Aim To investigate the effect of U50488H(a selective κ-opioid receptor agonist)and isoproterenol(ISO,a β-adrenergic receptor agonist)on ventricular arrhythmias and Cx43 during myocardial ischemia and reperfusion in rats.Methods 60 rats were randomly divided into five groups,ie,normal control group,I/R group,ISO+I/R group,U50488H+ISO+I/R group,Nor-BNI+U50488H+ISO+I/R group.The incidence of ventricular arrhythmias and arrhythmia score were determined. The expression of Cx43mRNA was tested by RT-PCR.The expression of Cx43 protein in myocardial cell was tested by an immunohistochemical approach with a quantitative imaging system.Results ① Compared with the I/R group,arrhythmia score was increased with administration of ISO(P<0.05).U50488H intravenously injected before ISO significantly decreased the arrhythmia score(P<0.05).② Compared with the normal control group,the expression of Cx43 mRNA was decreased in the I/R group(P<0.05).With administration of ISO,the amount of Cx43 mRNA was not significantly increased.③ Compared with normal control group,total and phosphorylated Cx43 proteins were significantly decreased in the I/R group(P<0.05),and the phosphorylated Cx43 was also decreased with administration of ISO.Compared with ISO+I/R group,phosphorylated Cx43 was increased with administration of U50488H (P<0.05).Conclusion κ-opioid receptor agonist U50488 H antagonizes the arrhythmias through the regulation of Cx43 during myocardial ischemia and reperfusion via inhibiting β-adrenergic receptor pathway.

Objective To investigate the relationship between cytochrome P 450 (CYP)2C19*2 / *3 gene polymorphism and antiplatelet effect of clopidogre in patients with ischemic stroke. Methods A total of 102 consecutive patients with acute ischemic stroke admitted to the Suzhou Integrated Traditional and Western Medicine Hospital from November 2012 to February 2014 were enrolled. The patients allergic to clopidogre,intolerant to clopidogrel,and recently using clopidogre were excluded. The patients were divided into a strong metabolic type group (n = 39),a moderate metabolic type group (n = 54),and a week metabolic type group (n = 9)according to the conditions of CYP2C19*2 and *3 locus mutation. The genotypes of the CYP2C19*2 and *3 were detected by the direct gene sequencing method in all patients. The maximum aggregation ratio (MAR)of platelet and platelet reactivity index (PRI)were detected beforeand 7 d after taking clopidogre 75 mg. Results (1)According to the CYP2C19*2 and CYP2C19*3, the genotyping was performed. The strong metabolic type group included *1 / *1 type 39 cases (38. 2%);the moderate metabolic type group included *l / *2 type 44 cases (43. 1%);*l / *3 54 cases, 10 (9. 8%);and the week metabolic type group included *2 / * type 27 cases (6. 9%);*2 / *3 type 2 cases (2. 0%). No *3 / *3 type was detected. (2)There were no significant differences in MAR before taking clopidogrel among the 3 groups (all P > 0. 05). After taking clopidogrel for 7 days,MAR and PRI were detected from strong to weak,followed by the week metabolic type group (49 ± 12% vs. 64 ± 15%), the moderate metabolic type group (42 ± 13% vs. 56 ± 14%),and the strong metabolic type group (33 ± 10% vs. 43 ± 12%);MAR was detected from high to low,followed by the strong metabolic type group (20 ± 12%),the moderate metabolic type group (10 ± 8%),and the week metabolic type group (7 ± 3%). Comparing the moderate metabolic type group and the week metabolic type group with the strong metabolic type group,there were significant differences between MAR,the decreased MAR and PRI (all P < 0. 01). Comparing the week metabolic type group with the moderate metabolic type group,there were no significant differences between MAR,the decreased MAR and PRI (all P > 0. 05). Conclusion The CYP2C19*2 and *3 gene polymorphisms may affect MAR and PRI after taking clopidogrel in patients with ischemic stroke.

