ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.

OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (for unblocking the obstruction in the governor vessel and regulating the spirit) on depression-like behavior and the hippocampal Endophilin A1/reactive oxygen species (ROS) pathway in the chronic unpredictable mild stress (CUMS) model rats, and explore the mechanism of this therapy for depression. METHODS: Forty-eight male SD rats of SPF grade were randomly divided into a normal group (n=12) and a modeling group (n=36). In the modeling group, CUMS was performed to establish depression model. The successfully-modeled rats were randomized into a model group, a Tongdu Tiaoshen acupuncture group (referred to as the acupuncture group), and a fluoxetine group, with 12 rats in each group. In the acupuncture group, "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14) were stimulated with acupuncture. This intervention measure was delivered once a day, continuously for 6 days; it was discontinued on day 7 and was completed in 28 days. In the fluoxetine group, intragastric administration was done with fluoxetine solution (2.1 mg/kg), once a day, and for 28 consecutive days. Before and after modeling, and after intervention completion, the body mass, sucrose preference rate and the total distance of movement and the boxes of horizontal crossing in the open field experiment were observed in each group. After intervention, using HE staining, the hippocampal neuron morphology was observed; using Nissl staining, the hippocampal Nissl body number was counted. The hippocampal mitochondria was observed under transmission electron microscopy. The average fluorescence intensity of ROS in hippocampal was determined using flow cytometry. With Western blot method, the protein expression of Endophilin A1, growth associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF) in hippocampal was detected; and with RT-qPCR method, the mRNA expression of Endophilin A1, GAP-43, and BDNF was recorded. Using the immunofluorescence, the average fluorescence intensity of Endophilin A1, GAP-43, and BDNF in hippocampal tissue was determined. RESULTS: Compared with the normal group, in the model group, the body mass, sucrose preference rate, and the total distance of movement and the boxes of horizontal crossing in the open field experiment decreased (P<0.01); the hippocampal neuronal structure was unclear, the matrix was relatively loose, and the number of Nissl body decreased (P<0.01); mitochondrial structure was disarranged, the outer membrane was ruptured, mitochondrial cristae was irregular or missed; the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue increased (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and its average fluorescence intensity decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in body mass, sucrose preference rate, the total distance of movement and the boxes of horizontal crossing in the open field experiment (P<0.05, P<0.01); the hippocampal neuronal structure became relatively clear, the matrix was relatively dense, and the number of Nissl body was elevated (P<0.01); mitochondrial structure got normal and disarranged slightly, the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue were reduced (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and the average fluorescence intensity rose (P<0.01, P<0.05). Compared with the fluoxetine group, the acupuncture group presented the increase in the average fluorescence intensity of ROS, the protein expression and the average fluorescence intensity of Endophilin A1, the protein expression of GAP-43 and the mRNA expression of BDNF (P<0.01, P<0.05), and the decrease of the protein expression and the average fluorescence intensity of BDNF, the mRNA expression of Endophilin A1, and the average fluorescence intensity of GAP-43 (P<0.01, P<0.05). CONCLUSION Tongdu tiaoshen acupuncture alleviates depression-like behaviors in CUMS model rats and protects hippocampal neurons, which may be related to suppressing Endophilin A1/ROS signaling pathway and attenuating oxidative stress reactions.
Animals ; Male ; Hippocampus/metabolism* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Depression/psychology* ; Humans ; Reactive Oxygen Species/metabolism* ; Disease Models, Animal ; Acupuncture Points

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

Objective To explore the diagnostic value of alkaline phosphatase on the surface membrane of neutrophils(mNAP)in bloodstream infections(BSI)of Gram-negative bacteria(GNB)and Gram-positive bacteria(GPB).Methods A total of 418 patients diagnosed with BSI at Donghai People's Hospital from January 2022 to December 2023 were enrolled in the study.Based on the results of Gram staining from positive blood cultures,the patients were divided into GNB bacteremia(n=329)and GPB bacteremia(n=89).Additionally,35 hospitalized patients with systemic inflammatory response syndrome(SIRS)during the same period were selected as the control group.Their clinical data,routine laboratory test results,blood cultures and venous blood samples were collected,and the expression levels of mNAP were detected by flow cytometry.The receiver operating characteristics(ROC)curve was used to evaluate the diagnostic performance of mNAP for BSI of GNB and GPB.Results The expression levels of mNAP in the GPB infection,GNB infection and SIRS groups were 9 588(5 677,11 343)AB/C,16 616(11 853,22 035)AB/C,and 5 738(2 613,9 178)AB/C,respectively,and the difference among them was statistically significant(H=43.95,P＜0.000 1).Further pairwise comparisons showed that the expression levels of mNAP in the GNB infection group were significantly higher than those in the GPB infection group(U=203.0,P＜0.000 1)and the SIRS group(U=445.0,P＜0.000 1).Meanwhile,the expression levels of mNAP in the GPB infection group were significantly higher than that in the SIRS group(U=583.0,P＜0.000 1).The area under the ROC curve(AUCROC)of mNAP for predicting the BSI of GNB was 0.91(95%CI:0.85-0.96).When the cut-off value was 10 820 AB/C,its sensitivity and spe-cificity were 80.00%and 88.57%,respectively.The AUCROC of mNAP for predicting the BSI of GPB was 0.69(95%CI:0.55-0.83).When the cut-off value was 10 859 AB/C,its sensitivity and specificity were 33.00%and 88.13%,respectively.Conclusion The di-agnostic efficiency of mNAP for the BSI of GNB is significantly higher than that for the BSI of GPB,which may become a novel biologi-cal marker for distinguishing the BSI of GNB and GPB.

