Diabetic peripheral neuropathy(DPN)is a common and devastating complication of diabetes,for which effective therapies are currently lacking.Disturbed energy status plays a crucial role in DPN pathogenesis.However,the integrated profile of energy metabolism,especially the central carbohy-drate metabolism,remains unclear in DPN.Here,we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry(HPIC-MS/MS)to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats.Furthermore,JinMaiTong(JMT),a traditional Chinese medicine(TCM)formula,was found to be effective for DPN,improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration.JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions,including excessive glycolysis restoration,tricarboxylic acid cycle improvement,and increased adenosine triphosphate(ATP)generation.Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions,which was remarkably corrected by JMT treatment.In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α).Our results expand the thera-peutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs,such as JMT,as an effective strategy for its treatment.

To investigate the protective effect of hirudin on kidneys of diabetic rats and its molecular mechanism.

Objective:To evaluate the therapeutic effects of Yufu ointment for acute radiation-induced skin injury. Methods:We enrolled a total of 104 patients with malignant tumors who developed acute skin injury of grade 2-3 during or after the first course of radiotherapy from June 2019 to February 2023. The observation group ( n=53) and control group ( n=51) received external application of Yufu ointment and Shirun Shaoshang ointment, respectively. We recorded the changes in the grade of skin injury and associated symptoms (such as pain, itching, and burning sensation) and healing speed and time for the two groups. Results:A total of 102 patients completed the study, with 53 cases in the observation group and 49 cases in the control group. The incidence rate of moisture skin lesions in the observation group was significantly lower than that in the control group (62.26% vs. 83.67%, P<0.05). The healing speed of moisture skin ulcerations was significantly faster in the observation group than in the control group (1.67 cm 2/d vs. 0.55 cm 2/d, P<0.05). The observation group had a significantly shorter time to skin injury healing than the control group (10.40 d vs. 14.41 d, P<0.05), significantly different for skin injury of grade 2 (10.21 d vs. 17.57 d, P<0.05) but not for skin injury of grades 2.5 and 3 ( P>0.05). Regarding clinical symptoms, both groups experienced significant reductions in pain and burning sensation scores after treatment ( P<0.05); the grade of itching was significantly decreased for the observation group ( P<0.05), but had no significant change for the control group after treatment ( P>0.05). Conclusions:Yufu ointment can significantly alleviate secondary damage for patients with acute radiation-induced skin injury, by accelerating the healing process and relieving symptoms such as pain, itching, and burning sensation with good tolerability, which deserves further promotion.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

To investigate the protective effect of hirudin on kidneys of diabetic rats and its molecular mechanism.

Objective:To evaluate the role of hippocampal β4-Subunit-Containing Nicotinic Acetylcholine Receptors (Chrnb4) in postoperative delirium in aged mice.Methods:Forty-eight SPF male C57BL/6J mice, aged 18 months, weighing 29-35 g, were assigned into 6 groups using a random number table method: tibial fracture group (TF group, n=6), sham operation group (Sham group, n=6), tibial fracture + adipenine group (TA group, n=9), tibial fracture + control vehicle group (TV group, n=9), sham operation + adipenine group (SA group, n=9), and sham operation + control vehicle group (SV group, n=9). The postoperative delirium model was prepared by tibial fracture under sevoflurane anesthesia. Tibial fracture was simulated by implanting a steel pin into the tibia and then clamping it, while sham group only received a longitudinal incision and suture after anesthesia. A microinjection cannula was implanted into the mouse skull at 5 days before developing the model in TA group, TV group, SA group and SV group. Three mice from each group were randomly selected for microelectrode implantation in the hippocampal CA1 area. Starting from 30 min after surgery, adipenine (62.5 nmol/μl) 2 μl was infused into the cerebral ventricle for 7 consecutive days in TA and SA groups, and vehicle (2 μl) was administered instead at a 24-h interval for 7 consecutive days in TV and SV groups. The expression of Chrnb4 mRNA in the hippocampal tissues was detected by real-time quantitative polymerase chain reaction at 24 h after surgery. On the 7th and 8th days after surgery, the open-field test and O-maze experiment were conducted to assess the impulsive-like behavior in TA, TV, SA and SV groups. After the behavioral test, the expression of glial fibrillary acidic protein (GFAP) and vesicular glutamate transporter 1 (Vglut1) in the hippocampal CA1 region was detected by immunofluorescence staining. The local field potentials in the hippocampal CA1 region were recorded during the open field test. Results:The expression of Chrnb4 mRNA in the hippocampal tissues was significantly up-regulated in TF group compared to Sham group ( P<0.05). Compared with TV group, the percentage of central path distance in the open field test and percentage of time spent in the open arms of the O-maze were significantly decreased, the power of β-waves in the CA1 field potentials was decreased, the expression of GFAP and Vglut1 in the hippocampal CA1 region was down-regulated, and the co-staining area of GFAP + and Vglut1 + was decreased in TA group and SV group ( P<0.05). There was no significant difference in each parameter between SA group and SV group ( P>0.05). Conclusions:Hippocampal Chrnb4 may be involved in the mechanism of postoperative delirium in aged mice, and this process may be related to inhibition of neuron excitotoxicity.

