With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

AIM:This study explores how the combination of rapamycin(Rapa)and flagellin(FliC)affects the inhibition of 4T1 breast cancer cells.The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro.METHODS:4T1 breast cancer cells were divided into four groups:control group,Rapa group,FliC group,and Rapa+FliC group.The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry.Concurrently,the KEGG pathway of differentially expressed genes(DEGs)was analyzed by high-throughput mRNA sequencing.Furthermore,the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING.The PPI network of DEGs was then constructed,and the Hub genes were sub-sequently screened.The protein expression of the Hub gene was verified based on the HPA database.RESULTS:CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibi-tion and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone(P<0.05).Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group,predominantly in the PI3K/Akt signaling pathway.In contrast,DEGs between the FliC group and control were mainly concentrated in signaling path-ways like NOD-like receptor signaling.Additionally,150 DEGs were identified between the Rapa+FliC group and the Ra-pa group,focusing primarily on pathways such as mTOR.From the protein-protein interaction(PPI)network,ten hub genes,including Atm and Itga2,were identified.CONCLUSION:The combination of Rapa+FliC could inhibit the via-bility of 4T1 breast cancer cells in vitro and promote apoptosis,potentially through the PI3K/Akt/mTOR signaling path-way.The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy.

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

Objective To investigate the effects of neuronal pentraxin 2(Nptx2)on complement system,microglia activation and synaptic density in mice with Alzheimer's disease(AD).Methods Six-months-old APPswe/PS1dE9 double transgenic mice were divided into model group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and model+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 × 1010 GC),6-months-old wild-type mice were divided into control group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and control+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 x 1010 GC),with 12 mice in each group.One month later,the cognitive function of mice in each group was evaluated by Morris Water Maze test.The expression levels of Nptx2 and Iba1 proteins were measured by Western blot,the contents of complement related proteins were measured by enzyme linked immunosorbent assay,and the synaptic plasticity was evaluated by Golgi staining.Results The resident time in the platform quadrant of control,control+AAV-Nptx2,model and model+AAV-Nptx2 groups were(44.72±10.92),(53.32±10.29),(21.92±3.80)and(36.47±6.41)s;the number of crossing the platform were 10.08±2.64,9.58±3.09,2.25±1.29 and 5.92±1.38;the relative expression levels of Nptx2 protein were 0.33±0.06,0.63±0.10,0.09±0.03 and 0.57±0.22;the relative expression levels of Iba1 protein were 0.17±0.06,0.23±0.08,0.97±0.16 and 0.40±0.14;the synaptic densities were 22.75±4.27,29.25±4.78,8.25±2.99 and 23.75±4.86.Compared with the model group,the differences of above indexes in the model+AAV-Nptx2 and control groups were statistically significant(all P＜0.05).Conclusion Overexpression of Nptx2 protein can inhibit the activation of complement system,reduce the activation of microglia,and increase the synaptic density to alleviate cognitive impairment in AD mice.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective To observe the value of apparent diffusion coefficient(ADC)for quantitatively evaluating progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.Methods Twenty healthy adult rabbits were selected to establish limb high-voltage electrical burn models,which were randomly divided into 0.5,24,48 and 72 h groups(each n=5).MR diffusion weighted imaging(DWI)was collected for each group at 0.5,24,48 and 72 h after modeling,and the injured core muscles of the right hind limb and the normal muscles of the contralateral limb were taken for HE staining.The muscle's ADC,muscle fiber density(MFD)and muscle fiber diameter(D)values at the injured core of current entry and exit were compared,and those of normal muscle were also analyzed.The correlations of ADC values in injured core muscle and MFD or D values were investigated.Results There were significant differences of ADC values of injured core muscle at both the entry and exit and normal muscle,also of ADC values of injured core muscle at the entry and exit within each group(all P＜0.05).ADC values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),but ADC values of normal muscle were not significantly different among different time points(P＞0.05).MFD values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),while MFD values of the normal muscle,D values of the injured core muscle at the entry and exit and normal muscle were not significantly different among time points(all P＞0.05).ADC value of the injured core muscle was positively correlated with MFD value and negatively correlated with D value(rs=0.846,r=-0.507,both P＜0.05).Conclusion ADC could quantitatively evaluate the progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.