Lipid and glucose metabolism play crucial roles in maintaining energy homeostasis, and their dysregulation can lead to the development of metabolic disorders, such as obesity and diabetes. Studies indicate that the skeleton, involved in lipid and glucose metabolism, functions as an endocrine organ, regulating systemic metabolism through bone-derived molecules. Sclerostin is a protein mainly produced by osteocytes, possessing the ability to inhibit bone formation, and its antibodies have become therapeutic targets for treating osteoporosis. Recent evidence suggests that sclerostin also plays a role in lipid and glucose metabolism disorders. Therefore, through summarizing in vitro and in vivo researches, this article reviews the role of sclerostin in lipid and glucose metabolism, its relationship with obesity and diabetes, and potential role in the treatment of metabolic diseases in the future.

Objective:To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease (CKD) patients, and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia.Methods:It was a single-centre cross-sectional study. The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively. The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin. The anthropometric data such as height, weight, upper arm circumference, upper arm muscle circumference, skinfold thickness, pinch strength and handgrip strength were measured. Body composition analyzer was used to measure the body composition. The patients were divided into CKD stage 1-3 group, CKD stage 4-5 group, and stage 5 hemodialysis group. One-way ANOVA, Kruskal-Wallis H test, and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD. Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients. Results:The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients, with age of (61.8±13.7) years old and 114 males (54.8%). There were 89 patients (42.8%) with diabetic nephropathy and 67 patients (32.2%) with sarcopenia. As renal injury progressed, serum sclerostin levels were 0.4 (0.3, 0.9) ng/L, 0.5 (0.3, 1.1) ng/L, and 1.1 (0.6, 2.3) ng/L in patients with CKD stage 1-3, stage 4-5, and stage 5 undergoing hemodialysis ( χ2=8.934, P<0.001), and the prevalence of sarcopenia was 16.4% (10/61), 34.9% (15/43), and 40.4% (42/104) ( χ2=10.312, P=0.006), respectively. Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate ( r=-0.314, P<0.001), pinch strength ( r=-0.229, P=0.007), skinfold thickness ( r=-0.254, P<0.001), appendicular skeletal muscle index ( r=-0.169, P=0.010), body cell mass ( r=-0.174, P=0.020), and phase angle ( r=-0.264, P<0.001), and positively correlated with serum phosphorus ( r=0.227, P=0.002) and intact parathyroid hormone ( r=0.297, P<0.001). Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index] was negatively correlated with male ( β=0.330, t=5.675, P<0.001) and serum sclerostin ( β=-0.125, t=-2.143, P=0.033), and positively correlated with body mass index ( β=0.474, t=8.090, P<0.001). Conclusion:Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.

Interpretation of syndrome differentiation is a necessary topic for the research on intelligent syndrome differentiation. The syndrome differentiation system of traditional Chinese medicine （TCM） is huge， with diverse and interrelated interpretations， and non-standardized linguistic expressions， while detailed interpretations involve complex basic theories and literature of TCM， resulting in a challenging organization of the system. From the perspective of text mining， this article analyzed the limitations of existing intelligent syndrome differentiation research， clarified the importance and necessity of constructing a syndrome differentiation interpretation system， and proposed the idea of constructing an interpretation system including conceptual system， logical system， evaluation system， and visualization presentation. Future research can continue to refine the structure， logical and semantic relationships， as well as evaluation methods of the interpretation system based on this ideas， present concrete examples， and build the interpretation corpus by utilizing various data sources such as textbooks， medical records， medical discourse， and papers， to provide technicians with standard reference and data support for TCM syndrome differentiation interpretation.

OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）. CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.