Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective:To investigate the results of coryoint flap harvested from lower abdominal wall for covering extremely soft tissue circular defects on limbs.Methods:From March 2018 to June 2020, 15 patients who suffered from severe degloved injury were admitted into the Department of Hand Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. The injuries were characterised as extreme circular defects on limbs. The dimension of defects ranged from 25.0 cm×9.0 cm to 30.0 cm×18.0 cm. All wounds were taken through emergency debridement and managed by VSD. Using lower abdomen as a donor site, a conjoined flap was dissected when the wound surface became granulating. The perforator vessels of the flaps included vessels of deep inferior epigastric artery(DIEA), superficial inferior epigastric artery(SIEA) and superficial circumflex iliac artery(SCIA). The donor sites were primary closed. Postoperative follow-ups were conducted by the surgeons in the same surgical team at outpatient clinic.Results:Fourteen flaps survived completely without significant complications. Distal necrosis occurred in 1 flap, which healed with a skin graft in the second stage surgery. All flaps were reviewed during the postoperative follow-up that lasted for 18-24(mean 20) months. The aesthetic outcomes were achieved on the recipient site without hairy nor hyper-pigmentation. A concealed linea scare left at the donor sites without hernia and limited function. At the last follow-up, 5 patients were in excellent and 2 in good evaluated by following the Disabilities of the arm, shoulder and hand(DASH). With the Lower extremity functional scale(LEFS), 5 patients were in excellent and 3 in good.Conclusion:The simultaneous reconstruction of extremely large soft tissue circular defects on limbs with best possible salvage surgery can be achieved by a conjoined flap. A conjoined flap offers a concealed donor site, easy to design, flexible perforators design and larger size of soft tissue.

Objective:To investigate the curative effects of bi-pedicled deep inferior epigastric perforator (DIEP) flap in repairing large soft tissue defects in the lower limbs.Methods:A retrospective observational study was conducted. From February 2016 to June 2020, 16 patients with large soft tissue defects in the lower limbs caused by trauma or after tumor/scar resection were admitted to the Department of Hand Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, including 9 males and 7 females, aged 25-58 years, with the area of soft tissue defects ranging from 14.0 cm×8.0 cm to 32.0 cm×18.0 cm. Using the abdomen as the donor site, the conjoined abdominal wall flap, i.e., the bi-pedicled DIEP flap (with an area ranging from 15.0 cm×9.0 cm to 32.0 cm×20.0 cm) carrying two sets of the trunk of the deep inferior epigastric artery was designed and resected to repair the wound. The donor site wound was sutured directly. The flap survival and wound healing in the donor and recipient areas were observed after operation. The curative effect was evaluated during the follow-up. At the last follow-up, the American Knee Society score and lower extremity functional scale were used to assess the functions of knee joint and lower limb, respectively.Results:The flaps of 15 patients survived after operation; the flap of one patient had partial infection at the edge after operation but healed after debridement and dressing change. The wounds in the donor and recipient areas of 16 patients all healed well. Follow-up of 16-28 months showed that the recipient area had a good shape and pliable texture, and there was no obvious swollen appearance, hyperpigmentation, or abnormal hair growth; the donor site had linear scar only, with no complications such as abdominal hernia or hyperplastic scar; the functions of knee joint and lower limb were well reconstructed, with no recurrence of tumor. At the last follow-up, among the 4 patients with knee joint injury, 3 cases were excellent and 1 case was good in the evaluation of knee joint function; among the 12 patients with lower limb injury, 9 cases were excellent and 3 cases were good in the evaluation of lower limb function.Conclusions:The donor site of bi-pedicled DIEP flap is concealed with abundant tissue and large area for resection, with which can be used to repair large soft tissue defects in the lower limbs, achieving good short-term results of appearance and function restoration.

Talents constitute key resources for the development of healthcare sector, and studying abroad is an important and effective means for their training. Based on the analysis of the current status of China′s international talents training project of hospitals, this study summarized existing problems in such training. The authors covered such six aspects as lawful standardization of project management methods, selection of trainees by levels and by types, innovation of the process tracking management mechanisms and strengthened full-process assessment, all dimensional institutional support, consolidation of the responsibilities by individual disciplines in talent team building, and measures to cope with the impact of COVID-19. In accordance with the research results, the study analyzed the exploration and practice of the international training project under the " Elite Talents Cultivation Project" of the Affiliated Hospital of Qingdao University, and raised targeted recommendations on attention to the strategic and forward-looking planning, precise setup of training goal categories, classified evaluation of study results, and lawful management among others.

To explore differential expression of long non-coding RNA (lncRNA) in patients with coronary artery disease plus clopidogrel resistance.
 Methods: Patients underwent percutaneous coronary intervention (PCI) and treated with clopidogrel were recruited, and their clinical data and blood samples were collected. Patients were divided into a clopidogrel sensitive group and a clopidogrel resistance group according to platelet aggregation rate. lncRNA microarray and real-time RT-PCR were performed in 5 and 34 patients in each group, respectively.
 Results: lncRNA microarray showed that 11 lncRNAs in peripheral leukocytes were up-regulated and 8 lncRNAs were down-regulated in clopidogrel resistant group. Real-time PCR indicated that two lncRNAs (NONHSAT083775.2 and NONHSAT107804.2) in leukocytes were up-regulated and one lncRNA (NONHSAT133455.2) was down-regulated in the clopidogrel resistant group compared with the clopidogrel sensitive group, consistent with the results of lncRNA microarray.
 Conclusion: Clopidogrel resistance is associated with the up-regulation of lncRNA NONHSAT083775.2 and NONHSAT107804.2 and the down-regulation of NONHSAT133455.2.
Clopidogrel ; Coronary Artery Disease ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; RNA, Long Noncoding

