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

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

BACKGROUND: Mild cognitive impairment (MCI) is common in atrial fibrillation (AF) patients and may develop earlier in those with multiple cardiovascular comorbidities, potentially impairing self-management and treatment adherence. This study aimed to characterize the prevalence and profile of MCI in AF patients, examine its associations with cardiovascular comorbidities, and assess how these comorbidities influence specific cognitive domains. METHODS: This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021. Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment. Associations between comorbidities and MCI were assessed by logistic regression, and cognitive domains were compared using the Mann-Whitney U test. RESULTS: Of 4136 AF patients (mean age: 64.7 ± 9.4 years, 64.7% male), 33.5% of patients had MCI. Among the AF patients, 31.2% of patients had coronary artery disease, 20.1% of patients had heart failure, and 18.1% of patients had hypertension. 88.7% of patients had left atrial enlargement, and 11.0% of patients had reduced left ventricular ejection fraction. Independent factors associated with higher MCI prevalence included older age (OR = 1.04, 95% CI: 1.03-1.05, P < 0.001), lower education level (OR = 1.51, 95% CI: 1.31-1.73, P < 0.001), hypertension (OR = 1.28, 95% CI: 1.07-1.52, P = 0.001), heart failure (OR = 1.24, 95% CI: 1.04-1.48, P = 0.020), and lower left ventricular ejection fraction (OR = 1.43, 95% CI: 1.04-1.98, P = 0.028). A higher CHA₂DS₂-VASc score (OR = 1.27, 95% CI: 1.22-1.33, P < 0.001; ≥ 2 points vs. < 2 points), and greater atherosclerotic cardiovascular disease burden (OR = 1.45, 95% CI: 1.02-2.08, P = 0.040; 2 types vs. 0 type) were linked to increased MCI risk. These above factors influenced various cognitive domains. CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity. Patients with multiple comorbidities are at higher risk, highlighting the importance of routine cognitive assessment to support self-management and integrated care.

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

Objective To analyze the medication law and compatibility characteristics of TCM compounds for the treatment of myocardial infarction in the national patent database.Methods TCM compounds for treating myocardial infarction were retrieved from CNIPA patent publication website.A prescription database was built using Excel 2019 software to statistically analyze the frequency of medicinal use and their properties,taste and meridian tropism;SPSS Modeler 18.0 software was used to analyze the association rules of drugs;a network of Chinese materia medica co-occurrence was constructed using Cytoscape 3.10.0,and systematic clustering analysis was performed on the Chinese materia medica in the core network.Results A total of 146 patents of TCM compounds were included,involved 440 kinds of Chinese materia medica.High frequency drugs included Salviea Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Angelicae Sinensis Radix,Glycyrrhizae Radix et Rhizoma,etc.The main property was warm,the main tastes were bitter,sweet and pungent,and the medicines mostly belongs to the liver meridian,heart meridian and spleen meridians.Commonly used medicinal pairs included Angelicae Sinensis Radix-Chuanxiong Rhizoma,Astragali Radix-Salviea Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra-Angelicae Sinensis Radix,etc.Commonly used tripartite combinations included Paeoniae Radix Rubra-Chuanxiong Rhizoma-Angelicae Sinensis Radix,Carthami Flos-Angelicae Sinensis Radix-Chuanxiong Rhizoma,Carthami Flos-Chuanxiong Rhizoma-Angelicae Sinensis Radix,etc.Clustering analysis showed four types of combinations.Conclusion TCM compound patents for the treatment of myocardial infarction is based on promoting blood circulation,removing blood stasis,and relieving pain,while also using methods such as eliminating phlegm,tonifying qi,warming yang,and nourishing yin.It can provide references for clinical medication.

Schizophrenia is a common, severe, and complex psychiatric disorder worldwide. Genetic factors account for around 80% of the etiology of schizophrenia, yet objective diagnostic biomarkers remain lacking. This article reports two cases of female monozygotic twins diagnosed with schizophrenia, exhibiting a balanced translocation between 22q11.2 and 4p15.3. Reviewing the literature, we analyze and discuss the correlation between chromosomal balanced translocation regions and the pathogenesis of mental disorders. This aims to encourage psychiatrists to consider new perspectives on the diagnosis of schizophrenia.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 μg/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.

Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels， but their effectiveness is limited. The mechanisms underlying its onset are complex， and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression， involving multiple pathways， including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 （TLR4/NLRP3）， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， brain-derived neurotrophic factor/tyrosine kinase receptor B （BDNF/TrkB）， cyclic AMP/protein kinase A/cAMP response element-binding protein （cAMP/PKA/CREB）， and others. Traditional Chinese medicine（TCM） is based on a holistic approach and the principle of treatment based on the differentiation of syndromes， regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems， involving liver Qi stagnation， heart spirit deficiency， kidney essence depletion， and spleen dysfunction. TCM compound treatments focus on soothing the liver， strengthening the spleen， calming the heart， and replenishing essence， with formulas such as Xiaoyaosan， Zishui Qinggan Yin， and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi， such as salidroside， ginsenoside Rb₁， astragaloside， and muscone. External TCM treatments， primarily acupuncture， aim to open the orifices and invigorate the spirit. Acupoints such as Baihui， Shenting， and Yintang are commonly used. Additionally， massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression， aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.