OBJECTIVE To investigate the effect and mechanism of self-assembled nanoparticles from Shaoyao gancao decoction （SGD-SAN） on the intestinal absorption behavior of its main active components. METHODS SGD-SAN was prepared and characterized. Using an in-situ single-pass intestinal perfusion model in rats， the absorption characteristics of five active components （albiflorin， paeoniflorin， liquiritin apioside， liquiritin， glycyrrhizic acid） from SGD-SAN in the jejunum and ileum were studied， with the absorption rate constant （ K a ） and apparent permeability coefficient （ P eff ） as indicators， and compared with free drugs. In the intestinal segment with optimal absorption， the effects of drug concentration and efflux transporter inhibitors （P-glycoprotein inhibitor verapamil， multidrug resistance-associated protein 2 inhibitor indomethacin， breast cancer resistance protein inhibitor reserpine） on the intestinal absorption characteristics of these components were examined. RESULTS The obtained SGD-SAN exhibited a spherical shape with uniform sizes， an average particle diameter of （155.57±2.65） nm， a polydispersity index of 0.34±0.03， and a Zeta potential of （－9.30±1.12） mV. The average total content of five active components， including albiflorin， was 12.26%， and remained unaffected by enzymatic degradation and intestinal physical absorption. Compared with the free drug group， the five active components in the SGD-SAN group exhibited higher absorption rates in the ileal segment， with significantly elevated K a and P eff values （except for the P eff value of glycyrrhizic acid in the ileal segment） （ P ＜0.05 or P ＜0.01）. Their absorption demonstrated a concentration-dependent trend. In the free drug groups， the absorption of each component was regulated by corresponding inhibitors （ P ＜0.05 or P ＜0.01）； whereas in the SGD-SAN groups， except for albiflorin and paeoniflorin， the absorption of the remaining components was not affected by the inhibitors （ P ＞0.05）. CONCLUSIONS SGD-SAN significantly enhances the intestinal absorption efficiency of active components. The above absorption-enhancing effect may be related to the avoidance of efflux transporter influence and the presence of a mixed absorption mode.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death(DBD)donors complicated with acute kidney injury(AKI).Methods Clinical data of 216 DBD donors were retrospectively analyzed,and they were divided into the AKI group(n=69)and control group(n=147)according to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines.Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups.One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group.Postoperative recovery of renal function and clinical outcomes of the recipients were recorded.The risk factors of delayed graft function(DGF)were identified.Results The highest serum creatinine(Scr)level,Scr level before procurement,the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group.The application duration of vasopressors in the AKI group was longer than that in the control group.In the AKI group,the amount of fluid resuscitation within 48 h was higher,the HCO3-level at admission was lower,and the incidence of diabetes insipidus and hypotension was higher than those in the control group.The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts(all P＜0.05).Compared with the control group,the incidence of DGF and acute rejection was higher,the proportion of continuous renal replacement therapy was higher,the Scr level within postoperative 90 d was higher,and the urine amount within postoperative 3 d was less than those of recipients in the AKI group.Compared with KDIGO stage 1 recipients,KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3,4,5 and 15 d,and less urine amount at postoperative 2 d(all P＜0.05).Univariate analysis showed that donor age,the highest Scr level,the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation.Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation(all P＜0.05).Conclusions For the application of DBD donors complicated with AKI,active organ maintenance should be performed to alleviate AKI.It exerts no effect upon graft function and survival rate at postoperative 6 months,which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys.

OBJECTIVE: To assess the value of mapping allele with resolved carrier status (MaReCs) technology for the determination of balanced translocation carrier status for embryos. METHODS: Blastocysts produced by 25 reciprocal translocation carriers and 15 Robertsonian translocation carriers were detected by MaReCs. After genetic counseling, transplantable blastocysts were selected. Amniocentesis was performed to check fetal chromosomes at 16 to 20 gestational weeks, and the consistency of amniocentesis and MaReCs was determined. RESULTS: No significant difference was found in the normal rate for chromosome copy number variations (CNVs) in blastocysts between reciprocal translocation carriers and Robertsonian translocation carriers (28.6% vs. 32.0%, P> 0.05). For 12 (48%) reciprocal translocation carriers and 8 (32%) Robertsonian translocation carriers, the status of translocation carrier of embryos was successfully determined. The results of amniocentesis were consistent with that of MaReCs in all 11 pregnancies. CONCLUSION MaReCs is a reliable method to distinguish the translocation carrier status of embryos of balanced translocation carriers. It can help a certain proportion of balanced translocation carriers to select completely normal embryos while reduce transfer of embryo carrying a balanced translocation.