BACKGROUND:Stem cel is a kind of pluripotent cels with self-replication ability, which can differentiate into various cels under certain conditions. Furthermore, stem cels are rich in a variety of growth factors, which can induce the generation of vessels and nerves, and improve the blood supply of lower limbs, thereby achieving the treatment and preventions of lower limb ischemia OBJECTIVE:To summarize and compare the recent achievements in the theory and therapeutic efficacy of stem cels from different sources in the treatment of diabetic foot. METHODS:The first and second authors retrieved PubMed, Sciencedirect and Medline databases for relevant articles published from January 2000 to January 2015. The key words were “diabetic foot, pathogenesis, stem cel therapy” in English. Initialy, 186 articles were retrieved, and finaly 44 articles were included in result analysis. RESULTS AND CONCLUSION:Stem cels can be a new choice for the treatment of diabetic foot. After stem cel therapy, corresponding symptoms have been aleviated, including the generation of new blood vessels and the reshaping of the colateral vessels, the improvement of motor nerve conduction velocity and nerve reflex, the improvement of the sense of skin pain and temperature, and pain relief. It is stil unclear whether alogeneic stem cels are safe or not, but autologous stem cels, especialy bone marrow mesenchymal stem cels, can be better able to repair damaged vessels and nerves and restore the microcirculation of blood supply. Currently, we need to do more basic and clinical researches to solve the folowing problems: to confirm the effectiveness and safety of stem cel therapy for diabetic foot; to identify whether there is a difference in the differentiation and secretory activity between stem cels in diabetic patients and ordinary people; to give ful play to the treatment of diabetic foot.

Objective To investigate the effects of subclinical hypothyroidism (SCH) on blood glucose and metabolic parameters in type 2 diabetes (T2DM) . Methods A total of 973 T2DM patients were recruited, and the clinical data, biochemical and thyroid function parameters were measured. One hundred and forty eight T2DM patients were diagnosed as SCH (SCH group) and 152 euthyroid patients were selected as control group (NSCH group) . Results (1) The prevalence of SCH in type 2 diabetes was 15.3% (148/973) . (2) Compared with the NSCH group, the prevalence of overweight/obesity was significantly higher in SCH group (54.1%vs 35.5%,<0.01) as well as hypertension (64.9%vs 52%, <0.05) . There was no significant difference in HbA1c control and prevalence of dyslipidemia and hyperuricemia between two groups. Conclusion SCH may have some adverse effects on blood pressure and BMI in T2DM.

Immunosuppressants, which are commonly used for liver transplantation, mainly included calcineurin inhibitors, such as ciclosporin (CsA) and tacrolimus (FK506); glucocorticoid drugs, such as prednisone and prednisolone; cytotoxic drugs, such as azathioprine, mycophenolate mofetil and cyclophosphamide; mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus; antibody drugs, such as polyclonal or monoclonal antibodies and interleukin (IL)-2 receptor antibodies, etc. Although many categories of immunosuppressants are available, FK506 is the most commonly adopted in liver transplant recipients. However, FK506 can provoke significant adverse effects in the late stage of liver transplantation, especially severe infection and nephrotoxicity. Consequently, it is an urgent task and research hot spot to develop new immunosuppressants with strong immune tolerance and mild adverse effects in clinical practice. In this article, the research progress on immunosuppressants and the research and development status of new immunosuppressants for liver transplantation were reviewed.

End-stage liver disease (ESLD) is a serious threat to human health, and liver transplantation is the only effective treatment. However, most of the patients died in the process of waiting for transplantation due to the shortage of liver source. With the rapid development of biological tissue enginee-ring technology, researchers have established the strategy of 'decellularized and recellularized technology’, which has deve-loped into the first choice for construction of important organs such as the liver and opened up new ideas for the treatment of ESLD. At present, scientists are working on the optimization of this technology, in order to construction a functional 'new liver’ for transplantation. The authors review the feasibility and challenges of the application of this technology and its optimization stra-tegy in the field of regenerative surgery.

