This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

Objective To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children.Methods A retrospective analysis was performed on 23 chil-dren with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation(arthrography with elastic nail group)from January 2019 to December 2022,including 12 males and 11 fe-males,aged from 2 to 12 years old with an average of(7.36±1.89)years old;According to Judet fracture types,14 children were type Ⅲ and 9 children were type Ⅳ.In addition,23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation(elastic nail group),including 11 males and 12 females,aged from 2 to 14 years old with an average of(7.50±1.91)years old;Judet classi-fication included 15 children were type Ⅲ and 8 children were type Ⅳ.Operative time and intraoperative fluoroscopy times were compared between two groups.Metaizeau evaluation criteria was used to evaluate fracture reduction,and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups.Results Both groups were followed up for 12 to 24 months with an average of(16.56±6.34)months.Operative time and intraoperative fluoroscopy times of elastic nail group were(56.64±19.27)min and(21.13±7.87)times,while those of joint angiography with elastic nail group were(40.33±1 1.50)min and(12.10±3.52)times;there were difference between two groups(P＜0.05).According to Metaizeau evaluation,11 patients got excellent result,9 good and 3 fair in joint angiography with elastic nail group,while in elastic nail group,5 ex-cellent,13 good,4 acceptable,and 1 poor;the difference between two groups was statistically significant(P＜0.05).According to Tibone-Stoltz criteria,14 patients got excellent result,8 good,and 1 fair in joint arthrography with elastic nail group;while in elastic nail group,12 patients got excellent result,9 good,1 fair and 1 poor;there was no significant difference between two groups(P＞0.05).Conclusion Compared to percutaneous elastic intramedullary nail fixation,closed reduction assisted by arthrography has advantages of reduced operation time,decreased intraoperative fluoroscopy frequency,and improved fracture reduction.Arthrography enables clear visualization of the anatomical structures of radius,head,neck,bone,and cartilage in children,facilitating comprehensive display of fracture reduction and brachioradial joint alignment.This technique more pre-cisely guides the depth of elastic intramedullary nail implantation in radius neck,thereby enhancing surgical efficiency and success rate.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective:To investigate the predictive value of stone composition prediction method based on dual-source stone energy spectrum CT for uric acid stones.Methods:The clinical data of 204 patients with urinary stones, 159 males and 45 females, admitted to Shanghai Sixth People's Hospital from July 2020 to July 2022 were retrospectively analyzed. The average age was (50.7±14.3) years. There were 187 cases of upper urinary tract (kidney, ureter) stones and 17 cases of lower urinary tract (bladder, urethra) stones. All patients underwent preoperative dual-source stone energy spectroscopy CT, measuring CT values at 150 kV and 100 kV, respectively, and the calculated dual energy ratio (Ratio) was used to predict stone composition. Of the 204 cases in this group, 33 cases underwent percutaneous nephrolithotomy and 171 cases underwent ureteroscopic lithotripsy. Postoperative stone specimens were analyzed for stone composition by infrared spectroscopy. Subject work characteristic (ROC) curves were used to analyze the efficacy of preoperative dual-source stone energy spectrum CT to predict uric acid stones.Results:In 204 patients, preoperative CT predicted 28 cases of uric acid stones and 176 cases of non-uric acid stones, including 136 cases of calcium oxalate stones, 38 cases of hydroxyapatite, and 2 cases of cystine stones. Postoperative IR spectral analysis detected 26 cases of uric acid stones and 178 cases of non-uric acid stones, including 129 cases of calcium oxalate stones, 47 cases of hydroxyapatite, and 2 cases of cystine stones. Compared with the preoperative CT results, there were 2 false positives and no false negatives in the classification of uric acid stones. The ROC curve showed that the sensitivity of the CT value for predicting uric acid stones at 100 kV was 96.2%, the specificity was 99.5%, and the area under the ROC curve (AUC) was 0.995, with the best prediction value of 620 HU.The sensitivity of the CT value for predicting uric acid stones at 150 kV was 96.2%, specificity was 85.5%, AUC was 0.916, and the best predictive value was 597.5 HU. The sensitivity of using Ratio values for predicting uric acid stones was 100.0%, specificity was 97.9%, AUC was 0.996, and the best predictive value was 1.14. The CT values for uric acid stones at 100 kV and 150 kV were (558.58±77.07) HU and (521.12±83.54) HU, CT values for calcium oxalate stones were (1 335.26±301.82) HU and (878.21±200.21) HU, CT values for hydroxyapatite were (1 104.09±203.61) HU and (710.38±178.44) HU, respectively.The CT values of cystine stones were (684.5±67.18) HU and (573.5±67.10) HU, respectively, and the differences between uric acid stones and other components were statistically significant ( P<0.01). The Ratio values of uric acid stones, calcium oxalate stones, hydroxyapatite, and cystine stones were 1.08±0.06, 1.52±0.08, 1.62±0.40, and 1.19±0.02, respectively, and the differences were statistically significant ( P<0.01) when comparing uric acid stones with other components. Conclusion:The CT and Ratio values of dual-source stone energy spectrum CT can effectively distinguish uric acid stones from other types of stones, and the accuracy, sensitivity, and specificity of this method for predicting uric acid stones are high.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Objective To compare the measurement differences between the skull 3D printed model and the real specimen under different CT scan slice thicknesses, and to explore the effect of slice thickness on the accuracy of the 3D printed model. Methods Eight normal skull specimens (marked as Nos. f-8) (group N) were used for CT scanning with different slice thicknesses, specifically 0.625 mm (group A),1.25 mm (group B) , and 2.5mm (group C) ,3.75 mm (group D) , and 5 mm (group E) , and then earned out 3D reconstruction and 3D printing respectively, and compared the anatomical reduction degree of the foramen magnum diameter, anterior clinoid distance, and butterfly wing distance of the 3D printed skull model. Results The reduction degree of anatomical structure of 3D printed skull model decreased with the increase of CT slice thickness. There was no significant difference in the accuracy of 3D model among groups A, B and C (P >0.05 ) . There was a high correlation between group A, B and C and group N ( P < 0 .05 ).The size indexes and statistical values of group A, B and C were similar. Conclusion CT slice thickness has a significant effect on the accuracy and reduction of the 3D printed skull model. The 3D printed model with thin slice data (0.625 mm,1.25 mm,2.5 mm) has higher accuracy and less difference.

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
Biomarkers/metabolism* ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Spermatozoa/metabolism*