Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

Objective To investigate the impact of cardiomyocyte ferroptosis on acute myocardial infarction(AMI)and its relationship with the expression of long non-coding RNA(lncRNA)GAS5.Methods An AMI model was established in eighteen male SD rats(6-8 weeks old),and then the subjected rats were randomly divided into blank control group,sham operation group,and model group,6 animals in each group.In 2 weeks after surgery,echocardiography was used to evaluate heart function,and TTC staining,HE staining and TUNEL staining were employed re-spectively to observe myocardial infarct area,histopathological changes of myocardial tissues and apoptosis in cardiomyocytes.Serum Fe2+concentration was measured with an iron ion detection kit.The expression levels of lncRNA GAS5,nuclear factor erythroid-derived 2-like 2(Nrf2),and glutathione peroxidase 4(GPX4)in myocardial tissues were detected with QT-PCR.Linear corre-lation analysis was performed to investigate the relationship between the expression of lncRNA GAS5,Nrf2 and GPX4 with Fe2+concentration.Western blotting was conducted for the protein levels of ferroptosis-related proteins,glutathione peroxidase 4(GPX4),nuclear factor erythroid-derived 2-like 2(Nrf2),glucose-regulated protein 78(GRP78),and cysteinyl aspartate specific proteinase 12(Caspase-12)in myocardial tissues.Results Western blotting revealed obvious in-creases in the protein levels of ferroptosis related proteins GRP78(1.11±0.13 vs 0.51±0.08,P＜0.01)and Caspase-12(1.23±0.05 vs 0.92±0.07,P＜0.05)and a decrease in those of ferroptosis inhibitor GPX4(0.27±0.11 vs 0.68±0.10,P＜0.01)and Nrf2(0.30±0.12 vs 0.58±0.04,P＜0.05)in the model group than the sham operation group.Additionally,QT-PCR showed that the mRNA levels of GPX4 and Nrf2 were notably lower,indicating cardiomyocyte ferroptosis,while that of lncRNA GAS5 was remarkably higher in the myocardial tissues of the model group than the sham operation group(P＜0.01).What's more,the expression of lncRNA GAS5 had a positive correlation with serum Fe2+concentration(P＜0.05).Conclusion AMI is closely associated with cardiomyocyte ferroptosis.lncRNA GAS5 is involved in the regulation of ferroptosis by Nrf2/GPX4 signaling pathway,which thus mediating the occurrence of heart failure after AMI.

Objective:To analyze the effect of endovascular therapy (including balloon dilation, debulking and anti-restenosis technique) for below-the-ankle atherosclerotic lesions in chronic limb threatening ischemic patients.Methods:A retrospective analysis was performed on the clinical data of 465 patients (570 limbs) with below-the-ankle atherosclerosis who were consecutively admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2018 to December 2021. All patients received balloon dilatation below the ankle artery as basic treatment, including 67 patients in debulking subgroup, 82 patients in anti-restenosis subgroup and 11 patients in the triple therapy subgroup. The reocclusion rate, target lesion reintervention rate at 1, 3, 6 and 12 months after surgery were compared; The wound healing rate at 3 months, limb salvage rate at 6 and 12 months and mortality at 12 months in the Global Limb Anatomic Staging System (GLASS) grading groups P0, P1 and P2 were compared.Results:The technical success rate of this group was 76.0%(433 limbs/570 limbs). The follow-up rates of 6 and 12 months after operation were 85.4%(370 limbs/433 limbs) and 75.3%(326 limbs/433 limbs), respectively. The length of treated lesions was (3.6±1.3)cm; The reocclusion rates were 5.5%(23 limbs/420 limbs), 8.2%(33 limbs/403 limbs), 14.9%(55 limbs/370 limbs) and 23.6%(77 limbs/326 limbs) at 1, 3, 6 and 12 months after operation; The reintervention rate of target lesions in 6, 12 months was 7.6%(28 limbs/370 limbs) and 12.0%(39 limbs/326 limbs) respectively; The wound healing rate in groups P0, P1 and P2 within 3 months was 87.3%(192 limbs), 70.5%(62 limbs) and 10.5%(2 limbs) respectively ( P<0.001), the limb salvage rate in 6 months was 96.2%(200 limbs), 84.7%(127 limbs) and 33.3%(4 limbs) respectively ( P<0.001), and the limb salvage rate in 12 months was 78.7%(170 limbs), 54.5%(55 limbs) and 22.2%(2 limbs) respectively ( P<0.001). The mortality was 6.9%(32/465) 12 months after operation. Conclusions:Endovascular therapy below-the-ankle is feasible and has high technical success rate. The constitute integrity of pedal-plantar loop in limb- threatening phase is related to 3-month wound healing rate and limb salvage rate.

Objective:To investigate the clinical effect and short-term and long-term effect of total hip replacement (THA) and hemiarthroplasty of hip (HA) in elderly patients with femoral neck fracture (FNF).Methods:59 elderly patients with FNF in South District of Guang′anmen Hospital, Chinese Academy of Traditional Chinese Medicine from March 2017 to January 2019 were retrospectively analyzed. The observation group ( n=29) was treated with THA; The control group ( n=30) was treated with HA. The operation related indexes, short-term and long-term clinical effect (average follow-up of 24.1 months), hip function improvement, pain and complications were compared between the two groups. Short term and long-term clinical effects: the short-term and long-term clinical effects of the two groups were observed by the Harris Hip Score (HHS) of the first month, the third month, the sixth month, the ninth month and the first year after operation. Results:Both THA and HA were effective on elderly FNF, but the effective rate of THA (96.6%) was significantly higher than that of HA (90.0%), with statistically significant difference ( P<0.05); in terms of operation related indicators, compared with the control group, the observation group had longer operation time [ (104.46±3.24)min vs (84.34±3.64)min], more amount of bleeding [(296.64±15.16)ml vs (281.44±12.16)ml], lower postoperative drainage volume [(101.24±4.15)ml vs (74.56±3.24)ml], while the functional recovery of the observation group was better than the control group by HHS ( P<0.05); the postoperative complications and HHS score of observation group were significantly lower than the control group ( P<0.05). Conclusions:THA has the advantages of low complication, fast functional recovery and better effect. The clinical decision should be based on the patient′s physical condition. THA should be used for elderly patients with good basic condition, good surgical tolerance and more daily activities. HA should be used for elderly patients with poor basic condition, low surgical tolerance and less daily activities.

