Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

The aim of this study is to evaluate the in vitro and in vivo antibacterial potential of Ly-sZHSHW,a phage lysin against Acinetobacter baumannii infections,and to study its characteris-tics.The pET28a-Lys recombinant plasmid containing LysZHSHW coding gene was constructed by PCR,enzyme digestion and ligation using the expression plasmid pET28a as the backbone and ex-pressed in E.coli BL21(DE3).After confirming the expression of the LysZHSHW through West-ern blot analysis,its characterization and potential applications were assessed both in vitro and in vivo.The results showed that the pET28a-Lys recombinant plasmid was successfully constructed and the LysZHSHW protein was expressed correctly.The mass concentration of the purified en-zyme was 4 086 mg/L,which could be used for subsequent experiments.The enzymatic activity of LysZHSHW was determined to be 630 U/μg,with maximum activity observed at 25 ℃ and pH9.0.In vitro experiments demonstrated that 1 000 or 750 mg/L of LysZHSHW,in the presence of EDTA,resulted in a four-log reduction in bacterial counts without any cytotoxicity.In vivo,2.5 μg of LysZHSHW combined with EDTA could increase the survival rate of Galleria mellonel-la larvae infection model to 92.86％after 24 hours,and 0.15 mg of LysZHSHW reduced the bacte-rial load in the thighs of mice by 2.8 logs and alleviated the inflammatory response in muscle fi-bers.In conclusion,LysZHSHW derived from Acinetobacter baumannii bacteriophage exhibited characteristics such as stability at room temperature,alkaline pH,and safety,making it a promis-ing candidate as a novel antimicrobial agent.

OBJECTIVE To construct a clinical model of motion sickness(MS),provide a relatively objective diagnostic model for MS research,and provide a basis for further clinical intervention of the disease.METHODS A total of 60 subjects were included and divided into experimental group and control group according to the presence or absence of MS.The MS clinical model was established using SRM-IV rotating chair.Peripheral blood was collected before and after acceleration exposure,and the contents of adrenocorticotropic hormone(ACTH),growth hormone(GH),prolactin(PRL),follicle stimulating hormone(FSH),luteinizing hormone(LH),thyroid stimulating hormone(TRH)and gastrin-17(G-17),acetylcholine(ACH)and 5-hydroxytryptamine(5-HT)were detected,Graybiel scale was used to evaluate the severity of MS.The correlation between MS symptoms and signs and peripheral blood indexes was analyzed by multiple linear regression,and the diagnostic model was established.construct a clinical model of MS and a diagnostic model based on blood parameters,so as to provide a reliable clinical model and an objective diagnostic model for MS research,and to provide a basis for further clinical intervention of the disease.RESULTS After acceleration exposure,the Graybiel scores,ACH,5-HT,ACTH,GH and PRL levels in peripheral blood of the experimental group were higher than those before exposure,and were significantly different from those of the control group(P<0.001).There was no significant difference in FSH,LH,TRH and G-17 between the two groups before and after acceleration exposure(P>0.05).Multi-index combined diagnostic model:Graybiel scores=-9.32+0.131×ACTH+0.055×ACH+0.041×5-HT.CONCLUSION The levels of ACH,5-HT,ACTH,GH and PRL increased during the onset of MS.The multi-index combined diagnosis model can provide a certain basis for the objective diagnosis of MS in clinical practice.

Objective:To explore the effectiveness of body weight support in gait training after surgery for an ankle fracture.Methods:Thirty-eight ankle fracture patients who received surgery were divided at random into an observation group and a control group, each of 19. In addition to 3 sessions of routine gait rehabilitation training a week for 6 weeks, only those in the observation group received body weight support training with body weight support boots. Gait data were collected using the GaitWatch three-dimensional gait action capture and training system before the training and after 2, 4 and 6 weeks of the training.Results:At each assessment the gait frequency, gait cycle, stride length, stride rate, bilateral step length, step length deviation, bilateral support phase and bilateral swing phase of both groups had improved significantly. After 6 weeks the average stride frequency, gait cycle, stride length on both sides and speed of the observation group had improved significantly more than among the control group. Step length deviation was not significantly different, however. At each evaluation the proportions of affected and healthy side support had decreased significantly in both groups, but affected and healthy side swing had increased and the proportion of bilateral support had decreased significantly.Conclusion:Body weight support training with body weight support boots can significantly improve gait after ankle fracture surgery. Its effect is superior to that of conventional gait training.