Objective To investigate the clinical characteristics,diagnosis and treatment of primary abdominal cocoon.Methods The clinical data of 16 cases of primary abdominal cocoon were reviewed and analyzed.Results Only in 2 cases in which correct preoperative diagnosis was estabished by CT scan.The other 14 cases were diagnosed during operation.Parts or all small intestines were covered with a layer of milky white dense fibrous thin membrane,formed mass-likely adhesion,and fibrous film attached to the mesenteric roots.Extensive adhesion existed in between intestines.The operation included lysis of peritoneal adhesion plus fibrous membrane excision in 14 cases,lysis of peritoneal adhesion plus fibrous membrane excision and segmental enterectomy in 2 cases,and in 2 cases appendectomy was done.There was no anastomotic leakage or other major complications except for wound infection in 1 case.All the patients were followed up from 3 months to 7 years with a median follow-up time of 3.6 years,and no recurrent cases were found.Conclusions Surgery is the main method for the treatment of abdominal cocoon with evident clinical symptoms,and the prognosis is largely fair.

Objective To investigate early diagnosis and treatment of Paget disease of breast. Methods The clinicopathological data of 26 cases of breast Paget disease in the First Affiliated Hospital of Wenzhou Medical University from January 1995 to June 2018 was analyzed. Results The main clinical manifestation of 26 patients was eczema like papillae in 19 cases (73.1%), and associated with nipple discharge in 9 cases (34.6% ) and breast mass in 6 cases (23.1% ). The diagnosis of this disease was based on curettage cytology in 4 cases (15.4% ), biopsy in 8 cases (30.8% ), and needle aspiration cytology or post resection pathological examination in 14 cases (53.8% ). Paget disease consisted of simple papillary Paget disease in 3 cases (11.5%), ductal carcinoma in 18 cases (69.2%) and invasive ductal carcinoma in 5 cases (19.2%). Pathological TNM staging was 0 stage in 19 cases (73.1%), stageⅠin 3 cases (11.5%), stageⅡin 2 cases (7.7%), stageⅢin 2 cases (7.7%) and no stage inⅣcase. In this group, 2 cases underwent radical mastectomy, 18 cases underwent modified radical mastectomy, 4 cases underwent simple mastectomy, and 2 cases underwent mastectomy combined with low axillary lymph node dissection and intraoperative rapid frozen examination. Fourteen patients received adjuvant chemotherapy with CEF(cyclophosphamide + pharmorubicin + tegafur)/EC (pharmorubicin + cyclophosphamide) + T(docetaxel) or TP(docetaxel + cis- platinum)regiment after operation, 2 cases were treated with trastuzumab targeted therapy and 5 cases with adjuvant radiotherapy. Twenty-five of 26 patients were followed up for 8-108 months except one patient lost in follow-up. The 5-year survival rate was 96.0% (24/25), and the 10-year survival rate was 52.0% (13/25). Conclusions The diagnosis of Paget disease of the breast depends on cytology or pathology, and multidisciplinary treatment based on surgery is judged of by tumor stage and coincident other types of breast cancer and axillary lymph node involvement.

Objective To investigate the clinicopathological features of abdominal lymphangioma and its diagnosis and treatment.Methods The clinical data of 37 patients with abdominal lymphangioma were analyzed retrospectively.Results The clinical presentations were slight abdominal distention and discomfort in 6 cases (16％),abdominal pain or lumbago in 13 cases (35％),found by health screening in 14 cases (38％) and abdominal mass in 4 cases (11％).Tumor located in retroperitoneal space in 20 cases,small bowel in 7 cases,colon mesentery in 4 cases,small mesentery in 2 cases,duodenum in 2 cases,stomach in one case and pancreas in one case.The surgical procedures were complete resection in 31 cases and incomplete resection in 6 cases.Except 3 cases lost to fol]ow-up,no recurrence was found during the postoperative follow-up period.Conclusions It is difficult to diagnose abdominal lymphangioma before operation,and complete resection of tumor is the first choice.

Objective To investigate the clinical characteristics,surgical treatment and outcome for patients with duodenal stromal tumor.Methods Data of 40 patients with stromal tumor of duodenum were reviewed retrospectively.Results All patients received resection including local resection in 14 cases,segmental resection of the duodenum in 17 cases,and pancreaticoduodenectomy in 9 cases.38 cases were followed-up,and two were lost.The median follow-up was 59 months (range 3-240 mos).The 1,3,and 5-year overall survival rates were 92％,76％ and 68％,respectively.No recurrence was found in very-low-risk tumor (n =1) and low-risk turmors (n =4).The 1,3,and 5-year overall survival rates for intermediate-risk tumors were 95％,80％ and 70％,respectively;and those were 69 ％,31％,and 0 for high-risk tumors,respectively.14 of 33 cases (42％) suffered from recurrence after radical resection for intermediate or high-risk tumors.33 postoperative cases received treatment with Imatinib (Glivec) for more than one year,and one case developed recurrence at 2.5 years after operation.4 patients with synchronous liver metastasis received palliative resection and Imatinib,and two survived more than 1 year.Conclusion Surgery is the first choice for duodenal stromal tumor,and Imatinib should be administered for high-risk disease after surgery.

Objective To evaluate the effect of plastic surgery for scar contracture after hand burn.Methods Clinical treatment data of 56 patients with scar contracture after hand burn was collected from December 2011 to December 2016.Different surgery methods were adopted to treat the scar contracture after hand burn according to different degree,different sites and different range.Results All cases were operated successfully,and the appearance and function of the hands were almost recovered during the 6 months' follow-up,without contracture again.Conclusion Appropriate surgical programs should be used in scar contracture with different parts and degrees,and reasonable postoperative rehabilitation can improve the function and appearance of hands better,which can avoid secondum contracture.