BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

BACKGROUND:Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases.Moreover,compounds targeting efferocytosis have shown good therapeutic effects. OBJECTIVE:By reviewing the effects of obesity on macrophage efferocytosis,to analyze the key mechanism by which obesity inhibits efferocytosis,to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases,so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases,aiming to provide new strategies for disease prevention and treatment. METHODS:The English search terms were"efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment,"which were used for literature retrieval in PubMed and Web of Science.The Chinese search term was"efferocytosis,"which was used for literature retrieval in CNKI,VIP and WanFang datebases.Ninety-nine papers were finally included in the review analysis after a rigorous screening process. RESULTS AND CONCLUSION:In the process of efferocytosis,the"Find me"and"Eat me"processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells.The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages,which are crucial for efferocytosis activity.These results suggest that the"Find me"and"Eat me"factors mainly reflect the condition of apoptosis,and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages.Obesity inhibits efferocytosis,and shows an inhibitory effect on most digestive factors,but has a stress-induced activation effect on most"Find me,""Eat me"and cytoskeletal recombination factors,which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of"Find me"and"Eat me"factors.Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis.The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases,but the efferocytosis inhibitors in tumor tissue show good anticancer effects,suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation.Efferocytosis is a relatively new concept proposed in 2003,with a short research history and complex efferocytosis factors.Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.

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.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.