Objective:To investigate the different types of renal artery involvement in Stanford type B aortic dissection (TBAD) and the comparison of clinical effecacy after thoracic endovascular aortic repair (TEVAR).Methods:This is a retrospective cohort study included 330 patients with TBAD and renal artery involvement treated with TEVAR from June 2002 to September 2021 in General Hospital of Northern Theater Command of the PLA. According to aortic CTA image, unilateral renal artery involvement conditions were divided into 5 types: the true lumen type (renal artery opening completely from the true lumen), false lumen type (renal artery opening completely from the false lumen), double lumen type (renal artery opening from the true and false double lumen), compression type (renal artery opening connected with the true lumen, but the renal artery opening was extremely squeezed by the inner membrane), open type (renal artery opening with intimal tear). There were seven types of bilateral renal artery involvement: true-true type (true lumen-true lumen type), true and false type (true lumen-false lumen type), true-double type (true lumen-double lumen type), true-opening type (true lumen-opening type), false-false type (false lumen-false lumen type), false-compression type (false lumen-compression type), double-double type (double lumen-double lumen type). The primary observation index of this study was the comparison of postoperative renal function and the incidence of clinical adverse events of different types of renal artery involvement. One-way ANOVA test, Kruskal-Wallis H test and paired sample rank sum test were used to compare postoperative renal function between different types of bilateral renal artery involvement. The Chi-square test or Fisher′s exact probability test were used to compare the near and long term adverse events between different types of bilateral renal artery involvement. Kaplan-Meier method was used to compare the all-cause mortality of patients with severe renal functional injury and non-severe renal functional injury before surgery. Results:The average age of the patients included in this study was (53±11) years, including 276 males (83.6%) and 54 females (16.4%). There were statistical difference in the level of serum creatinine (preoperative: H=18.686, P=0.005, postoperative: H=18.101, P=0.006) and cystatin C (preoperative: H=17.566, P=0.007, postoperative: H=10.433, P=0.016), pre-and post-operative, between the seven groups of TBAD patients with different renal artery involvement types ( P<0.05), and the false-false type group shown the worst kidney function. However, no statistically significant differences were shown when comparing their pre- and post-operative change values ( P>0.05). The 30-day follow-up result showed that there were statistically significant differences in the incidence of postoperative acute kidney injury ( χ2=15.623, P=0.007), aorta-related adverse events ( χ2=15.523, P=0.010), and intraoperative endoleak ( χ2=17.935, P=0.004) among the seven groups, and the false-false group was the highest (2/9, 5/9 and 5/9, respectively). In terms of long-term follow-up results, there were statistically significant differences in all-cause death ( χ2=14.772, P=0.011) and non-aortic death ( χ2=15.589, P=0.008) among the seven groups. Kaplan-Meier survival analysis showed that patients with worse pre-operative renal function showed higher long-term all cause death (17.7% vs. 4.8%, P=0.009). Conclusions:For TBAD patients with renal artery involvement, there were differences in renal function among different types, and TEVAR showed no significant effect on renal function in TBAD patients. The long-term all cause death was higher in patients with worse renal function pre-operative.

Objective To evaluate the safety and efficacy of transcatheter arterial embolization (TAE) in the management of refractory hematuria of prostatic origin (RHPO). Methods This retrospective study from 6 hospitals in china consisted of 31 patients (mean age 75.0±7.5 years, range 58 to 84 years) who underent transcatheter arterial embolization (TAE) for RHPO between February 2011 and January 2017. Patients with RHPO who had complete imaging and clinical data were enrolled. Patients with incomplete clinical data, inability to assess hemostasis, and contraindications to TAE were excluded. The cause of RHPO was benign prostatic hyperplasia (BPH) in nine patients, prostate cancer in twelve, transurethral resection of prostate in four, open prostatectomy in two and prostatic sarcoma in four. Superselective arterial embolization, non-superselective arterial embolization or intra-arterial infusion chemotherapy was performed according to the etiology and angiography. Angiographic findings, technical success rate, clinical success rate, complications were recorded. Results Of the 31 patients, 6 patients (19.4％) were with active bleeding, 4 (12.9％) with aneurysm and 27 (87.1％) with abnormal neovascularization on the angiogram. The 31 patients underwent a totle of 37 TAE, the technical success rate was 100.0％(37/37) and the recent hemostasis success rate was 90.3％(28/31). The incidence of mild complications was 38.7％(13/31), there was no serious complication associated with TAE. Conclusion TAE is a safe and effective method for the treatment of refractory hematuria of prostatic origin.