Objective To construct and validate a risk prediction model for enteral nutrition feeding intolerance (FI) in patients with severe cerebral hemorrhage based on machine learning algorithms. Methods The clinical data of 485 patients with cerebral hemorrhage admitted to the neurological intensive care unit of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2020 to December 2022 were retrospectively analyzed. The patients were randomly divided into training set (n=339) and validation set (n=146) in a 7 to 3 ratio. Five machine learning algorithms were used to construct FI risk prediction models. The receiver operating characteristic (ROC) curve was plotted, and the model with the best predictive performance was selected based on the area under the curve (AUC). A nomogram model was constructed based on the optimal model. The calibration curve and decision curve analysis (DCA) were used to evaluate the calibration and clinical net benefit of the nomogram model. Results The incidence of enteral nutrition FI in patients with severe cerebral hemorrhage was 38.4%(186/485). Among the five machine learning algorithm models, the Logistic regression model had the best predictive performance(AUC=0.88). The analysis results of the Logistic regression model showed that the use of diuretics, mechanical ventilation, Glasgow Coma Scale score ≤5, vasoactive drugs, and albumin level<35 g/L were risk factors for enteral nutrition FI in patients with severe cerebral hemorrhage. A nomogram model was further constructed based on these five risk factors. The calibration curve analysis showed that the calibration curve fitted well with the ideal curve, indicating a high calibration degree of the nomogram model. The DCA results showed that when the threshold probability was 5% to 73%, the application of the nomogram model for screening could clinically benefit patients. Conclusion The construction of a nomogram model for predicting the risk of enteral nutrition FI in patients with severe cerebral hemorrhage based on machine learning methods can help to early screen high-risk patients for enteral nutrition FI and timely formulate preventive measures, thereby reducing the incidence of enteral nutrition FI in patients with severe cerebral hemorrhage.

Objective:To investigate the characteristics of digestive system symptoms and its relation with the time of nucleic acid continuous positive in population infected with severe acute respiratory syndrome coronavirus 2 Omicron variant, and to analyze the abdominal computed tomography (CT) features of patients infected with Omicron variant.Methods:From April 11 to May 23, 2022, a questionnaire survey was conducted in patients infected with Omicron variant admitted to the Shanghai National Convention and Exhibition Center Fangcang Hospital. The questionnaire included basic information, the start time of nucleic acid positive, respiratory symptoms, digestive system syptoms and outcomes, etc.Combined with the clinical data, the relation between digestive tract symptoms and the time of nucleic acid continuous positive were analyzed. Thoracic and abdominal CT were performed for patients with continuous positive nucleic acid results ≥10 d, and the relationship between the abdominal CT imaging characteristics and the time of nucleic acid continuous positive was analyzed. Independent sample t-test and multivariate logistic regression were used for statistical analysis. Results:A total of 4 360 valid questionnaires were collected, including 2 475 males and 1 885 females, with a hospital stay of (6.8±4.9) d. Among the 4 360 patients, 1 979 patients (45.4%) had gastrointestinal symptoms such as loss of appetite, abdominal discomfort or pain, constipation and diarrhea. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms was (7.4±5.5) d, which was longer than that of patients without gastrointestinal symptoms (6.5±3.6) d, and the difference was statistically significant ( t=3.78, P<0.001). During the isolation period in the Fangcang Hospital, the time of nucleic acid continuous positive in patients with complete remission of digestive tract symptoms was shorter than that of patients with no remission of digestive tract symptoms ((7.3±5.2) d vs. (8.5±5.7) d), and the difference was statistically significant ( t=2.25, P=0.025). The results of multivariate logistic regression analysis showed that the combination of gastrointestinal symptoms was an independent risk factor for continuous positive nucleic acid result ≥10 d ( OR=1.316, 95% confidence interval 1.294 to 2.205, P=0.046). Among the 299 patients with continuous positive nucleic acid results≥10 d, 187 cases (62.5%) had gastrointestinal symptoms, and 146 cases (48.8%) had abdominal CT findings of thickening of the gastroduodenal wall, thickening of the small intestinal wall, indistinct mesenteric vessels of the small intestine, and dilatation and pneumatosis of the colon. In patients with continuous positive nucleic acid results ≥10 d, abdominal CT indicated that patients with gastrointestinal imaging changes had a longer time of nucleic acid continuous positive than those without gastrointestinal imaging changes ((16.0±2.8) d vs. (13.0±2.1) d), and the difference was statistically significant ( t=2.62, P=0.009). Conclusions:Digestive system symptoms are common in patients infected with Omicron variant. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms is longer than those without gastrointestinal symptoms. Some patients may have gastrointestinal lesions on abdominal CT.

