Diabetic nephropathy （DN） is a serious chronic microvascular complication of diabetes mellitus （DM） and a major cause of end-stage renal disease （ESRD）. It is characterized by gradual and progressive decline of renal function， which eventually leads to glomerular sclerosis， interstitial fibrosis and other serious lesions. Although modern medical treatment can partially relieve the symptoms， there are limitations such as single therapeutic effect， low long-term therapeutic effect， and severe side effects. Traditional Chinese medicine （TCM）， with a wide effect range， lasting efficacy， and high safety， often exerts unique therapeutic effect in the clinical treatment of DN. Nuclear factor E₂-related factor 2 （Nrf2）， an anti-oxidative stress transcription factor， has received much attention. It can regulate multiple upstream and downstream factors such as heme oxygenase-1 （HO-1）， NAD（P）H： quinone oxidoreductase 1 （NQO1）， nuclear factor-κB （NF-κB）， NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， glutathione peroxidase 4（GPX4）， and p62， playing a role in cell protection by intervening in different mechanisms. A large number of studies have found that TCM active ingredients and compound prescriptions can inhibit oxidative stress， inflammation， pyroptosis， apoptosis， and ferroptosis or promote autophagy by regulating the signaling pathway composed of Nrf2 and the above-mentioned related factors， thus protecting the kidney function， reducing proteinuria， alleviating kidney fibrosis， and significantly ameliorating DN. This review briefly summarized the structure and function of Nrf2， clarified the regulation mechanism of Nrf2 in DN， focused on the main studies on the intervention of DN by the effective components and compound formulas of TCM through the targeted activation of the Nrf2 signaling pathway in the past five years， and discussed the huge potential of Nrf2 signaling pathway as a target for the treatment of DN. The aim is to provide reference for the development and promotion of new drugs in clinical practice and promote the innovation and development of the treatment methods for DN in the future.

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by absolute or relative insufficiency of insulin secretion. As the disease progresses， patients begin to suffer from diabetic nephropathy， diabetic cardiomyopathy， non-alcoholic fatty liver disease or other complications， which increase the burden on the patients. Moreover， the number of patients is increasing， which brings a heavy burden to the society. Ferroptosis is a new type of programmed cell death which has attracted wide attention in recent years. It refers to the cell death caused by the excessive accumulation of lipid peroxide under the overload of iron ions. Studies have discovered that ferroptosis exists in diabetes mellitus and its complications. Inhibiting ferroptosis can greatly slow down the occurrence and progression of diabetes mellitus and its complications. Chinese medicine， the unique medical treasure in China， acts in a multi-pathway， multi-target manner and is praised for the cheap price， low toxicity， and mild side effects. It has been widely used in the treatment of diabetes mellitus and its complications and has demonstrated definite therapeutic effects， bringing the good news for the majority of patients. The regulation of ferroptosis by Chinese medicine may be a new direction for the treatment of diabetes mellitus and its complications in the future. This paper briefly describes the mechanism of ferroptosis， explores the relationship of ferroptosis with diabetes mellitus and its complications， summarizes the research status of Chinese medicine interventions， and puts forward suggestions， aiming to provide a reference for further research on the treatment of diabetes mellitus and its complications with Chinese medicine.

Nonalcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）. Cell death caused by iron-lipid disorder is a new mode of regulating programmed cell death， which is characterized by lipid peroxidation induced by the accumulation of lipid reactive oxygen species and excessive accumulation of iron ions induced by iron metabolism disorders. Among them， iron homeostasis disorder and metabolic pathway disorder are the main causes of iron-lipid disorder， which play an important role in a variety of pathological processes related to cell death. Because the liver is an important organ for iron storage and lipid metabolism， iron-lipid disorder is an ideal target for liver disease， and inhibition of iron-lipid disorder may become a new strategy for the treatment of NAFLD. However， the pathogenic relationship and mechanism between NAFLD and iron-lipid disorder have not been fully elucidated. Based on the complex molecular regulation mechanism of iron-lipid disorder， by expounding the role of iron-lipid disorder in NAFLD and its related mechanism， this paper summarizes the research status of traditional Chinese medicine on the target treatment of NAFLD in recent years， so as to provide a new perspective and point out a new direction for the treatment of NAFLD in the future.

