ObjectiveTo observe the effect of water extract of Mori Folium （MLE） on oxidative stress in adipose tissue of type 2 diabetes mellitus （T2DM） mice and explore its mechanism. MethodTwenty-four male db/db mice were randomly divided into model group， metformin group， low-dose MLE （MLE-L） group， and high-dose MLE （MLE-H） group according to their body weight and blood glucose， with six mice in each group， and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg^-1 metformin suspension， and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg^-1 and 4 g·kg^-1 MLE， while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight， subcutaneous fat index， fasting blood glucose （FBG）， and oral glucose tolerance level （OGTT） of the mice were detected， and serum superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured. The expression levels of silent information regulator 1 （SIRT1） and NADPH oxidase type 4 （NOX4） protein in subcutaneous adipose tissue of the mice were detected by Western blot. ResultThe FBG level， OGTT， and subcutaneous fat index of T2DM mice were significantly decreased （P<0.05， P<0.01） after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased， while the level of oxidative stress damage marker MDA was significantly decreased （P<0.05， P<0.01）. The expression of SIRT1 protein in adipose tissue was significantly increased， while the expression of NOX4 protein was significantly decreased （P<0.05， P<0.01）. ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.

ObjectiveTo investigate the protective effects of Mori Folium extract （MLE） on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb （db/db） mice were randomly divided into model group， metformin group， low-dose group of MLE （MLE-L）， and high-dose group of MLE （MLE-H） according to their fasting blood glucose （FBG）， with six mice in each group， and other six C57BLKS/JGpt wild littermate （m/m） mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage， and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight， bilateral kidney weight， and FBG were measured， and an oral glucose tolerance test （OGTT） was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin （HE） and periodic acid-silver （PAS） staining， and serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in serum and urinary microalbumin （U-mAlb） of mice. The expression levels of toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor-kappa B p65 （NF-κB p65） protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group， the body weight， absolute renal weight， FBG， and the area under the curve （AUC） of OGTT of mice in the model group were significantly increased （P<0.01）， and the levels of SCr， BUN， and U-mAlb， as well as TNF-α and IL-6 in serum were significantly increased （P<0.01）. The glomerular basement membrane in the kidney tissue of mice was thicker， with obvious inflammatory cell infiltration. The protein expression levels of TLR4， MyD88， and NF-κB p65 in the kidney tissue of mice were increased significantly （P<0.01）. Compared with the model group， there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced （P<0.05， P<0.01）. The FBG levels of mice in the metformin， MLE-L， and MLE-H groups started to decrease after treatment for four to eight weeks （P<0.05， P<0.01）. The AUC of mice in the MLE-H and metformin groups was significantly decreased （P<0.01）. The levels of SCr， BUN， and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）， and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased （P<0.01）. The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）. The renal tissue pathology of mice in each drug administration group was improved to varying degrees， and the protein expression levels of TLR4， MyD88， and NF-κB p65 in the MLE-H group were decreased significantly （P<0.05， P<0.01）. ConclusionMLE can improve the renal structure and function of db/db diabetic mice， and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Mori Folium， the dried leaves of Morus alba， is widely used in clinical practice for dispersing wind and heat， clearing the lung and moistening dryness， soothing the liver and improving vision， and cooling blood and stopping bleeding. It has been used to regulate blood glucose since ancient times， and modern studies have shown that the active components of Mori Folium for lowering blood glucose mainly include flavonoids， alkaloids， polysaccharides， and phenols. These components are mainly extracted by solvents such as water and alcohols with the assistance of ultrasound and microwave. In addition， new extraction methods are emerging， such as CO₂ supercritical fluid extraction， enzymatic hydrolysis， and cloud point extraction. Mori Folium lowers blood glucose via multiple components， pathways， and targets. Specifically， it can improve glucose and lipid metabolism， protect pancreatic β cells， and alleviate insulin resistance to reduce the damage caused by hyperglycemia and restore normal physiological functions. Although a large number of studies have been carried out on diabetes， the causes and radical treatment methods remain to be explored， and diabetes is still a major disease that endangers human health and needs to be solved urgently. The articles about extraction process and mechanism of active components in Mori Folium for lowering blood glucose were retrieved from the China National Knowledge Infrastructure （CNKI）， Web of Science， and PubMed. We analyzed the applicable extraction methods for the blood glucose-lowering components such as flavonoids， polysaccharides， and alkaloids in Mori Folium， and compared the conventional and emerging methods. Furthermore， we summarized our research achievements in the extraction of active components from Mori Folium and the blood glucose-lowering effect and mechanisms. This review aims to provide theoretical support for the optimization of the extraction process， the research on the blood glucose-lowering components and mechanism， and the development of new drugs and clinical application of Mori Folium.

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.

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 explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

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.

Objective:To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds.Methods:A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association.Results:The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases.Conclusions:The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

Objective:To explore the effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with severe wrist electric burn.Methods:A retrospective observational study was conducted. From January 2017 to December 2020, 4 patients with wrist high-voltage electric burn admitted to the Department of Burns of the First People's Hospital of Zhengzhou and 4 patients with wrist high-voltage electric burn admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital met the inclusion criteria, including 6 males and 2 females, aged 12 to 52 years. They were all classified as type Ⅱ wrist high-voltage electric burns with median nerve defect. In the first stage, the wounds were repaired with free anterolateral thigh femoral myocutaneous flap. In the second stage, the free gracilis muscle flap combined with sural nerve transplantation was used to reconstruct the digital flexion and sensory function of the affected hand in 3 to 6 months after wound healing. The cut lengths of muscle flap and nerve were 32 to 38 and 28 to 36 cm, respectively. The muscle flap donor area and nerve donor area were both closed and sutured. The survival condition of gracilis muscle flap and sural nerve, the wound healing time of recipient area on forearm, the healing time of suture in muscle flap donor area and nerve donor area were observed and recorded after operation, and the recovery of donor and recipient areas was followed up. In 2 years after operation, the muscle strength of thumb and digital flexion and finger sensory function after the hand function reconstruction were evaluated with the evaluation criteria of the hand tendon and nerve repair in the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association.Results:All the gracilis muscle flap and sural nerve survived successfully after operation. The wound healing time of recipient area on forearm was 10 to 14 days after operation, and the healing time of suture in muscle flap donor area and nerve donor area was 12 to 15 days after operation. The donor and recipient areas recovered well. In the follow-up of 2 years after operation, the muscle strength of thumb and digital flexion was evaluated as follows: 4 cases of grade 5, 3 cases of grade 4, and 1 case of grade 2; the finger sensory function was evaluated as follows: 4 cases of grade S3 +, 2 cases of grade S3, and 2 cases of grade S2. Conclusions:For patients with hand dysfunction caused by severe wrist electric burn, free gracilis muscle flap combined with sural nerve transplantation can be used to reconstruct the digital flexion and sensory function of the affected hand. It is a good repair method, which does not cause great damage to thigh muscle flap donor area or calf nerve donor area.

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.