,which helps to understand the functions of RPTPs and provides a basis for finding new therapeutic targets for neuropsychiatric diseases.

Objective To evaluate the efficacy and safety of magnetic resonance-guided modified ligation of the intersphincteric fistula tract in the treatment of deep anorectal abscess.Methods A retrospective study was conducted on 148 patients with deep anorectal abscess treated at our hospital from September 2019 to June 2023,who met the inclusion criteria.Of these,51 patients in the observation group underwent modified LIFT,while 97 patients in the control group received incision and drainage.Using propensity score matching,47 patients from each group with balanced baseline characteristics were selected,resulting in a total of 94 patients being included in the analysis.The study compared operation time,hospital stay,pain index,postoperative complications,anal function,and healing rate between the two groups.Results Primary lesions originating in the sphincter space were identified through preoperative magnetic resonance imaging in all 94 patients.The mean operation time for the observation group was(43.75±11.77)minutes,significantly longer than that of the control group at(28.90±8.67)minutes(P<0.05).At three months post-surgery,the healing rate in the observation group was 80.9%,which was signifi-cantly higher than the 57.4%observed in the control group(P<0.05).Among patients with fistulas in the observation group,the healing rate was 73.1%,although this difference was not statistically significant in the univariate analysis of clinical characteristics(P>0.05).No significant differences were found between the two groups regarding the length of hospital stay,pain index,postoperative complications,or anal function(all P>0.05).Conclusions Modified LIFT guided by MRI can be conditionally applied in the treatment of deep anorectal abscesses.This approach can enhance the initial surgical healing rate without significantly increasing the incidence of postoperative complications,thereby avoiding potential damage to anal function.

Aim To determine the effects of Shengjiang Powder on gastric mucosal injury and ex-plore its mechanisms.Methods A bibliometric study was conducted to understand the current research status of Shengjiang Powder.The main pharmacological com-ponents of Shengjiang Powder were obtained using liq-uid chromatography-mass spectrometry(LC-MS),and mechanisms were predicted through network pharma-cology analysis.Sprague-Dawley Rats with gastric mu-cosal injury were treated with Vatacoenayme and differ-ent doses of Shengjiang Powder by intragastric adminis-tration.Gastric tissues were collected and stained with HE to observe morphological changes.ELISA was used to detect the levels of TNF-α and IL-1β in serum.IHC was used to evaluate the expression of MUC5AC and MUC6 in the gastric mucosa.Results Bibliometric a-nalysis indicated that Shengjiang Powder is widely used in the treatment of various internal and external inju-ries.LC-MS identified the top 20 compounds as the main pharmacological components of Shengjiang Pow-der,yielding 525 target compounds,of which 129 o-verlapped with gastritis-related targets.GO analysis i-dentified 2,127 entries,and KEGG analysis identified 140 pathways,suggesting that Shengjiang Powder might improve gastric mucosal injury through multiple targets and pathways.HE staining results demonstrated that Shengjiang Powder could significantly improve gas-tric mucosal inflammation in rats.ELISA results showed that Shengjiang Powder effectively reduced the levels of TNF-α and IL-1 β in rat serum.IHC results indicated that Shengjiang Powder effectively downregu-lated MUC5AC expression and upregulated MUC6 ex-pression.Conclusion Shengjiang Powder can im-prove gastric mucosal injury by alleviating inflammation and regulating the surface mucus barrier.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

The contents of the female inguinal hernia include abdominal organs such as ovaries and fallopian tubes, and most of these are the result of sliding hernias. However, it is worth noting for surgeons specialized in hernia and abdominal wall surgery that there is a rare clinical diagnosis of hernia uterine inguinale, which is commonly seen in the Müllerian anomaly. Combined with relevant research progress at home and abroad, as well as the clinical experience in the diagnosis and treatment of patients with inguinal uterine hernia caused by Müllerian duct anomaly, the authors systematically introduce the clinical manifes-tations, key diagnosis and treatment points of female Müllerian duct anomaly in the inguinal region.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.