Objective:To investigate the clinical effect of turbocharged large free anterolateral thigh flaps (ALTF) by anastomosis with a superior perforator of the flap in reconstruction of large soft tissue defects of limbs.Methods:From June 2017 to June 2021, 6 patients with large soft tissue defects of limbs with exposed joints and tendons were treated in the Department of Hand and Foot Surgery of the Affiliated Hospital of Qingdao University with turbocharged large free ALTFs. The pressurised blood supply of ALTF was achieved by anastomosing a superior perforating branch carried in the flap. Such large and turbocharged ALTFs were used to repair large soft tissue defects with exposed joints and tendons in limbs. Of the 6 patients, there were 4 males and 2 females, and aged 32-60(46.0±8.1) years old. Cause of injury: 5 by traffic accident and 1 by machine crush. Four patients had soft tissue defects in lower limbs: 2 with open tibia and fibula fractures, 1 had patellar defect and fibula fracture, and 1 associated with fibula fracture. The other 2 patients had soft tissue defect in upper limbs with bone and tendon exposed but without fracture. The sizes of wound were 25.0 cm×12.0 cm-35.0 cm×19.0 cm. In the primary surgery, Vacuum sealing drainage (VSD) was applied. In the second stage, free ALTFs were used to cover the wound. The area of flap incision was increased by anastomosing the superior perforators and as the consequence, the size of flaps was achieved to 26.0 cm×13.0 cm-36.0 cm×15.0 cm. Donor site of 6 cases were reduced by direct suture, and the remaining wound was covered by free skin graft. Postoperative follow-ups were conducted at outpatient clinic reviews at 1, 2, 3 and 6 months after surgery, and followed by telephone or WeChat interviews. The results of the operation were evaluated according to the appearance, texture and sensory recovery of the flap.Results:All 6 flaps survived and the patients completed the postoperative follow-up that lasted for 6-24 (16.7±5.0) months. No necrosis of flap occurred after surgery. The appearance and texture of the flaps were satisfactory without wear and tear. Sensation recover was evaluated by the standered of British Medical Research Council (BMRC), 4 patients recovered to S 3 and 2 patients to S 2. The Mayo score of the elbow joint was good in 2 patient with upper extremity injuries. Of the other 4 patients with lower limb injuries, the knee function evalued by Hospital for Special Surgery(HSS) score were excellent in 3 patients and good in 1 patient, and the American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hind foot function score was excellent in 2 patients and good in 2 patients. There was no infection or function loss at all donor sites. Conclusion:The perforator of an ALTF is relatively constant, and the flap can partially restore sensation. The superior perforator is reliable and the incision area of the flap can be enlarged by anastomosing the superior perforator vessels. It is a better way to reconstruct a large soft tissue defects in limbs.

Objective:To investigate the clinical effect of free posterior tibial artery perforator flap in repair of forefoot soft tissue defect.Methods:From January 2017 to January 2021, a retrospective study was conducted on 13 patients with forefoot soft tissue defect, metatarsal head exposed, and forefoot transverse arch integrity, including 9 males and 4 females. The age was (40.0±13.0) years old. Cause of injury: 8 cases of traffic accident injury, 5 cases of heavy object smashing injury. Seven cases had forefoot skin defect and toe damage, and 6 cases had forefoot skin avulsion injury, open toe fracture with tendon, blood vessel and nerve injury. The wound area was 4.5 cm×3.0 cm-8.0 cm×6.0 cm. VSD treatment was performed in the first stage, and free posterior tibial artery perforator flap was used for the second stage. The flap area was 5.5 cm×4.0 cm-9.0 cm×7.0 cm. Outpatient reviews scheduled at 1, 2, 3, and 6 months after surgery, through outpatient clinic, telephone or WeChat. The flaps were evaluated according to appearance, texture, sensory recovery, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot function scoring system.Results:All 13 flaps survived. The follow-up lasted for 6 to 24 months. The feet were in good shape, walking with weight beries, and the flaps had satisfactory appearance without wear and tear. Five cases were S 3, 6 were S 2, and 2 were S 1. According to AOFAS ankle-hindfoot function score, 4 had excellent scores, 7 were in good, and 2 in fair. Conclusion:The free posterior tibial artery perforator flap has relatively constant perforators, and the pedicle of the middle and upper perforators is longer, and the flap can build part of the sensation. Posterior artery perforator flap is a good flat for repairing the soft tissue defects of the metatarsal head of the forefoot.