This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

OBJECTIVE: To explore the effectiveness of free paraumbilical perforator flaps in repairing skin and soft tissue defects in children. METHODS: Between February 2018 and March 2024, 12 children with skin and soft tissue defects were treated with the free paraumbilical perforator flaps. There were 7 boys and 5 girls with an average age of 6.3 years (range, 2-12 years). The defects located on the upper limbs in 6 cases, lower limbs in 5 cases, and neck in 1 case. The causes of wounds included 7 cases of electrical burns, 1 case of thermal burn, 2 cases of scar release and excision due to scar contraction after burns, 1 case of scar ulcer at the amputation stump after severe burns, and 1 case of skin necrosis after a traffic accident injury. The size of defects after debridement ranged from 7.0 cm×4.0 cm to 18.0 cm×10.0 cm. According to the defect size, 11 cases were repaired with unilateral paraumbilical perforator flaps centered on the umbilicus, among which 3 cases with larger defects were designed as "L"-shaped flaps along the lateral and lower ends of the perforator; the donor sites were directly closed. One case with extensive defect after scar excision and release was repaired with bilateral expanded paraumbilical perforator flaps; the donor sites were repaired with autologous split-thickness skin grafts. The size of flaps ranged from 9.0 cm×4.0 cm to 20.0 cm×11.0 cm. Postoperatively, analgesia and sedation were provided, and the blood supply of the flaps was observed. RESULTS: All operations were successfully completed. The operation time was 4-7 hours, with an average of 5.0 hours. After postoperative analgesia and sedation, the visual analogue scale (VAS) score for pain in all children was less than or equal to 3, and there was no non-cooperation due to pain. All flaps and skin grafts survived completely, and the wounds healed by first intention. Ten children underwent 1-4 times of flap de-fatting, finger separation, and trimming. All children were followed up 6-48 months (mean, 26.6 months). No obvious swelling of the flaps occurred, and the texture was soft. At last follow-up, among the 6 children with upper limb defects, 2 had upper limb function grade Ⅳ and 4 had upper limb function grade Ⅴ according to the Carroll upper limb function assessment method. The 4 children with lower limb defects had no limitation of joint movement. The neck flexion and rotation in the 1 child with neck defect significantly improved when compared with that before operation. The 1 child with residual ulcer at the amputation stump could wear a prosthesis and move without limitation, and no new ulcer occurred. Linear scars were left at the donor sites, and no abdominal wall hernia was formed. CONCLUSION The free paraumbilical perforator flap has abundant blood supply and can be harvested in large size. It can be used to repair skin and soft tissue defects in children and has the advantages of short operation time, minimal injury, high safety, and minimal impact on the growth and development of children.
Humans ; Perforator Flap/transplantation* ; Child ; Male ; Female ; Soft Tissue Injuries/surgery* ; Child, Preschool ; Plastic Surgery Procedures/methods* ; Burns/surgery* ; Umbilicus/surgery* ; Skin Transplantation/methods* ; Skin/injuries* ; Cicatrix/surgery* ; Treatment Outcome

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective To analyze the characteristics of methadone-related poisoning cases and provide a reference for forensic identification.Methods A total of 71 cases of methadone-related poisoning re-ported from 1998 to 2023 in China and 26 cases of methadone-related deaths reported from 2013 to 2018 in Italy were retrieved from databases including PubMed,Wanfang and CNKI.The general infor-mation,forensic pathological and toxicological characteristics were analyzed.Results Among the 71 methadone-related poisoning cases in China,there were 54 cases(76.06%)of poisoning without death and 17 cases(23.94%)of death from poisoning.There were 54 male cases(76.06%),and 51 cases(71.83%)aged 19 to 39 years old.There were 35 cases(49.30%)of poisoning caused by methadone alone,and 32 cases(45.07%)were poisoning caused by methadone combined with other substances or drugs including heroin and benzodiazepines.Most of the poisoned showed coma,respiratory depres-sion and miosis.Signs of asphyxia were often found by autopsy.The mass concentration of methadone detected in the blood of 6 deceased ranged from 0.112 to 3.000 mg/L.Among the 26 methadone-related deaths in Italy,22 cases were male(84.62%).There were 6 cases(23.08%)caused by methadone alone,and 20 cases(76.92%)died from methadone combined with other substances or drugs.The mass concentration of methadone in blood ranged from 0.181 to 4.059 mg/L.Conclusion The propor-tions of poisoning cases caused by methadone alone and methadone combined with other substances or drugs are comparable in China.The majority of deceased caused by methadone poisoning shows typi-cal triad of coma,respiratory depression and miosis,which helps forensic experts determine the cause of death related to methadone.Additionally,it is necessary to increase the routine testing of the con-centration of methadone and its combined substances or drugs in deceased,and collect data for the in-terpretation of the results of related cases.