A 54-year-old man was admitted to respiratory department with chief complaints of recurrent cough and dyspnea. Chest imaging showed multiple patchy shadows and interstitial changes. Evidence of infectious diseases was not definite, and antibiotic treatments were not effective. In the meantime, myelodysplasia syndrome was diagnosed with pancytopenia. The pathologic findings of transbronchoscopic lung biopsyshowed chronic inflammatory interstitial changes, suggesting a clinical diagnosis of organizing pneumonia. After glucocorticoids treatment, his condition aggravated. The second percutaneous lung biopsy showed the infiltration of a large number of neutrophils. Therefore, the final diagnosis of myelodysplasia syndrome with Sweet syndrome was made. Then glucocorticoids and supportive treatment were given This case may improve physicians' understanding of myelodysplasia syndrome complicated with Sweet syndrome.

Objective: To investigate the risk factors of postoperative acute kidney injury (AKI) in patients aged between 40 and 50 years old undergoing cardiac valvular surgery and the impact on outcome. Methods: The clinical data of 286 patients aged between 40 and 50 years old undergoing cardiac valve surgery in Guangdong Provincial People′s Hospital from January 2012 to December 2016 were analyzed retrospectively. Preoperative coronary angiography was performed in all patients. All patients enrolled were divided into AKI group and non-AKI group according to the existence or not of postoperative AKI. Patients with AKI were further divided into AKI stage 1, stage 2, and stage 3 groups according to KDIGO guideline. Demographic characteristics, preoperative clinical data including serum creatinine, estimated glomerular filtration rate, hemoglobin, uric acid, urinary protein, presence or absence of chronic kidney disease, left ventricular ejection fraction, pulmonary artery pressure, New York Heart Association (NYHA) functional classification, preoperative co-morbidity (hypertension, diabetes, anemia, cerebrovascular disease, peripheral artery disease), preoperative medication(vasoactive drugs, diuretic, renin-angiotensin system inhibitor (RASI), surgical data (contrast dosage in coronary angiography, type of cardiac valve surgery) were recorded and analyzed in this retrospective study. The risk factors for postoperative AKI and its impact on clinical outcomes (mortality, hospitalization expenses and Intensive Care Unit stay duration) were evaluated. Logistic regression analysis was used to determine the risk factors for postoperative AKI and the adjusted variables with P<0.2 were selected for the multivariate logistic regression analysis to define the independent determinants for AKI. Results: AKI was defined in 106 out of 286 enrolled patients, including 96 patients with AKI stage 1, 10 patients with AKI stage 2 and no patients with AKI stage 3. The proportion of coexisting cerebrovascular diseases was higher in AKI group than in non-AKI group (9(8.49%) and 5(2.78%), χ²=4.677, P=0.031), while there was no difference among other baseline data between the two groups. Multivariate logistic regression analysis showed that preoperative complications of cerebral vascular disease was an independent risk factor of postoperative AKI (OR=3.578, 95%CI 1.139-11.242, P=0.029). Five out of 106 AKI patients died during hospitalization while there was only 1 patient died among 180 patients without AKI. Patients with AKI after cardiac valve operation experienced higher mortality than patients without AKI (χ²=5.625, P=0.028). Further analysis showed that there was no difference in hospitalization mortality between patients with AKI stage 2 and stage (χ²=0.686, P=0.408) while the hospitalization mortality in patients with AKI stage 2 was higher than those without AKI (χ²=8.113, P=0.004). The hospitalization expenses in patients with AKI were 10.38(8.59,12.54) ×10⁴ RMB, significantly higher than that in patients without AKI (9.72(8.03,11.93) ×10⁴ RMB)(P=0.043). There was no difference in hospitalization expenses between patients with AKI stage 1 and without AKI (P=0.635). The hospitalization expenses in patients with AKI stage 2 was higher than those without AKI (P=0.023). Intensive Care Unit stay duration in patients with AKI was 3(1,4) days, significantly higher than those without AKI (P=0.044). There was no difference in Intensive Care Unit stay duration in patients with AKI stage 1 and without AKI (P=0.978), while Intensive Care Unit stay duration in patients with AKI stage 2 was significantly longer than those without AKI (P=0.006). Conclusions Preoperative complications of cerebral vascular disease is an independent risk factor of postoperative AKI. Non-senile patients with AKI after cardiac valvular surgery is associated with a higher proportion of mortality, hospitalization expenses and Intensive Care Unit stay duration as compared patients without postoperative AKI.

