[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

Objective To analyze the correlation between hemoglobin(Hb),anemia,and sarcopenia in the elderly population in Chongqing communities.Methods A cross-sectional study was conducted on elderly individuals who underwent healthy examinations at 5 community health service centers in Chongqing from March to August 2023.Demographic characteristics,social factors,body composition measurement,grip strength,6-meter gait speed and blood tests were assessed.Receiver operating characteristic(ROC)curve was utilized to evaluate the accuracy of Hb in predicting sarcopenia,and the Youden index was employed to determine the optimal Hb cut-off value for diagnosing sarcopenia and its components.Both unadjusted and adjusted logistic regression analyses were performed to examine the relationship between Hb and anemia with sarcopenia and its components.Results A total of 531 elderly populations were included,with an average age of(71.1±6.5)years.The overall prevalence of sarcopenia was 13.6%(72/531),including 29 males(40.3%)and 43 females(59.7%).Unadjusted analyses showed that Hb was correlated with sarcopenia,decreased muscle mass,slower gait speed,and reduced grip strength(P<0.05).After adjusting for all potential risk factors,Hb was still significantly associated with sarcopenia and reduced grip strength(P<0.05).For every 10 g/L increase in Hb,the risk of sarcopenia decreased by 2.3%,and the risk of reduced grip strength decreased by 1.7%(P<0.05).Anemia was correlated with sarcopenia,reduced muscle mass,and decreased grip strength in unadjusted analyses(P<0.05),while the correlation between anemia and reduced grip strength remained significant after adjustment for all potential risk factors(P<0.05).The optimal Hb cut-off value for diagnosing sarcopenia in males and females were 148 g/L and 128 g/L,respectively.Conclusions Hb is an independent risk factor for sarcopenia and reduced grip strength.Anemia is associated with sarcopenia,but is not an independent risk factor for sarcopenia.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective To observe the effect of esketamine on postoperative recovery in children after endoscopic adenoidectomy.Methods Sixty pediatric patients who underwent adenoidectomy with endoscope from Jan 2022 to Jan 2023 in Eye&ENT Hospital,Fudan University were enrolled.The pediatric patients were randomly divided into hydro-morphine group(n=30)and esketamine group(n=30).Anesthesia induction:lidocaine 1.5 mg/kg,propofol 2.5 mg/kg and remifentanil 4 μg/kg were injected intravenously,and then the endotracheal tube was used for airway management.Anesthesia maintenance:remifentanil infusion was at 0.2-0.5 μg·kg-1·min-1 and the end tidal concentration of sevoflurane was at 0.7-1.0 minimum alveolar concentration(MAC).At the end of surgery,either hydromorphone 0.01 mg/kg or esketamine 0.5 mg/kg were administered for postoperative pain control.Time to resume spontaneous breathing was recorded.Other parameters included respiratory rate per minute,duration of stay in the post-anesthesia care unit,hemodynamic profiles.The adverse events including agitation and desaturation were also of note.Results Children in esketamine group resumed spontaneous breathing faster(P=0.048),had faster respiratory rate when recovery of spontaneous breathing(P=0.001)and lower concentration of end tidal CO2(P=0.005).The findings suggested that esketamine did not impair respiratory function.Compared to hydro-morphine group,children in esketamine group had shorter stay in the post-anesthesia care unit with statistical difference(P=0.020).Esketamine had no effect on heart rate and blood pressure,so there were less adverse events.Conclusion Compared with 0.01 mg/kg hydro-morphine,0.5 mg/kg esketamine does not impair respiratory function and it facilitate fast recovery in children undergoing endoscopic adenoidectomy after general anesthesia.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.