Objective:To investigate prognostic factors for acral lentiginous melanoma (ALM) , and to construct a nomogram to verify the predictive value of these factors.Methods:Clinical data on 1 573 patients with ALM were collected from the Surveillance, Epidemiology, and End Results (SEER) database of National Cancer Institute in United States between 2004 and 2015. Data about patients′ age, gender, ulcer status, SEER staging, surgical protocols, T-, N- and M-staging, overall survival rates and disease-specific survival rates were extracted. Chi-square test was used to analyze the correlation of clinical characteristics with overall survival rates and melanoma-specific survival rates, and univariate and multivariate Cox proportional hazards regression models were used to investigate prognostic factors and establish predictive models.Results:Among the 1 537 patients with ALM, 714 were males, 823 were females, 818 were under 64 years of age, and 1 363 were Caucasian. Skin lesions occurred on the lower limbs and buttocks in 1 205 cases, and 974 cases had ulcers; according to the SEER staging, non-spread localized skin lesions were observed in 1 048 cases. There were significant differences in the mortality rate among patients of different ages at diagnosis, different gender, with different ulcer status, surgical status, and at different SEER stages, T-stages, N-stages and M-stages (all P < 0.001) . Univariate and multivariate Cox regression analysis showed that age ≥ 65 years, male, ulcers and distant lymph node metastasis in the SEER staging were associated with increased risk of death in the patients (all P < 0.05) , and the mortality rate was significantly higher in the patients with T2-, T3- or T4-stage ALM than in those with T1-stage ALM (all P < 0.05) , and higher in the patients with N1-, N2- and N3-stage ALM than in those with N0-stage ALM (all P < 0.05) . Conclusion:Age, gender, ulcer status, SEER stage, T-stage and N-stage are independent prognostic factors for overall survival rates and disease-specific survival rates of ALM.

Objective:To explore the experience of the treatment of patella inferior pole fracture with non excitation tension band technique.Methods:From April 2009 to December 2019, 76 patients with inferior patellar fracture were treated with non excitation tension band technique. There were 42 males and 34 females; The age was 35.48 ± 18.12 years (17-66 years), with an average of 35 years. There were 45 cases on the left and 31 cases on the right. Causes of injury: fall injury in 46 cases, bicycle injury in 16 cases and traffic accident injury in 14 cases. The time from injury to operation was 0.25-5 d, with an average of 3.2 d. There were 18 cases of open fractures, 64 cases of articular surface fractures and 52 cases of comminuted fractures. Open fracture patients were debridement first, and all cases were fixed with non excitation tension band technique. The intraoperative fracture reduction, postoperative fracture healing and internal fixation were observed. The knee function was evaluated according to the degree of claudication, the use of supports, the feeling of joint strangulation, joint instability, pain, swelling, stair climbing and squatting.Results:All 76 patients successfully completed the operation and were followed up for 18.24 ± 6.18 months (range 12-24 months). There was no wire fracture during and after operation. All incisions healed in the first stage after operation, and there was no deep venous thrombosis of lower limbs. The X-ray film showed that there was no further fracture and fracture displacement after operation, and there was no Kirschner wire slip before the internal fixation was taken out. Only one case had steel wire relaxation due to buckle (which did not affect fracture healing). All fractures healed well, with an average of 7.5 weeks, and the fracture line basically disappeared. 12 months after operation, according to Lysholm knee score standard, the knee function of patients was evaluated. The score of 76 cases was 95.40±4.60 points (range 82-100 points): excellent in 54 cases, good in 21 cases and fair in 1 case. The excellent and good rate was 98.7%. According to the visual analogue scale (VAS) pain score standard, the patients were scored for postoperative pain. The score of 76 cases was 0.09±2.05 points (range 0-3 points): 4 cases had mild pain, with an average score of 0.09.Conclusion:The results of the treatment of patellar inferior pole fracture with tension free band technique are satisfactory, the pain caused by tissue irritation by the internal fixation was lower, clinical application can be popularized.