ObjectiveTo observe the effect of bilateral sequential repetitive transcranial magnetic stimulation on the motor function of upper limbs in stroke patients. MethodsFrom December, 2020 to December, 2022, 62 stroke inpatients in the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were included. They were randomly divided into control group (n = 31) and observation group (n = 31). Both groups accepted conventional medicine and rehabilitation, as well as electroacupuncture antagonistic muscle therapy. Before electroacupuncture, the observation group acceped low-frequency repetitive transcranial magnetic stimulation at primary motor cortex (M1) on the healthy side, followed by intermittent theta burst stimulation at M1 on the affected side, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index (MBI) and modified Ashworth Scale (MAS), and motor evoked potential (MEP) latency was compared before and after treatment. ResultsOne patient dropped down in the observation group, and no adverse event happened. After treatment, the scores of FMA-UE and MBI significantly increased (|t| > 9.953, P < 0.001), and the score of MAS and the latency of MEP significantly decreased (|t| > 5.043, P < 0.001) in both groups; while all of them were better in the observation group than in the control group (|t| > 2.237, P < 0.05). ConclusionBilateral sequential repetitive transcranial magnetic stimulation can effectively promote the recovery of upper limb motor function in stroke patients.

ObjectiveTo observe the effect of Hedysari Radix polysaccharide （HRP） on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription protein 3 （STAT3） signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group， irbesartan group （irbesartan suspension， 22.75 mg·kg^-1）， and high-， medium-， and low-dose HRP groups （HRP suspension， 200， 100， 50 mg·kg^-1） according to the body weight， with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage， while those in the normal group and the model group received distilled water at 5 mL·kg^-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid （UA）， triglycerides （TG）， and total cholesterol （TC） were detected. Periodic acid-Schiff （PAS） staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and mRNA expression levels of JAK2， STAT3， suppressor of cytokine signaling 3 （SOCS3）， and tumor necrosis factor-α （TNF-α） in the kidney. ResultAfter 12 weeks of treatment， compared with the normal group， the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA， TG， and TC levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA， TG， and TC levels （P<0.05， P<0.01）. Compared with the normal group， the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.05， P<0.01）. ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent， and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.

Diabetic nephropathy （DN）， as one of the common chronic microvascular complications of diabetes， has become the main cause of renal failure in end-stage renal disease in China， increasing the risks of renal dialysis and kidney transplantation in diabetes patients. It is the leading cause of death in people with diabetes. The latest research on DN has focused on the gene level. microRNAs （miRNAs） are a family of endogenous accessible short-chain non-coding RNA molecules. By acting on a particular target， they activate or inhibit its mediated signaling pathways and related molecules， playing an important role in the occurrence and development of DN. They have become microeconomic factors for the prevention and treatment of DN. Traditional Chinese medicine （TCM） has a long history in the diagnosis and treatment of DN and has unique advantages such as significant curative effect and few side effects. A large number of studies have proved that TCM can target miRNA to affect multiple signaling pathways， participate in the regulation of inflammatory response， pyroptosis， mesenchymal transdifferentiation， and other pathological changes， and delay the further development of DN. Therefore， this study discusses the biogenesis mechanism of miRNA and its action mechanism in disease-related signaling pathways based on TCM diagnosis and treatment approaches from the perspective of miRNA， and summarizes the effect of TCM targeting miRNA on the disease-related signaling pathways and on DN. Thus， this study is expected to provide a theoretical reference for exploring the progress of TCM intervention in DN from the perspective of genes.

ObjectiveTo observe the effect of Hedysarum polysaccharides （HPS） on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group， irbesartan group， and high， middle， and low-dose HPS experimental groups according to their body mass， with 10 mice in each group， and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg^-1·d^-1 distilled water， the irbesartan group was given 22.75 mg·kg^-1·d^-1 irbesartan suspension， and the high， middle， and low-dose HPS experimental groups were given 200， 100， and 50 mg·kg^-1·d^-1 HPS suspensions， respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state， blood glucose （GLU）， 24 h urine protein （UTP）， blood creatinine （SCr）， and urea nitrogen （BUN） of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining （HE）. The protein and mRNA expression levels of Wnt1， β-catenin， glycogen synthesis kinase-3β （GSK-3β）， and phosphorylated GSK-3β （p-GSK-3β） in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultAfter treatment for 12 weeks， as compared with the normal group， the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU， 24 h UTP， SCr， and BUN in the model group increased （P<0.01）. As compared with the model group， the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent， and the levels of SCr， BUN， and 24 h UTP in the high and middle-dose HPS groups decreased （P<0.05，P<0.01）. As compared with the normal group， the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the model group were higher （P<0.01）， while the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group （P<0.05，P<0.01）. ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent， and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.

