ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

Objective To explore the mechanism of Nuanxinkang Powder(aka.NXK,composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescens Radix)on improving ventricular remodeling in post-infarction mice based on the"metabolic-inflammatory"network regulating macrophage polarization.Methods ①Thirty C57BL/6J male mice were randomly divided into three groups:sham-operation group,model group,and NXK group(1.65 g·kg-1),with 10 mice in each group;the mouse model of myocardial infarction was replicated using left anterior descending coronary artery ligation;and the drug was administered by gavage once a day for 4 consecutive weeks.Masson staining was used to detect collagen deposition in myocardial tissue;ultrasound was used to detect cardiac function in mice:left ventricular ejection fraction(LVEF),left ventricular anterior wall thickness at end-systole(LVAWS)and left ventricular anterior wall thickness at end-diastole(LVAWD);flow cytometry was used to detect distribution of cardiac macrophages in mice;qPCR was used to detect mRNA expressions of lactate dehydrogenase A(LDHA),carnitine palmitoyltransferase 1(CPT-1),glucose transport protein 4(GLUT4),isocitrate dehydrogenase(IDH),and succinate dehydrogenase(SDHa)in heart tissue.②NXK was given 1.15 g·kg-1 NXK suspension to rats by gavage twice a day for 5 consecutive days to prepare NXK-containing serum.Lipopolysaccharide(LPS)-induced RAW 264.7 cells were used to construct a pro-inflammatory macrophage model.The cells were grouped into the following groups:blank serum control group(medium containing 5%blank serum+5%fetal bovine serum),NXK drug-containing serum group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum),lipopolysaccharide group(medium containing 5%blank serum+5%fetal bovine serum+200 μg·mL-1 lipopolysaccharide),NXK drug-containing serum+ lipopolysaccharide group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum+200 μ g·mL-1 lipopolysaccharide),all the groups were intervened for 16 hours.Glycolysis stress test was used to detect the level of glycolysis in RAW 264.7 cells;qPCR was used to detect the mRNA expression of mitochondrial pyruvate carrier(MPC1)in RAW 264.7 cells;and MitoSox Red fluorescent staining was used to detect the level of oxidative stress damage in mitochondria of RAW 264.7 cells.Results ①Compared with the sham-operation group,the blue-stained area of cardiac collagen fibres in mice of the model group was significantly increased,accompanied by thinning of the ventricular wall and enlargement of the left ventricular cavity;cardiac function indexes,such as LVEF,LVAWS,LVAWD,etc.,were all significantly reduced(P＜0.01,P＜0.001);the mRNA expressions of LDHA and CPT-1 were significantly up-regulated in the cardiac tissues of mice(P＜0.05),and the mRNA expressions of GLUT4,IDH and SDHa were significantly down-regulated(P＜0.05,P＜0.01),and CD86 staining positive cell was significantly increased(P＜0.001).Compared with the model group,mice in the NXK group showed a significant decrease in cardiac collagen fiber deposition and an increase in the thickness of the ventricular wall;cardiac function indexes such as LVEF,LVAWS and LVAWD were significantly increased(P＜0.05,P＜0.01,P＜0.001);and the mRNA expressions of LDHA and CPT-1 in the cardiac tissues of the mice were significantly down-regulated(P＜0.01,P＜0.001),mRNA expressions of GLUT4,SDHa and IDH were significantly up-regulated(P＜0.01),and the number of CD86 positive cells was significantly reduced(P＜0.001).