Objective:To explore the expression of endosialin, i.e., CD248 in human hypertrophic scars (HSs) and its regulatory effect on the phenotype of hypertrophic scar fibroblasts (HSFs).Methods:The method of experimental research was used. From March to May, 2023, 3 pediatric patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 2 females and 1 male, aged one year ten months to two years. The HS tissue resected during the surgery and the remaining full-thickness skin graft, i.e., normal skin tissue after full-thickness skin grafting were collected from the aforementioned pediatric patients for subsequent experiments. Using the aforementioned two types of tissue, the histological structures were observed by hematoxylin-eosin staining, collagen distribution was observed by Masson staining, and the expression of CD248 was observed and measured by immunohistochemical staining. The primary HSFs were isolated from HS tissue using explant culture technique, and the 3 rd to 5 th passages of HSFs were used in subsequent experiments. According to the random number table, HSFs were divided into immunoglobulin G78 (IgG78)-treated group and IgG control group, which were treated with 200 nmol/L human CD248 monoclonal antibody IgG78 and human IgG control antibody for 24 h, respectively. The mRNA expressions of collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) in HSFs were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the protein expressions of Col Ⅰ and α-SMA in HSFs were detected by Western blotting, and the intracellular location and protein expressions of Col Ⅰ and α-SMA were detected by immunofluorescence method. The number of samples in each experiment was 3. Data were statistically analyzed with paired sample t test and independent sample t test. Results:Compared with those in normal skin tissue, the epidermis and dermis in HS tissue were significantly thicker, with massive accumulation and disordered arrangement of collagen in the dermis. The expression of CD248 in HS tissue was significantly upregulated compared with that in normal skin tissue ( t=5.29, P<0.05). At post treatment hour 24, the mRNA expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.39±0.05 and 0.56±0.09, respectively, which were significantly lower than 1.00±0.07 and 1.00±0.08 in IgG control group, respectively (with t values of 11.87 and 6.49, respectively, P values all <0.05). The protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.617±0.011 and 0.67±0.14, respectively, which were significantly lower than 1.259±0.052 and 1.23±0.16 in IgG control group, respectively (with t values of 20.92 and 4.52, respectively, P values all <0.05). At post treatment hour 24, immunofluorescence staining showed that Col Ⅰ and α-SMA mainly located in the cytoplasm of HSFs in the two groups, and the protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were obviously downregulated compared with those in IgG control group. Conclusions:The expression of CD248 is significantly upregulated in human HS. Targeted blockade of CD248 can significantly inhibit the collagen synthesis by HSFs and the transdifferentiation of HSFs into myofibroblasts.

The ABRACL protein, the regulator of actin and cell motility, belongs to the HSPC280 family, and its conserved hydrophobic groove can interact with other proteins to facilitate actin motility and cellular activity. ABRACL is upregulated in tumor tissues and is closely linked with the proliferation and migration of tumor cells. A deeper understanding of the role of ABRACL in tumorigenesis and development may provide new ideas and insights for ABRACL to prevent or reverse tumor progression.

Objective:To investigate the effect of liraglutide(LRG) on high glucose-induced oxidative stress injury in(H9c2) cardiomyocytes and its underlying mechanisms.Methods:A high glucose treatment was applied to H9c2 cells for 24 hours to establish an in vitro model of myocardial cell injury. Different concentrations of liraglutide(10, 100, 1000 nmol/L) were administered for intervention. Cell viability was evaluated using the CCK-8 assay, and changes in cell morphology were observed under an inverted microscope. After 24 hours of liraglutide(100 nmol/L) intervention following high glucose treatment, the levels of lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) in the cell supernatant were measured. RT-PCR and Western blotting were used to detect the mRNA and protein levels of silent information regulator factor 1(SIRT1) and forkhead box protein O1(FOXO1). Western blotting was also used to assess the acetylation level of FOXO1 protein. Small interfering RNA(siRNA) technology was employed to silence SIRT1 in H9c2 cells to confirm its role in the study. Results:Compared to the control group, the high glucose group showed decreased cell viability, cell structure damage, increased levels of LDH and MDA in the cell supernatant, decreased SOD levels, aggravated oxidative stress, decreased SIRT1 expression, and increased acetylation level of FOXO1(all P<0.05). Compared to the high glucose group, liraglutide intervention resulted in increased cell viability, improved cardiac cell morphology, reduced oxidative stress levels, increased SIRT1 expression, and decreased acetylation level of FOXO1(all P<0.05). When SIRT1 was downregulated, the protective effects of liraglutide were weakened(all P<0.05). Conclusions:Liraglutide has a protective effect against high glucose-induced oxidative stress injury in H9c2 cells, which may be associated with the upregulation of SIRT1 expression.