PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

AIM To study the effects of total flavonoids of Dracocephalum Moldavica L.(TFDM)on reducing the inflammatory response of RAW264.7 macrophages induced by ox-LDL via the nuclear factor κB(NF-κB)/NOD-like receptor 3(NLRP3)signaling pathway.METHODS The RAW264.7 macrophages cultured in vitro were divided into the normal group,the model group(50 μg/mL ox-LDL),the TFDM group(100 μg/mL TFDM+50 μg/mL ox-LDL),the NF-κB inhibitor group(10 μmol/L Bay11-7821+50 μg/mL ox-LDL)and the TFDM+NF-κB inhibitor group(100 μg/mL TFDM+10 μmol/L Bay11-7821+50 μg/mL ox-LDL).The cells had their viability assessed by CCK-8 method;their ROS expression detected by the ROS kit;their mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β detected by RT-qPCR;their protein expressions of NF-κB p65,IκBα,NLRP3,pro-Caspase-1,Caspase-1,IL-18 and IL-1β by Western blot;their protein expressions of NF-κB p65 and NLRP3 detected using immunofluorescence method.RESULTS Compared with the normal group,the model group showed increased ROS expression(P＜0.01);increased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01);decreased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.01);increased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.01);and increased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).Compared with the model group,the groups intervened with either TFDM or TFDM+inhibitor displayed decreased ROS expression(P＜0.01);the groups administrated with TFDM or NF-κB inhibitor,or TFDM+inhibitor showed decreased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01),increased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.05,P＜0.01),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1β and IL-18(P＜0.05,P＜0.01),and decreased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).There existed no significant group difference between the TFDM group and the NF-κB inhibitor group(P＞0.05).The TFDM+inhibitor group demonstrated decreased mRNA expressions of IL-1βand IL-18(P＜0.05),increased IκBα protein expression(P＜0.05),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.05),and decreased fluorescence intensity of NLRP3 protein(P＜0.05).CONCLUSION TFDM can inhibit the ox-LDL-induced inflammatory response of RAW264.7 macrophages,and the mechansism may be associated with the reduced ROS expression and inflammatory factors due to the inhibited activation of the NF-κB/NLRP3 signaling pathway.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

AIM To study the effects of total flavonoids of Dracocephalum Moldavica L.(TFDM)on reducing the inflammatory response of RAW264.7 macrophages induced by ox-LDL via the nuclear factor κB(NF-κB)/NOD-like receptor 3(NLRP3)signaling pathway.METHODS The RAW264.7 macrophages cultured in vitro were divided into the normal group,the model group(50 μg/mL ox-LDL),the TFDM group(100 μg/mL TFDM+50 μg/mL ox-LDL),the NF-κB inhibitor group(10 μmol/L Bay11-7821+50 μg/mL ox-LDL)and the TFDM+NF-κB inhibitor group(100 μg/mL TFDM+10 μmol/L Bay11-7821+50 μg/mL ox-LDL).The cells had their viability assessed by CCK-8 method;their ROS expression detected by the ROS kit;their mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β detected by RT-qPCR;their protein expressions of NF-κB p65,IκBα,NLRP3,pro-Caspase-1,Caspase-1,IL-18 and IL-1β by Western blot;their protein expressions of NF-κB p65 and NLRP3 detected using immunofluorescence method.RESULTS Compared with the normal group,the model group showed increased ROS expression(P＜0.01);increased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01);decreased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.01);increased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.01);and increased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).Compared with the model group,the groups intervened with either TFDM or TFDM+inhibitor displayed decreased ROS expression(P＜0.01);the groups administrated with TFDM or NF-κB inhibitor,or TFDM+inhibitor showed decreased mRNA expressions of NF-κB p65,NLRP3,Caspase-1,IL-18 and IL-1β(P＜0.05,P＜0.01),increased protein expressions of IκBα and cytoplasmic NF-κB p65(P＜0.05,P＜0.01),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1β and IL-18(P＜0.05,P＜0.01),and decreased fluorescence intensity of NF-κB p65 and NLRP3(P＜0.01).There existed no significant group difference between the TFDM group and the NF-κB inhibitor group(P＞0.05).The TFDM+inhibitor group demonstrated decreased mRNA expressions of IL-1βand IL-18(P＜0.05),increased IκBα protein expression(P＜0.05),decreased protein expressions of nuclear NF-κB p65,NLRP3,Caspase-1,IL-1 β and IL-18(P＜0.05),and decreased fluorescence intensity of NLRP3 protein(P＜0.05).CONCLUSION TFDM can inhibit the ox-LDL-induced inflammatory response of RAW264.7 macrophages,and the mechansism may be associated with the reduced ROS expression and inflammatory factors due to the inhibited activation of the NF-κB/NLRP3 signaling pathway.

Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P＜0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P＜0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.

Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.