②Compared with the blank serum control group,the cytosolic glycolysis level and ROS level of macrophages in the NXK serum-containing group did not change significantly(P＞0.05),whereas the glycolysis level and ROS level of macrophages in the lipopolysaccharide group were significantly increased(P＜0.01),and the mRNA expression of MPC1 was significantly down-regulated(P＜0.001).Compared with the lipopolysaccharide group,the macrophage glycolysis level and ROS level were significantly reduced in the NXK serum-containing + lipopolysaccharide group(P＜0.05,P＜0.01),and mRNA expression of MPC1 was significantly up-regulated(P＜0.001).Conclusion NXK can reduce myocardial fibrosis and ventricular remodeling after myocardial infarction and improve cardiac function in mice,and its mechanism may be related to the down-regulation of mRNA expression of LDHA in cardiac tissues,the up-regulation of mRNA expression of GLUT4,the improvement of cardiac glucose uptake after myocardial infarction,the inhibition of pro-inflammatory macrophage glycolysis,the increase in the expressions of SDHa and IDH to alleviate the accumulation of succinate and citrate,and the reduction of reactive oxygen species(ROS)generation,thereby reducing pro-inflammatory macrophage hyperpolarisation.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective:To establish a nomogram model for predicting the risk of sepsis in diabetic foot patients, and to provide reference for clinical prevention and treatment.Methods:The clinical data of 430 patients with diabetic foot who were hospitalized in Chu Hsien-I Memorial Hospital of Tianjin Medical University from January 2022 to March 2023 were reviewed and collected, including age, gender, past medical history, smoking and drinking history, family history, diabetes course, Texas grade of diabetic foot and laboratory indicators within 24 hours after admission. Patients were divided into sepsis group and non-sepsis group according to the presence or absence of sepsis during hospitalization. The differences in clinical data between the two groups were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of sepsis in patients with diabetic foot during hospitalization, and a nomogram predictive model was established. The performance of the prediction model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA). Internal validation was performed by using Bootstrap method.Results:A total of 430 patients were enrolled, among which 90 patients developed sepsis during hospitalization and 340 patients did not. There were statistically significant differences in diabetes course, Texas grade of diabetic foot, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil to lymphocyte ratio (NLR), hemoglobin (Hb), albumin (Alb), glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and blood urea nitrogen (BUN) between the two groups. Multivariate Logistic regression analysis showed that diabetes course [odds ratio ( OR) = 2.774, 95% confidence interval (95% CI) was 1.053-7.308, P = 0.039], Texas grade of diabetic foot ( OR = 2.312, 95% CI was 1.014-5.273, P = 0.046), WBC ( OR = 1.160, 95% CI was 1.042-1.291, P = 0.007), HbA1c ( OR = 1.510, 95% CI was 1.278-1.784, P < 0.001), CRP ( OR = 1.007, 95% CI was 1.000-1.014, P = 0.036) were independent risk factors for sepsis in patients with diabetic foot during hospitalization, while Alb was a protective factor ( OR = 0.885, 95% CI was 0.805-0.972, P = 0.011). A nomogram predictive model was constructed based on the above 6 indicators. The ROC curve showed that the area under ROC curve (AUC) of the nomogram predictive model for identifying the sepsis patients was 0.919 (95% CI was 0.889-0.948). The AUC of the nomogram predictive model after internal verification was 0.918 (95% CI was 0.887-0.946). Hosmer-Lemeshow test showed χ2 = 2.978, P = 0.936, indicating that the calibration degree of the predictive model was good. Calibration curve showed that the predicted probability of sepsis was in good agreement with the actual probability. DCA curve showed that the nomogram predictive model had good clinical usefulness. Conclusion:The nomogram predictive model based on the risk factors of diabetes course, Texas grade of diabetic foot, WBC, HbA1c, CRP and Alb has good predictive value for the occurrence of sepsis in patients with diabetic foot during hospitalization, which is helpful for clinical screening of the possibility of diabetic foot patients progressing to sepsis, and timely personalized intervention for different patients.

Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.

Objective:To investigate the effect of polypeptide N-acetylgalactosaminaminyltransferase 2 (GALNT2) on the proliferation and apoptosis of human retinal vascular endothelial cells (HRCECs) cultured in high glucose and its possible mechanism.Methods:The small hairpin RNA (shRNA) targeting GALNT2 gene was constructed to interfere with the lentiviral vector and infect HRCECs.HRCECs were divided into blank control group, model group, NC-shGALNT2 group and shGALNT2 group, which were cultured in medium containing 5.5 mmol/L glucose, 25 mmol/L glucose, shGALNT2 negative control virus 25 mmol/L glucose and shGALNT2 knockdown virus 25 mmol/L glucose for 24 hours, respectively.The relative expression of GALNT2 mRNA in the four groups was detected by real-time fluorescence quantitative PCR.The relative expression levels of GALNT2, epidermal growth factor (EGF), EGF receptor (EGFR) and phosphorylated EGFR (p-EGFR) were detected by Western blot.The proliferative values of HRCECs were detected by cell counting kit-8 method.The apoptosis rate of different groups was detected by flow cytometry. Results:The relative expression levels of GALNT2 mRNA and protein were significantly higher in model group than in blank control group, and were significantly lower in shGALNT2 group than in blank control group (all at P<0.05). The cell proliferation value was significantly lower in model group than in blank control group, and was significantly higher in shGALNT2 than in model group and NC-shGALNT2 group (all at P<0.05). The apoptosis rates of blank control group, model group, NC-shGALNT2 group and shGALNT2 group were (4.73±0.26)%, (8.66±0.25)%, (9.26±1.12)% and (5.47±0.18)%, respectively, with a significant overall difference ( F=342.921, P<0.001). The apoptosis rate was significantly higher in model group than in blank control group, and was significantly lower in shGALNT2 group than in model group and NC-shGALNT2 group (all at P<0.05). The relative expression level of EGFR protein was significantly higher and the relative expression level of p-EGFR protein was significantly lower in model group than in blank control group (all at P<0.05). The relative expression of p-EGFR protein was significantly higher in shGALNT2 group than in model group (all at P<0.05). Conclusions:Knocking down GALNT2 can improve the proliferative ability of HRCECs under high glucose culture and reduce apoptosis, which may be related to the activation of EGFR signaling pathway.

Objective:To explore the risk factors for hemophagocytic syndrome (HPS) in childhood Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM).Methods:From January 2013 to December 2017, the medical charts of all children who were diagnosed with EBV-associated IM and HPS in Children′s Hospital of Soochow University were analyzed retrospectively. Statistical analyses were performed using SPSS version 22.0.Results:A total of 316 IM and 59 HPS were enrolled. The age was (4.26 ± 2.95) years old with a male-to-female ratio of 1.2∶1. In addition to the diagnostic criteria of HPS, there were significantly lower rates of fever >10 d, hepatomegaly, jaundice, alanine aminotransferase >500 U/L, aspartate aminotransferase >500 U/L, LDH >1 000 U/L, C-reactive protein >50 mg/L and hypoalbuminemia in children with EBV-associated IM compared to those with HPS, and the differences were statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that fever >10 d, eyelid edema, lymphadenopathy and purulent tonsils were independent predictors of HPS in children with EBV-associated IM ( P<0.05). Hepatomegaly and fever >10 d were risk factors ( OR = 16.079 and 12.138, 95% CI 2.788 to 92.744 and 2.878 to 51.180). Eyelid edema, lymphadenopathy and purulent tonsils were protective factors ( OR = 0.087, 0.006 and 0.031; 95% CI 0.010 to 0.723, 0.001 to 0.058 and 0.007 to 0.146). Conclusions:Hepatomegaly and fever >10 d are the risk factors for hemophagocytic syndrome in childhood EBV-associated infectious mononucleosis.

Objective: To explore the relationship between selenium and the risk for oral cancer. Methods: We performed a case-control study in 325 cases of newly diagnosed primary oral cancer from the First Affiliated Hospital of Fujian Medical University and 650 controls from the same hospital and community. Unconditional logistic regression and stratification analyses were used to explore the association between selenium and oral cancer. Adjusted OR and corresponding 95%CI were calculated. The analyses on multiple interactions between selenium and smoking or drinking status, and fruit or fish intake frequencies were conducted. Results: The level of serum selenium was 112.42 (80.98-145.06) μg/L in the case group, which was lower than 164.85 (144.44-188.53) μg/L in control group, the difference was statistical significant (P<0.01). There was a negative correlation between serum selenium level and the risk for oral cancer regardless of smoking and drinking status, and fruits and fish intake frequencies (P<0.05). There were multiple interactions between serum selenium level and smoking or drinking status, and fruit and fish intakes. Conclusions The high level of serum selenium is a protective factor for the incidence of oral cancer, and serum selenium has multiple interactions with smoking or drinking status, and fruit and fish intakes. Therefore, reducing tobacco use and alcohol consumption and increasing the intakes of fruit and fish can reduce the risk for oral cancer to some extent.

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (β=-0.405, P<0.001). Conclusion This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

Objective To explore the association of TBX 5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods A case?control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non?tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56± 12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co?dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene?environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (β=-0.405, P<0.001). Conclusion This study suggests that the TBX 5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.