Objective:To examine the effects of Zishenwan Prescription on bile acid metabolism in mice with diabetic encephalopathy; To explore its mechanism of improvement of diabetic encephalopathy.Methods:Male C57BL/6J mice were used to replicate the mouse model of type 2 diabetes mellitus by using high-fat chow and a single intraperitoneal injection of streptozotocin (120 mg/kg). The mice were screened for diabetic encephalopathy by using the Morris water maze test after 8 weeks of continuous stimulation with hyperglycemia, and were divided into model group and Zishenwan Prescription group according to random number table method, with 12 mice in each group. The mice in the Zishenwan Prescription group were treated with the crude extract of Zishenwan Prescription (9.36 g/kg) by gavage, and the normal group and the model group were treated with the same volume of distilled water once a day for 8 weeks. At the end of the treatment, Morris water maze test was used to investigate the cognitive function of diabetic encephalopathy mice; cresyl violet staining was used to detect the number of granule neurons in the hippocampus; serum and feces were collected to detect the content of bile acids by liquid-liquid coupling; hepatic bile acid synthase CYP7a1 and CYP27a1, farnesol X receptor (FXR), fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), and ileocecal apical sodium-dependent bile acid transporter protein (ABST) mRNA levels were detected by using fluorescence quantitative PCR assay.Results:Compared with the model group, mice in the Zishenwan Prescription group had shorter evasion latency time ( P<0.05 or P<0.01), decreased time to first reach the platform ( P<0.01), increased number of times to traverse the platform ( P<0.01), and reduced neuronal cell damage in hippocampal area; mice in the Zishenwan Prescription group showed decreased serum and fecal total bile acid content ( P<0.05 or P<0.01); the liver CYP7a1 and CYP27a1 mRNA expressions increased ( P<0.01), and FXR and FGF15 mRNA expressions decreased ( P<0.01); ileal ABST mRNA expression decreased ( P<0.01). Conclusion:Zishenwan Prescription may regulate bile acid metabolism, inhibit FRX-FGF15/FGFR4 signaling and ABST expression to promote new bile acid synthesis and conjugated bile acid reabsorption, and thus improve cognitive function in diabetic encephalopathy mice.

Objective:To explore the clinical effect of perforator pedicled propeller flap (PPPF) in reconstruction of soft tissue defect in ankle and foot, as well as the role of preoperative ultrasonography in assistance of the location of perforators in donor site.Methods:From January 2017 to June 2023, the Department of Microorthopedics of the Second Affiliated Hospital of Luohe Medical College of Higher Education applied PPPF to reconstruct small and medium-sized soft tissue defects in the ankle and foot for 26 patients. The patients were 17 males, 9 females, aged 18 to 68 years old with 46 years old in average. The defect sites were 3 in forefoot and 6 in midfoot and combined with different degrees of tendon and bone exposure, 17 in ankle and heel and combined with various degrees of bone exposure, 12 with ankle open injury and 5 with Achilles tendon exposure. The area of soft tissue defects ranged from 2.5 cm×1.5 cm to 16.0 cm × 6.5 cm. The width of injury was measured before surgery, and a HHD was used to detect the perforators proximal to the defect site, and then high-frequency CDU was used to locate and confirm the location of the perforator and its alignment, blood flow and diameter. The line drawn between the 2 perforators was set as the axis of flap. The donor site was assessed by a "pinching and lifting" method to determine a direct closure of donor site or to have it closed by a flap transfer. The sizes of flap were from 2.8 cm×1.5 cm to 24.0 cm×7.5 cm. Twenty-two donor sites were directly closed and 4 received flap transfers. Four flaps had sutures with the skin nerves in the recipient site. Masquelet technique was performed in 6 patients with bone defects in the surgery. Patients received outpatient reviews with 1-2 weeks of intervals in the first 2 months after surgery, and X-ray reviews per 1-2 months for those with bone implants until bone healing.Results:All flaps survived successfully without any special treatment after surgery, except 1 flap that had blood vessel congestion and showed swelling and poor blood supply to the distal flap at 24 hours after surgery. The blood vessel congestion was revised by removal of part of the suture at the tip of flap pedicle. One week later, the tip of the flap remained with a small area of necrosis, which was then healed after dressing changes. A total of 21 patients were included in postoperative follow-up with 4 months to 3 years. All of the flaps had satisfactory appearance, colour and texture, and without any ulceration. Three cases of nerve suture were also included in follow-up. According to the assessment criteria of British Medical Research Council (BMRC), the sensory recovery of the flaps was found of S 2 in 1 flap and S 3 in 2 flaps. According to the American Orthopaedic Foot and Ankle Society (AOFAS), the ankle-hindfoot function scores, there were excellent in 16 patient and good in 5 patients. Conclusion:With the assistance of ultrasound, the PPPF can be effectively used in reconstruction of soft tissue defects in ankle and foot.

Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.

Modern medicine has made remarkable achievements in safeguarding people's life and health, however, it is increasingly found that in the face of complex diseases, selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect, and is prone to induce drug resistance, toxic side effects. Traditional Chinese medicine (TCM) has a long history of clinical application, and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases, digestive diseases, skin diseases, rheumatism and immunity diseases, and adjuvant treatment of tumors has been proven to have obvious advantages. However, its modern research is relatively lagging behind, and in the face of the aging society and the characteristics of the modern disease spectrum, the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs. Focusing on the key issues of TCM development in the new era, the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development, and dominant diseases would be the focus of the TCM inheritance and innovation development, which has been highly valued in recent years by the TCM academia and the relevant national management departments. Based on the clinical value, a series of policies are formulated for the selection and evaluation of the TCM dominant diseases (TCMDD), and exploratory researches about the clinical efficacy characteristics, the modern scientific connotation interpretation were carried out. The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed, which is characterized by strong policy support as the guarantee, systematic and standardized selection and evaluation methods as the driving force, scientific and effective research on internal mechanisms as the expansion, and effective clinical guidelines and principles as the transformation, which is of great value in promoting the high-quality development of the industries and undertaking of TCM. In this paper, the main policy support, selection and evaluation methods, therapeutic effect characterization, and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out, with a view to providing the healthy and benign development of the research on TCMDD.

OBJECTIVE To explore the effects of Yupingfeng granules on the improvement of epithelial barrier function and the inhibition of tumor metastasis by regulating epithelial-mesenchymal transition （EMT）. METHODS Thirty C57BL/6 mice were randomly divided into the normal group （distilled water），model group （distilled water） and Yupingfeng granule group （40 g/kg）， with 10 mice in each group. The model group and Yupingfeng granule group were inoculated with Lewis lung cancer cells subcutaneously in the right armpit to induce the spontaneous lung metastasis model. After modeling，each group was given water/ relevant medicine intragastrically，once a day，for 15 consecutive days. The effects of Yupingfeng granules on tumor metastasis were investigated by observing or determining the pathomorphology of lung tissue，metastatic lesion count on the surface of the lung， tumor metastatic lesion and the expression of carcinoembryonic antigens. qRT-PCR and Western blot assay were used to detect the mRNA and protein expressions of β-catenin，E-cadherin and vimentin in the lung tissue of mice. RESULTS Compared with the model group，the total number of pulmonary metastases on the surface was decreased significantly in Yupingfeng granule group （P＜ 0.05），the general morphology of lung tissue was recovered，and the expression of carcinoembryonic antigen in lung tissue was significantly decreased （P＜0.05）. mRNA and protein expressions of E-cadherin in lung tissue were significantly increased （P＜ 0.05），while mRNA and protein expressions of vimentin and β-catenin were significantly decreased （P＜0.05）. CONCLUSIONS Yupingfeng granules can inhibit EMT by regulating the expression of β-catenin，thus improving epithelial barrier function，and inhibiting the ability of tumor cells to invade and metastasize.

Objective:To develop a national secondary reference material of Urea and Creatinine in frozen human serum as a standard for metrological traceability.Methods:According to JJF1343-2012 "General and Statistical Principles for Characterization of Reference Materials" and JJF 1006-1994 " Technical Norm of Primary Reference Material ", the homogeneity, stability, and commutability were evaluated;Using the JCTLM recommended methods, the value of the reference materials was assigned through collaboration with 6 accredited reference laboratories from Guangdong Provincial Hospital of Chinese Medicine, Beijing Aerospace General Hospital, Shenzhen Mindray Bio-Medical Electronics, Maccura Biotechnology, Beijing Leadman Biochemistry, and Zhejiang MedicalSystem Biotechnology. Uncertainty components including inhomogeneity, stability and value assignment were evaluated.Results:The results of one-way analysis of variance of homogeneity for the reference materials showed P>0.05, and the stability evaluation was less than the critical value of the t-test. The measured values were in the 95% confidence interval in the four conventional detection systems for commutability, and the certified values and expanded uncertainties were urea:(14.7±0.3) mmol/L ( k=2),Cr:(313.9±14.5) μmol/L ( k=2). Conclusion:The prepared secondary reference materials of urea and creatinine had promising homogeneity, stability, and commutable, the values of urea and creatinine concentration in reference materials were accurate and reliable.

Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.

Aim Toresearchthemolecularmecha-nisms of adriamycin-induced cardiomyocyte apoptosis based on β-adrenoceptor signaling pathway during de-velopmentofheartfailure.Methods SeventymaleSD rats were assigned randomly into two groups:the con-trol group(CON,n=30)and the ADR-induced cardio-toxicity group (ADR,n =40 ).ADR was administered intraperitoneally in five equal injections (each contai-ning 3 mg·kg-1 )over a period of two weeks,with a total cumulative dose of 15 mg · kg-1 body weight. Age-matched rats injected with saline were used as controls.The general condition of all rats was observed, and transthoracic echocardiography was performed im-mediately following the final ADR injection,and then every other week.Serum and myocardial tissue were harvested at W2,W4 and W6 separately.The serum contents of brain natriuretic peptide(BNP)and cardiac troponin-T(cTn-T)were analyzed by euzymelinked im-munosorbent assay (ELISA ).The pathological change and apoptosis were determined by HE,Masson and ter-minal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL).The protein expressions ofβ1-AR,β2-AR,PKA and CaMK Ⅱ were detectedbyWesternblot.Results FollowingthefinalADRin-jection,cardiac systolic function and SV declined, which was accompanied by marked atrophy of the heart,low levels of cardiomyocyte fibrosis and apopto-sis,significantly increased serum BNP and cTn-T and decreased β1-AR,PKA and CaMK Ⅱ protein expres-sion.However,cardiac systolic function was improved with the extension of time but remained depressed as compared to CON group.The serum BNP and cTn-T concentration kept on rising.The gradual aggravation apoptosis and concomitant fibrosis in the ADR group heart were observed following ADR withdrawal.β1-AR protein expression was continuously down-regulated,β2-AR protein expression unchanged.Expression of PKA and CaMKⅡ proteins in hearts from ADR-injec-ted rats gradually increased.Conclusion β-AR/PKA/CaMKⅡ signaling pathway mediates cardiomyo-cyte apoptosis during the progress of ADR-induced car-diac dysfunction and pathological remodeling and apop-tosis.

We systematically analyse and summarize on the literature(1996-2016) by reading and analysing them.Active ingredients and pharmacological activity of traditional Chinese medicine pigment composition(Saffower Yellower Injection) is introduced and its response characteristics, factors and potential causes of ADR are revealed, which provides the reference for safe, rational clinical management of drugs.Also it reminds that clinicians should master the characteristics of adverse reactions of traditional Chinese medicine pigment and grasp the ADR potential causes and control measures, in order to reach the goal of rational drug use.

Objective To investigate the effects of salvianolate lyophilized injection(SLI) on neural functional recovery and the expression of microtubule associated protein-2(MAP2) after focal cerebral ischemia-reperfusion injury in the diabetic rats.Methods Diabetes model was made by intraperitoneal injection of streptozotocin (STZ) and cerebral ischemia-reperfusion model was developed by Longa suture occluded method in the middle cerebral artery of diabetic rats.The rats were randomly divided into five groups: sham operation group, model group, SLI (21.0 mg.kg-1,10.5 mg.kg-1) treatment groups, and edaravone (6 mg.kg-1) treatment group.3 hours after ischemia,rats were respectively given normal saline or drugs followed by the injection once a day for 14 days and the neurological impairment was assessed.2 h after the last injection,the rats were decapitated and the brains were collected.The expression of MAP2 protein and mRNA in the bilateral hippocampal ischemia and infarcted area was detected with immunohistochemistry and RT-PCR.Results Severe neurological dysfunction was found in diabetic rats that had been subjected to cerebral ischemic injury (1.850±0.457).A significant improvement on neurological function was found in the SLI treatment groups (1.581 ± 0.314, 1.345 ± 0.425) compared with model group(P＜0.01, P＜0.05).Moreover,the expression of MAP2 in ischemia bilateral hippocampal CA1 and penumbra was represented by the average optical density value respectively (0.743±0.250,0.561± 0.224).In the hippocampal CA1 region, the number of MAP2-positive cells (0.781 ± 0.420 , 0.851 ± 0.136) in the treatment group showed significant increase than those in model group (P＜0.01, P＜0.05).In the ischemic penumbra region,the number of MAP2-positive cells (0.753±0.235,1.203±0.326) in the treatment group showed significant increase than those in model group (P＜0.01, P＜0.05).Conclusion The SLI can promote the post-injury neurocognitive function in diabetic rats.The increase of MAP2 expression may be involved in the mechanisms.