This study examined the effect of islet macrophages on β-cell function changes during type 2 diabetes mellitus (T2DM) progression based on the traditional Chinese medicine theory that " moderate fire generating qi, hyperactive fire consuming qi" . T2DM is closely associated with chronic low-grade inflammation, with islet macrophages playing a central role in this process. Under physiological conditions, islet macrophages secrete anti-inflammatory and growth factors to regulate the immune response, promote cell proliferation, and support islet β-cell survival and function, reflecting the concept of " moderate fire generating qi" . However, during the pathological process of T2DM, islet macrophages become over-activated and dysfunctional, secreting large amounts of pro-inflammatory factors that trigger severe inflammatory responses and oxidative stress. This process damages islet β-cells, disrupts the islet microenvironment and blood supply, exacerbates local inflammation and structural damage, and worsens the survival environment of β-cells. Ultimately, this leads to fewer β-cells and function loss, aligning with the " hyperactive fire consuming qi" theory, where excessive fire depletes qi and blood. This study enhances the understanding and application of traditional Chinese medicine theories in modern medicine, offering a new perspective on T2DM prevention and treatment. Regulating islet macrophage function and reducing their pro-inflammatory responses may become key strategies for preserving β-cell function and slowing T2DM progression.

BACKGROUND:As a degradable scaffold material for bone tissue engineering,lactic acid is widely used in tissue regeneration and repair research,and plays an important role in promoting tissue healing,new bone formation and angiogenesis. OBJECTIVE:To observe the effect of lactic acid degradation products on osteoclasts and to investigate the effects of lactic-interfered osteoclast conditioned medium on the proliferation,migration and tube-forming capacity of human umbilical vein endothelial cells. METHODS:(1)The mouse monocyte macrophage cell line RAW264.7 at logarithmic growth period was selected,and adherent cells were cultured in the osteoclast induction medium(DMEM medium with nuclear factor-κB receptor-activating factor ligand and 10%fetal bovine serum)containing different concentrations of lactic acid(0,5,10,20 mmol/L).After 5 days of culture,tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining were conducted.After 24 hours of culture,RT-PCR was used to detect the mRNA expression of tartrate-resistant acid phosphatase 5.(2)RAW264.7 cells at logarithmic growth period were selected and adherent cells were divided into two groups.Control group was cultured in the osteoclast induction medium,while experimental group was cultured in the osteoclast induction medium containing 10 mmol/L lactic acid.After 5 days of culture,the medium in each group was removed and the cells in the two groups were cultured in the serum-free DMEM medium for another 24 hours.Cell supernatant was then collected and used as the conditioned medium after mixed with an equal volume of DMEM medium containing 10%fetal bovine serum.Human umbilical vein endothelial cells at the logarithmic growth phase were taken and separately co-cultured with the conditioned medium of the control and experimental groups.The proliferation,migration and tube-forming ability of human umbilical vein endothelial cells were observed by cell counting kit-8 assay,migration assay,scratch assay and tube-forming assay.The mRNA and protein expression of angiogenesis-related genes and proteins were observed by RT-PCR and western blot. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining showed that 5 and 10 mmol/L lactic acid promoted osteoclastic differentiation of RAW264.7 cells and the promoting effect of 10 mmol/L lactate was more significant.RT-PCR results showed that the expression of tartrate-resistant acid phosphatase-5 mRNA of osteoclast-related genes was the highest when the lactic acid concentration was 5,10,and 20 mmol/L(P<0.05),especially 10 mmol/L.Compared with the control group,the proliferation,migration and tube-forming abilities of human umbilical vein endothelial cells were significantly increased in the experimental group(P<0.05).Compared with the control group,the expression levels of vascular endothelial growth factor and angiogenin 1 mRNA and protein were increased in the experimental group(P<0.05).To conclude,lactate-induced osteoclast conditioned medium could promote the angiogenesis of endothelial cells,and the mechanism may be related to the promotion of the expression of vascular endothelial growth factor and angiogenin 1.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

