As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Asthma is one of the most common respiratory disease in children.Maintaining normal activity level(exercise ability) is the goal of treatment in children with asthma.However, when children with asthma do exercise, exercise-induced bronchoconstriction (EIB) may occur.EIB is a situation that needs urgent recognition and treatment, and its severity can be determined through exercise challenge testing.But exercise challenge testing needs the equipment that expensive and difficult to implement.And it has not been widely used in clinical practice.Therefore, we need to find a more convenient method to identify EIB in children with asthma and apply it to clinical practice.This article introduces the definition and pathogenesis of EIB in children with asthma, summarizes the diagnostic methods and the prevention and treatment of EIB, so as to help pediatricians understand EIB more deeply and instruct children with asthma to do exercise better.

Objective:To explore the independent influencing factors of patients with spontaneous rupture hemorrhage of primary liver cancer (PLC).Methods:A retrospective cohort study was conducted. The clinical data of 128 patients with PLC spontaneous rupture hemorrhage in Ningxia Medical University General Hospital from January 2017 to March 2022 were analyzed, including 108 males and 20 females, aged (53.4±10.6) years. According to different treatment, 128 patients were divided into liver resection group (LR, n=28), interventional group [ n=39, transcatheter arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE)], and conservative group ( n=61). Univariate and multivariate Cox regression was performed to analyze prognostic factors. The LR and TACE groups were subdivided into LR (aLR, n=15), TACE/TAE (aTACE, n=33) and LR+ TACE ( n=19) groups. Kaplan-Meier analysis was performed, and the survival rate was compared by log-rank test. Results:The median survival time of LR group and TACE group was 23 months and 21 months, respectively, with no statistical significance ( P>0.05). The median survival time (38 months) in LR+ TACE group was significantly longer than that in aLR group (10 months) and aTACE group (9 months), and the difference was statistically significant ( P<0.05). Univariate analysis showed that Barcelona Clinical Liver Cancer (BCLC)staging, tumor length ≥10.0 cm, vascular invasion, α-fetoprotein ≥400 μg/L, total bilirubin, prothrombin time and treatment affected overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Multivariate analysis showed that BCLC staging, tumor length ≥10.0 cm, Child-Pugh grade and treatment were independent influencing factors for overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Conclusion:BCLC stage, tumor length ≥10.0 cm, Child-Pugh grade and treatment method are independent predictors of overall survival in patients with spontaneous rupture of PLC. LR combined with TACE therapy can improve the survival and prognosis of patients with spontaneous rupture of primary liver cancer.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