ObjectiveTo explore the current status, hot spots and development of researches on post-stroke dysphagia in recent five years with visualization analysis. MethodsResearches on post-stroke dysphagia were retrieved from Web of Science Core Collection, from January 1st, 2017 to December 31st, 2021, and reviewed with CiteSpace 5.7.R5 software. ResultsA total of 857 articles were included. The annual number of articles increased with time, published from 61 countries/regions, by 211 institutions and 247 authors. The United States, Japan and China were the most prolific countries, and the University of Manchester was the leading institution. The top three authors were Dziewas R, Wakabayashi H and Hamdy S. The keywords bursting in recent three years included prediction, severity, percutaneous endoscopic gastrostomy, accuracy and early management; co-word clustering showed that researches might be mainly about neuromuscular electrical stimulation, swallowing screening, stroke-associated pneumonia, evidence-based practice, etc. ConclusionThe researches in the field of post-stroke dysphagia have been increasing.

Objective To investigate the imaging characteristics of nontraumatic spontaneous intramural hematoma of small bowel secondary to warfarin therapy.Methods The retrospective and descriptive study was conducted.The clinical data of 12 patients with nontraumatic spontaneous intramural hematoma of small bowel secondary to warfarin therapy who were admitted to the First People's Hospital of Wenling (11 patients) and Taizhou Hospital of Zhejiang Province (1 patient) between January 2010 and December 2016 were collected.Patients received plain and enhanced scans of computed tomography (CT).Patients stopped warfarin therapy,received intramuscular injection of vitamin K1 and fresh-frozen plasma transfusion.Observation indicators:(1) primary signs of CT:① small bowel wall thickening;② increased density of small bowel wall;(2) secondary signs of CT:intestine lumen stenosis,intestinal pneumatosis,perienteric changes and other concomitant signs;(3) treatment situations.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).Results Twelve patients received total abdomen plain scans of CT,and 7 received total abdomen enhanced scans of CT.(1) Primary signs of CT:① Small bowel wall thickening.CT of 12 patients showed solitary,homogeneously symmetric,consecutive and diffuse thickening of small bowel wall,including ileal involvement in 7 patients and jejunum involvement in 5 patients.Ascending part of duodenum of 3 patients involved the 2nd and 3rd groups small bowel.The average length of involved small bowel was 30.7 cm (range,11.0-58.0 cm).There was no multifocal thickening or colonic involvement.Of 12 patients,10 and 2 showed moderate thickening (thickness was 1.0-2.0 cm) and severe thickening (thickness ＞ 2.0 cm),and the thickest small bowel wall was 2.5 cm.② Increased density of small bowel wall.Twelve patients showed varying degrees of increased density of small bowel wall,with an average value of 49.7 HU (range,36.0-63.4 HU).Of 12 patients,homogeneously increased whole layer density of small bowel wall were detected in 4 patients,higher submucous layer density of small bowel compared with serosal layer density in 4 patients,and all of the above characteristics in 4 patients.Enhanced scans of CT in 7 patients showed enhancement in small bowel mucosal layer and serosal layer,no obvious enhancement in the submucous layer of small bowel wall,clear layers,and a target sign when small bowel lumen was perpendicular to scan slice,including 5 patients with obvious enhancement in small bowel mucosal layer,spring-like change,and clear imaging in portal vein phase.(2) Secondary signs of CT:① Intestine lumen stenosis:12 patients had varying degrees of intestine lumen stenosis.Five patients were complicated with small bowel obstruction,showing a gas-liquid level.② Intestinal pneumatosis:2 of 12 patients showed patchy and mottled gas shadow.③ Perienteric changes and other concomitant signs:12 patients showed obviously increased fat density in surrounding area of involved small bowel and corresponding mesenteric area,and indistinct outside small bowel,including 8 with lots of lath-like high density shadow in surrounding area of small bowel and mesenteric area.The varying degrees of hemoperitoneum were seen in 12 patients.(3) Treatment situations:of 12 patients,9 underwent correct treatments,8 of them were improved,and 1 of them with persistently severe abdominal pain underwent urgent explorative laparotomy,showing hemorrhage and necrosis,and then underwent surgery;3 didn't undergo correct treatment,without improved or severe symptoms.Conclusion Patients undergoing anticoagulant therapy show acute abdominal pain with abnormal coagulation function,small bowel wall thickening and increased density by CT scans,hemoperitoneum complicated with intestine lumen stenosis,small bowel obstruction and hematocele in surrounding area of small bowel and mesenteric area,these are highly indicative of nontraumatic spontaneous intramural hematoma of small bowel secondary to warfarin therapy.