Objective To investigate the effects of PPAR-gamma expression on reperfusion arrhythmias in different precon ditioning myocardial ischemia/reperfusion(I/R) animal model.Methods Thirty-two SD rats were randomly divided into 4 groups(n =8):rosiglitazone+ I/R group (ROS group),GW9662 + I/R group(GW group),I/R group and sham group (Sham group).The I/ R animal model was constructed by ligation of the left anterior descending coronary artery,with ischemia for 30 min and reperfusion for 120 min.The dynamic limb Ⅱ lead electrocardiogram monitoring was performed;PPAR-gamma mRNA was detected by fluorescent quantitative PCR and the change of PPAR-gamma protein expression was detected by Western blot.Results The increasing range of QRS wave width detected before operation,at 30 min of ischemia,at 1,2 h of reperfusion from large to small were in turn the ROS group,I/R group,GW group and Sham group;the reperfusion arrhythmia score in the ROS group was significantly higher than that in the other groups(P＜0.05),while the GW group was relatively reduced.The expression level of PPAR-gamma mRNA in the ROS group detected by fluorescent quantitative PCR was significantly up-regulated(P＜0.05),while which in the GW group was down-regulated compared with the I/R group and ROS group(P＜0.05).The expression of PPAR-gamma protein was similar to that of PPAR-gamma mRNA.Conclusion Up-regulation of myocardial PPAR-gamma expression may increase the occurrence of reperfusion arrhythmias in myocardial I/R animal model.

Objective To discuss the safety and efficacy of using ExoSealTM vascular closure device to obtain rapid hemostasis of puncture site in interventional procedure via retrograde femoral artery access.Methods The clinical data of 124 patients,who were admitted to authors' hospital during the period from March 2016 to April 2016 to receive interventional procedure via retrograde femoral artery access,were retrospectively analyzed.During the performance of intervention,ExoSealTM vascular closure device (ExoSealTM group,n=52) or manual compression (MC group,n=72) was employed to make femoral artery puncture point hemostasis.The time spent for hemostasis,the manual compression time,the limb immobilization time,the amount of blood loss during compression process,and the procedure-related complications were recorded and the results were compared between the two groups.Results Technical success rate in ExoSealTM group was 98.1％(51/52).In ExoSealTM group and MC group,the time spent for hemostasis was (0.28±0.08) min and (5.83±1.46) min respectively,the manual compression time was (2.65 ±0.57) min and (7.70± 1.88) min respectively,the limb immobilization time was (2.72±0.43) h and (6.15±0.69) h respectively;all the differences between the two groups were statistically significant (P＜0.01).In ExoSealTM group subcutaneous hemotoma occurred in one patient,while in MC group subcutaneous hemotoma occurred in 3 patients and pseudoaneurysm in one patient;the complication rates were 1.92％ (1/52) and 5.56％ (4/72) respectively,but the difference was not statistically significant (P＞0.05).In MC group the amount of blood loss during compression process was (1.11±0.86) ml,which was remarkably less than (7.83±2.08) ml in ExoSealTM group,the difference between the two groups was statistically significant (P＜0.01).Conclusion For hemostasis of puncture site in interventional management via retrograde femoral artery access,the use of ExoSealTM vascular closure device is safe and effective.