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*

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 compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma. METHODS: A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively. RESULTS: Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05). CONCLUSION Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.
Humans ; Robotics ; Osteoma, Osteoid/surgery* ; Orthopedics ; Blood Loss, Surgical ; Retrospective Studies ; Neoplasm Recurrence, Local ; Minimally Invasive Surgical Procedures ; Bone Neoplasms/surgery* ; Analgesics ; Treatment Outcome

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.

Objective To investigate the correlation between red blood cell distribution width(RDW),systemic immune-inflammation index(SII)and major depressive disorder(MDD).Methods The clinical data of 176 MDD patients hospitalized in the clinical psychology department of our hospital from 2020 to 2022 and 209 non-MDD comparators who were routinely examined in Hebei General Hospital were retrospectively analyzed.Blood analysis was conducted to obtain values of RDW,SII,and red blood cell distribution width/platelet ratio(RPR).The data was used to plot the receiver operator characteristic(ROC)curve to determine the optimal threshold and the area under the curve(AUC)for RDW to discriminate between patients and controls.Result Patients in the MDD group had significantly higher RDW[median and quartiles:13.20(12.70,13.98)vs.12.80(12.40,13.35)],and SII levels[median and quartiles 510.87(350.95,878.12)vs.405.33(313.74,539.92)]compared with those in non-MDD group(P<0.05).There was no significant difference in RPR between the two groups(P>0.05).Multifactorial logistic regression analysis showed that RDW was positively correlated with MDD after adjusting for confounders(OR=3.086,95% CI:1.926-4.944).ROC curve showed that the optimal threshold for RDW to differentiate the risk of developing MDD was 12.85,with an AUC of 0.647(95% CI:0.592-0.702;P<0.001).Conclusion Present study shows that high RDW is a risk factor for the occurrence of MDD and an important parameter for the risk of developing depression.

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.