OBJECTIVE: To investigate the effects and underlying mechanisms of VX765 on osteoarthritis (OA) and chondrocytes inflammation in rats. METHODS: Chondrocytes were isolated from the knee joints of 4-week-old Sprague Dawley (SD) rats. The third-generation cells were subjected to cell counting kit 8 (CCK-8) analysis to assess the impact of various concentrations (0, 1, 5, 10, 20, 50, 100 μmol/L) of VX765 on rat chondrocyte activity. An in vitro lipopolysaccharide (LPS) induced cell inflammation model was employed, dividing cells into control group, LPS group, VX765 concentration 1 group and VX765 concentration 2 group without obvious cytotoxicity. Western blot, real-time fluorescence quantitative PCR, and ELISA were conducted to measure the expression levels of inflammatory factors-transforming growth factor β ₁ (TGF-β ₁), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Additionally, Western blot and immunofluorescence staining were employed to assess the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Thirty-two SD rats were randomly assigned to sham surgery group (group A), OA group (group B), OA+VX765 (50 mg/kg) group (group C), and OA+VX765 (100 mg/kg) group (group D), with 8 rats in each group. Group A underwent a sham operation with a medial incision, while groups B to D underwent additional transverse incisions to the medial collateral ligament and anterior cruciate ligament, with removal of the medial meniscus. One week post-surgery, groups C and D were orally administered 50 mg/kg and 100 mg/kg VX765, respectively, while groups A and B received an equivalent volume of saline. Histopathological examination using HE and safranin-fast green staining was performed, and Mankin scoring was utilized for evaluation. Immunohistochemical staining technique was employed to analyze the expressions of matrix metalloproteinase 13 (MMP-13) and collagen type Ⅱ. RESULTS: The CCK-8 assay indicated a significant decrease in cell viability at VX765 concentrations exceeding 10 μmol/L ( P<0.05), so 4 μmol/L and 8 μmol/L VX765 without obvious cytotoxicity were selected for subsequent experiments. Following LPS induction, the expressions of TGF-β ₁, IL-6, and TNF-α in cells significantly increased when compared with the control group ( P<0.05). However, intervention with 4 μmol/L and 8 μmol/L VX765 led to a significant decrease in expression compared to the LPS group ( P<0.05). Western blot and immunofluorescence staining demonstrated a significant upregulation of Nrf2 pathway-related molecules Nrf2 and HO-1 protein expressions by VX765 ( P<0.05), indicating Nrf2 pathway activation. Histopathological examination of rat knee joint tissues and immunohistochemical staining revealed that, compared to group B, treatment with VX765 in groups C and D improved joint structural damage in rat OA, alleviated inflammatory reactions, downregulated MMP-13 expression, and increased collagen type Ⅱ expression. CONCLUSION VX765 can improve rat OA and reduce chondrocyte inflammation, possibly through the activation of the Nrf2 pathway.
Rats ; Animals ; Chondrocytes/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism* ; Collagen Type II/metabolism* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; NF-E2-Related Factor 2/pharmacology* ; Inflammation/drug therapy* ; Osteoarthritis/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Dipeptides ; para-Aminobenzoates

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.

Autophagy is the main degradation and recycling pathway for abnormal aggregates and damaged organelles in cells,and it maintains the normal metabolic balance and material renewal in cells.Autophagy has neuroprotective effects and can affect the functional state of the nervous system by regulating homeostasis,development,apoptosis,and other physiological processes of neurons and glial cells.In recent years,a large number of studies have shown that nervous system diseases are closely related to abnormal autophagy,and inhibition or overactivation of autophagy affects the occurrence and development of depression,neurodegenerative diseases,and schizophrenia.Understanding the mechanisms of autophagy in nervous system diseases is of great significance for their prevention and treatment.This paper mainly reviews the current progress of autophagy research and the above diseases of the nervous system,providing a reference for further research into these diseases.

Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.

Objective To explore the expression of serum growth differentiation factor-8(GDF-8)and silent information regulator 4(Sir4)in elderly patients with chronic heart failure(CHF)and their relationship with left ventricular remodeling and cardiac function.Methods A total of 300 CHF patients admitted in our hospital from Jan 2021 to Dec 2023 were recruited and assigned into an observation group,and 100 healthy individuals who took physical examination during the same period served as control group.Based on New York Heart Association(NYHA)heart function classification,the patients in the observation group were divided into Grade Ⅰ(60 cases),Ⅱ(72 cases),Ⅲ(102 cases),and Ⅳ(66 cases)subgroups.Their clinical data were collected,serum GDF-8 and Sir4 levels were detected,left ventricular remodeling was evaluated with echocardiography,and cardiac dysfunction was assessed with NYHA cardiac function grading.Pearson and Spearman correlation analyses were used to analyze the correlation of GDF-8 and Sir4 levels with left ven-tricular remodeling and myocardial injury.Results The observation group had significantly larger left atrial diameter(LAD)and left ventricular end diastolic diameter(LVEDD),thicker left ven-tricular posterior wall thickness(LVPWT)and interventricular septum thickness(IVST),and higher left ventricular mass index(LVMI)and serum Sir4 and GDF-8 levels(42.46±4.75 mm vs 36.39±5.33 mm,54.63±7.96 mm vs 47.42±8.08 mm,9.44±1.21 mm vs 8.49±0.88 mm,9.27±1.58 mm vs 8.66±1.71 mm,141.49±5.32 g/m2 vs 106.52±7.33 g/m2,3.69±1.06 g/L vs 1.48±0.42 g/L,33.75±10.64 g/L vs 19.08±5.13 g/L,P＜0.01),but lower LVEF[(40.02±10.14)％vs(63.64±6.13)％,P＜0.01]and left ventricular remodeling index(LVRI,1.05±0.24 g/ml vs 1.32±0.33 g/ml,P＜0.01)when compared with the control group.The levels of Sir4 and GDF-8,as well as LVMI,were gradually increased,while the LVRI was decreased in Grades Ⅰ,Ⅱ,Ⅲ,and Ⅳ subgroups in turn,with statistical differences in the subgroups(P＜0.01).Pearson and Spearman correlation analyses showed that Sir4 and GDF-8 levels were positively correlated with LAD,LVEDD,LVPWT,IVST,LVMI,and NHYA cardiac function grade(P＜0.01),and nega-tively with LVEF and LVRI(P＜0.01).Conclusion Serum Sir4 and GDF-8 levels are abnormally elevated in elderly CHF patients,and their levels are positively correlated with the severity of left ventricular remodeling and the severity of cardiac dysfunction.