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

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To establish a method for simultaneous determination of 14 components in Cinnamomi Cortex;To comprehensively evaluate its quality by multivariate statistical analysis technology.Methods HPLC method was used to establish the relative correction factors(RCF)between protocatechuic acid and 13 other components of coumalic acid,coumarin,cinnamyl alcohol,cinnamic acid,2-methoxycinnamic acid,cinnamaldehyde,o-methoxycinnamaldehyde,vanillic,syringic acid,4-hydroxybenzoic acid,procyanidin B2,epicatechin and procyanidin C1 to be measured,and the content of each component was calculated.The QAMS method was validated using external standard method(ESM),and the comprehensive quality of Cinnamomi Cortex was evaluated using PCA,OPLS-DA and EW-TOPSIS methods.Results The methodological verification results of ESM were in accordance with the requirements;the RCF established with protocatechuic acid as the reference had good durability under different experimental conditions,and the difference in content of each component between ESM and QAMS was not significant(P>0.05);the results of multivariate statistical analysis showed that accumulative contribution rate of former 2 principle components was 90.312%.Cinnamaldehyde,2-methoxycinnamic acid,procyanidin B2 and 4-hydroxybenzoic acid had a significant impact on the quality of Cinnamomi Cortex.The results of EW-TOPSIS showed that the Pi value of 16 batches of Cinnamomi Cortex ranged from 0.147 2 to 0.768 1.The quality of Cinnamomi Cortex from different producing areas varied greatly,and the overall quality of Cinnamomi Cortex from Guangxi Province was the best,followed by that from Guangdong Province and Yunnan Province,and the quality of Cinnamomi Cortex from Fujian Province was relatively poor.Conclusion The established QAMS multi-component quantitative method combined with multivariate statistical analysis technology can be used for comprehensive quality evaluation of Cinnamomi Cortex.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective Explore the molecular mechanism by which long chain non-coding(lncRNA)MEG8 regulates the development of chronic obstructive pulmonary disease(COPD)mediated by miR-367-3p/phos-phatase and tensin homolog(PTEN).Methods Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the expression level of lncRNA MEG8 in 16HBE cells and clinical tissues of chron-ic obstructive pulmonary disease(COPD).MEG8 was overexpressed in 16HBE cells stimulated by cigarette smoke extract(CSE),and MEG8 or PTEN were simultaneously knocked down after the addition of miR-367-3p inhibitor,then MTT assay,flow cytometry,enzyme-linked immunosorbent assay,and immunoblotting were used to detect changes in cell apoptosis,proliferation,and levels of inflammatory factors.The targeting rela-tionships of MEG8,miR-367-3p,and PTEN was verified by using the dual luciferase reporting system.Results MEG8 expression was reduced in CSE stimulated 16HBE cells and COPD clinical tissue samples(P<0.05).Compared to the CSE group,overexpression of MEG8 stimulated apoptosis and inflammatory fac-tor interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αlevels decreased(P<0.05)in 16HBE cells stimulated by CSE.The expression levels of proapoptotic proteins Bax,Caspase3,and Cleared caspase3 de-creased(P<0.05),and the expression level of apoptosis inhibitory factor Bcl-2 increased(P<0.05).The double luciferase Reporter gene experiment verified that MEG8 can target to inhibit miR-367-3p(P<0.05),and miR-367-3p can target to inhibit the expression of PTEN(P<0.05),thereby inhibiting the apoptosis and inflammatory response of 16HBE cells stimulated by CSE(P<0.05).Under CSE stimulation,compared to the Control group,the addition of miR-367-3p inhibitor significantly upregulated the protein expression level of PTEN in 16HBE cells(P<0.05),enhanced cell proliferation activity(P<0.05),reduced cell apoptosis(P<0.05),significantly downregulated the expression levels of proapoptotic proteins Bax,Caspase 3,and Cleared caspase 3(P<0.05),upregulated the expression level of anti apoptotic protein Bcl-2(P<0.05),and suppressed the inflammatory factor IL-1 β,IL-6 and TNF-α Knocking down MEG8 or PTEN can restore the protein expression level of PTEN(P<0.05),inhibit cell proliferation activity(P<0.05),reverse cell apoptosis caused by miR-367-3p inhibitor(P<0.05),and regulate apoptosis related proteins(P<0.05),and enhance the in-flammatory factor IL-1 β,IL-6 and TNF-α The level of(P<0.05).Conclusion MEG8 inhibits the apoptosis and inflammatory response of 16HBE cells stimulated by CSE by regulating miR-367-3p/PTEN molecular ax-is,and may provide a potential molecular target for the treatment of COPD.

Objective:To assess the predictive accuracy and practical utility of established risk prediction models for enteral nutrition intolerance in critically ill patients. Methods:A meta-analysis was conducted to identify existing risk prediction models for enteral nutrition intolerance in critically ill patients. Eligible patients admitted to the Department of Critical Care Medicine and various ICUs of General Hospital of Eastern Theater Command from March 2023 to August 2023, meeting natriuresis criteria, were included in the study. The discrimination and calibration of the two models were assessed using the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test (H-L test). Results:Two models were analyzed, encompassing a total of 395 patients, among whom 161 experienced intolerances, resulting in an incidence rate of 40.8％. Model 1 demonstrated an AUROC of 0.838 (95％CI:0.798 ～ 0.873), while model 2 yielded an AUROC of 0.744 (95％CI:0.698 ～ 0.786). The Delong method was utilized to compare the AUROC values of the two models, revealing a statistically significant difference (P=0.0043). Notably, the model 1 exhibited superior performance compered to model 2. The H-L test for model 1 indicated fair calibration (X2=61.116, P<0.001), whereas model 2 demonstrated better calibration (X2=3.659, P=0.887). Conclusion:Model 1 exhibits superior discriminatory ability compared tomodel 2, while the calibration of model 2 surpasses that of model 1. Model 1 is well-suited for dynamic prediction, accommodating changes in patient condition over time. Conversely, Model 2 is appropriated for initial prediction following enteral nutrition initiation. Healthcare professionals can integrate bothmodels based on the specific clinical conditions to enhance predictive accutacy. Additionally, they can undertake high-quality research to develop a novel risk prediction model.

Objective:To evaluate the nutritional status and its influencing factors in esophageal cancer patients for home-based care after surgery.Methods:A total of 153 patients with esophageal cancer who underwent surgery between July 2022 and October 2023 in the General Hospital of Eastern Theater Command were enrolled in this study.The nutritional status of the patients at home in 1-month post-surgery was evaluated according to the patient-generated subjective global assessment(PG-SGA),and the possible influencing factors were analyzed.Results:Among the 153 patients,47 were well-nourished and 106 were malnourished,with an overall malnutrition rate of 69.3%.For the malnutritional patients,71 were suspected or moderately malnourished and 35 were severely malnourished.The hemoglobin levels,serum albumin levels,the route for nutrition support delivery,nutrition impact symptoms(NIS),oral nutritional supplements(ONS)and nutritional behavior were independent influencing factors of nutritional status(P<0.05),in which NIS≥2 was a risk factor for malnutrition in the patients.Normal hemoglobin and albumin levels,enteral tube feeding,oral nutritional supplement and achieving standard of nutritional behavior were protective factors for avoiding the presence of malnutrition.Conclusion:The esophageal cancer patients for home-based care after surgery have a high incidence of malnutrition.Many factors,including nutrient delivery route and nutritional behavior,were related to the occurrence of in the patients.Certain measures to the related factors should be taken early for preventing malnutrition in clinical practice.

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.