Objective To explore the risk factors for 28-day mortality of sepsis-associated acute kidney injury(SA-AKI)patients and to develop a nomogram risk prediction model.Methods A retrospective cohort study was conducted,involving 184 patients with SA-AKI admitted to the intensive care unit(ICU)of the 940th Hospital of Joint Logistic Support Force of PLA between January 2017 and December 2022.Patients were categorized into survival(n=135)and non-survival(n=49)groups based on 28-day mortality.Clinical data were collected,and statistically significant risk factors were preliminarily screened.Multivariate stepwise logistic regression analysis was performed to identify independent risk factors for 28-day mortality of SA-AKI patients.A nomogram predictive model was constructed using these factors,and internally validated with the Bootstrap method.The receiver operating characteristic curve(ROC curve)was drawn,and the area under the ROC curve(AUC)was calculated to verify the predictive value and accuracy of the model.Results The 28-day mortality rate among 184 SA-AKI patients was 26.6％(49/184).Multivariate stepwise logistic regression analysis identified multiple organ dysfunction syndrome(MODS)(OR=16.393,95％CI 4.317-62.254,P＜0.001),high acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(OR=1.097,95％CI 1.036-1.161,P=0.002),low oxygenation index(OR=0.992,95％CI 0.986-0.998,P=0.015),low neutrophil count(OR=0.912,95％CI 0.860-0.968,P=0.002)and low fibrinogen concentration(OR=0.733,95％CI 0.549-0.978,P=0.034)as independent risk factors.The prediction model equation was P=1/1+e-logit(P),logit(P)=-1.626+2.797×MODS+0.092×AP ACHE Ⅱ+(-0.311)×fibrinogen+(-0.092)×neutrophil count+(-0.008)×oxygenation index.Internal validation with 1000 Bootstrap resamples showed high consistency between predicted and actual values.ROC analysis showed an AUC of 0.911(95％CI 0.868-0.955,P＜0.05)for the model,with 93.9％sensitivity and 78.5％specificity at a cut-off of 0.194.The Hosmer-Lemeshow test confirmed good calibration(P=0.62),and decision-making curve analysis demonstrated clinical utility within the high-risk threshold range(0.1-0.9).Conclusions MODS,high APACHE Ⅱ score,low oxygenation index,low neutrophil count,and low fibrinogen concentration are independent risk factors for 28-day mortality in SA-AKI patients.The developed nomogram risk prediction model may provide important guidance for predicting 28-day mortality in SA-AKI patients.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)％,(61.91±4.40)％and(118.07±10.01)％;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.

Objective To develop a two-dimensional liquid chromatographic method for rifapentine blood concentration determination.Methods The blood concentration of rifapentine was determined by a novel two-dimensional liquid chromatography(2D-LC)with a one-dimensional column:Aston SC2T(3.5 mm ×50.0 mm,5 μm);a two-dimensional column:Aston SCB(4.6 mm ×250.0 mm,5 μm);the temperature of the column was 40 ℃;the flow rate was 1.0 mL·min-1;the detection wavelength was 335 nm;the injection volume was 300 μL.The specificity,standard curve and lower limit of quantification,precision and recovery,and stability of the method were investigated.The method was used to determine the blood concentration of rifapentine in tuberculosis patients.Results Rifapentine showed good linearity within 0.33-18.62 μg·mL-1 with the standard curve equation of y=2.68 x 105x-5 850.36(r=0.997),the recoveries were 99.81％-105.08％,and the intra-and inter-day precision were ≤4.84％.The results of rifapentine blood concentration measurements in tuberculosis patients were in the range of 0.10-54.70μg·mL-1,and 64.74％were within the therapeutic window concentration range(8-30 μg·mL-1).Conclusion The method is easy to operate,has high sensitivity,low detection limit and high specificity,and is suitable for clinical blood concentration determination.Individual differences in the administration of rifapentine in tuberculosis patients are large,and blood concentration monitoring is required for individualized treatment.

Background::Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear.Methods::The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference.Results::A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories.Conclusions::The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.