Objective:To investigate the effects of blood pressure variability (BPV), serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels on cognitive function in patients with subcortical ischemic vascular disease (SIVD).Methods:A total of 133 patients with SIVD confirmed by craniocranial MRI admitted to Department of Neurology, Red Flag Hospital Affiliated to Mudanjiang Medical University from October 2021 to October 2022 were selected. According to Montreal Cognitive Assessment scores, they were divided into SIVD without cognitive impairment group (SIVD-NC group, n=39) and subcortical vascular cognitive impairment group (SVCI group, n=94); and 23 healthy volunteers with normal cognition who had normal brain MRI in the Physical Examination Center during the same period were chosen as control group. General data of all subjects and vascular risk factors in each group were collected, routine biochemical indexes of peripheral blood were detected, 24 h ambulatory blood pressure monitoring was performed, and serum ROS and SOD levels were detected by enzyme-linked immunosorbent assay. Statistical methods were used to analyze the risk factors for cognitive impairment, correlations of independent risk factors with cognitive function, and diagnostic value of risk factors in cognitive impairment in patients with SIVD. Results:(1) Compared with control group, SIVD-NC group had significantly increased percentages of patients with hypertension history or lacunar stroke history, and significantly increased hypersensitive C-reactive protein (hs-CRP) level ( P<0.05). Compared with control group and SIVD-NC group, patients in SVCI group had significantly older age, lower years of education, higher proportion of patients with lacunar stroke history, and increased hs-CRP level ( P<0.05). Compared with control group, SVCI group had significantly higher proportion of patients with hypertension history ( P<0.05). (2) SIVD-NC group had significantly higher ROS level than control group ( P<0.05); Compared with control group and SIVD-NC group, SVCI group had significantly increased ROS level ( P<0.05). (3) SIVD-NC group had significantly increased nighttime systolic blood pressure (nSBP) compared with control group ( P<0.05); SVCI group had significantly increased 24 h SBP, nSBP and nSBP-variable coefficient (CV) compared with control group and SIVD-NC group ( P<0.05). Compared with SIVD-NC group, SVCI group had significantly increased 24 h SBP-CV ( P<0.05). (4) The nSBP, nSBP-CV, serum hs-CRP and ROS, and lacunar stroke history were independent risk factors for cognitive impairment in SIVD patients ( OR=1.096, P<0.001, 95% CI: 1.042-1.154; OR=1.231, P=0.010, 95% CI: 1.050-1.443; OR=2.303, P=0.004, 95% CI: 1.311-4.039; OR=1.026, P<0.001, 95% CI: 1.014-1.039; OR=2.954, P=0.041, 95% CI: 1.045-8.348), and education level was a protective factor for that ( P<0.05). (5) Serum ROS and hs-CRP, nSBP, and nSBP-CV were negatively correlated with MoCA scores in SIVD patients ( r s=-0.336, P<0.001; r s=-0.503, P<0.001; r s=-0.204, P=0.018; r s=-0.309, P=0.001). (6) Serum ROS and hs-CRP, nSBP, and nSBP-CV had high diagnostic values in cognitive impairment in SIVD patients (areas under the curves: 0.874, 0.847, 0.804 and 0.702, P<0.05); combined diagnosis efficacy of multiple indexes was better (area under the curve: 0.948, P<0.05). Conclusion:Serum ROS and hs-CRP, nSBP and nSBP-CV are highly likely to be hemodynamic and serological monitoring indexes for screening of cognitive impairment in SIVD patients.

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L^-1 were divided into three administration groups with the high dose （300 mg·kg^-1）， medium dose （150 mg·kg^-1）， and low dose （75 mg·kg^-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

Objective:To investigate the safety and efficacy of transcatheter genicular artery embolization (GAE) for moderate to severe knee osteoarthritis (KOA).Methods:This prospective study included 13 patients (17 knees) with KOA who were treated with GAE from October 2020 to March 2021. The Kellgren-Lawrence (K-L) grade was 2-3 for 11 knees, and 4 for 6 knees. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) assessments were performed for all the subjects before operation. The success rate, clinical efficacy and complications were recorded after operation. Clinical outcomes were evaluated at 1 day, 1week and 1, 3, 6 months after the operation.Results:The success rate of GAE in 17 cases was 100%, and the success rate of target artery superselection was 98.4%(63/64). The baseline WOMAC pain score was 11(10, 13) and total score was 44(38, 58) for 17 knees. Post-operation follow-up WOMAC pain score were 4(3, 7), 2(1, 5), 2(1, 6) and 4(2, 6) at 1 day, 1 week, 1 month, and 3 months. Post-operation follow-up WOMAC total score were 22 (15, 34),20 (12, 24),17 (12, 26) and 20 (12, 31) at 1 day, 1 week, 1 month, and 3 months. There were 16 knees with 6 month follow-up assessment, with the WOMAC pain score of 2.5(2, 5), and the total score of 15(12, 26). Significant difference was found in the WOMAC pain score between baseline and the 1 day, 1 week, 1, 3 and 6 months follow up ( Z=-3.631, -3.623, -3.622, -3.622, -3.532, all P<0.001); also, the total score was statistically significant different between the baseline and the 1 day, 1 week, 1, 3 and 6 months follow up ( Z=-3.639, -3.634, -3.646, -3.527, -3.532, all P<0.001). At 3 months follow-up, there was 1 knee recognized clinical failure. Post-operative adverse reaction in this group included skin ecchymosis in femoral artery puncture area ( n=3), knee joint stiffness and pain within 1 week ( n=4),and clanging joints during postoperative activities ( n=6). Conclusion:GAE is a feasible and safe procedure with obvious short-term curative effect, which can alleviate pain symptoms and improve restricted movement in patients with KOA.