Objective:To investigate the effects of of anti tumor necrosis factor-α (TNF-α) in adjuvant treatment of strangulated intestinal obstruction combined with ischemic intestinal necrosis.Methods:From February 2011 to August 2016 in Huadu District People′s Hospital Affiliated with Southern Medical University, 122 patients with strangulated intestinal obstruction combined with ischemic intestinal necrosis were selected and were equally divided into the experimental group and control group with 61 cases in each group according to the random draw envelope principle. Conventional surgical resection and anastomosis was used in control group, the postoperative anti TNF-α therapy was given for 2 weeks based on the treatment in control group.Results:All patients completed surgery and there were no serious complications during operation.The postoperative anal exhaust time and symptom remission time in experimental group were significantly lower than those in control group: (2.14 ± 0.41) d vs. (6.24 ± 1.28) d and (3.54 ± 0.77) d vs. (6.99 ± 0.91) d ( P<0.05). The incidence of postoperative 14 d complications such as anastomotic leakage, wound infection, anastomotic stenosis and pulmonary infection in the experimental group was 4.9%(3/61), and that of the control group was 18%(11/61), and the incidence of postoperative complications in the experimental group was significantly lower than that in the control group ( P<0.05). The postoperative 1d and 7 d serum TNF-α content in the experimental group was significantly lower than that in the control group ( P<0.05). The postoperative 14 d anal function in the experimental group was significantly better than that in the control group ( P<0.05). MRASP and MSP of postoperative 14 d in experimental group were all significantly higher than those in the control group: (80.24 ± 11.39) mmHg (1 mmHg=0.133 kPa) vs. (76.24 ± 12.11) mmHg, (231.98 ± 45.29) mmHg vs. (226.39 ± 41.87) mmHg ( P<0.05). Conclusions:The anti TNF-α in adjuvant treatment of strangulated intestinal obstruction combined with ischemic intestinal necrosis can promote the recovery of clinical symptoms and inhibit the release of TNF-α. It also can reduce the incidence of postoperative complications and improve gastrointestinal motility of patients.

Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstn;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1β, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstn;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α(TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100μl PBS, and then 100μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200μl PBS, 100μl of which was injected into the tail vein of DSU rats (n=15), and other 100μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-αwere detected by radioimmunoassay method, and the expression of TNF-αand caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-αin the PBS group [(35.9±3.7)μg/L] were significantly higher than that of the control group [(11.4±4.9)μg/L] and the UCMSCs group [(14.7±6.6)μg/L] (all P<0.05). The levels of mRNA and protein expression of TNF-αand caspase-3 in the UCMSCs group were significantly lower than those of the PBS group (all P<0.05), and have no significant differences with respect to those of the control group (all P>0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-αand caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect.

Objective To evaluate the experience and early results of radiofrequency ablation (RFA) therapy for varicose veins.Methods In this study 380 extremities of 356 patients undergoing RFA therapy with RFA catheter for varicose veins from Nov 2015 to Sep 2017 in Beijing Tsinghua Changgung Hospital were retrospectively reviewed.Each patient was scheduled to follow up at 1,6 and 12 months respectively.Results Technical success were achieved in all cases.Obliteration rate was 99.0％ in 1 month,97.9％ in 6 months and 97.1％ in 12 months after the RFA therapy.Conclusions RFA therapy for varicose veins is safe and effective and achieves good early result.Intraoperative ultrasound examination and endovascular technique is important for a successful RFA procedure.

Penicillin expandase, also known as deacetoxycephalosporin C synthase (DAOCS), is an essential enzyme involved in cephalosporin C biosynthesis. To evaluate the catalytic behaviors of penicillin expandase under high penicillin G concentration and to identify mutants suitable for industrial applications, the specific activities of wild-type DAOCS and several mutants with increased activities toward penicillin G were determined by HPLC under high penicillin G concentrations. Their specific activity profiles were compared with theoretical predictions by different catalytic dynamics models. We evaluated the specific activities of wild-type DAOCS and previous reported high-activity mutants H4, H5, H6 and H7 at concentrations ranging from 5.6 to 500 mmol/L penicillin G. The specific activities of wild-type DAOCS and mutant H4 increased as penicillin G concentration increased, but decreased when concentrations of substrate go above 200 mmol/L. Other mutants H5, H6 and H7 showed more complex behaviors under high concentration of penicillin G. Among all tested enzymes, mutant H6 showed the highest activity when concentration of penicillin G is above 100 mmol/L. Our results revealed that the substrate inhibition to wild-type DAOCS' by penicillin G is noncompetitive. Other DAOCS mutants showed more complex trends in their specific activities at high concentration of penicillin G (>100 mmol/L), indicating more complex substrate inhibition mechanism might exist. The substrate inhibition and activity of DAOCS mutants at high penicillin G concentration provide important insight to help select proper mutants for industrial application.
Catalysis ; Intramolecular Transferases ; genetics ; Mutation ; Penicillin G ; pharmacology ; Penicillin-Binding Proteins ; genetics ; Streptomyces ; enzymology ; genetics