Objective To study the effect of urodynamic factors on the urinary retention of the patients with cervical cancer received radical hysterectomy. Methods Seventy-two patients with cervical cancer Ininternational Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ bl to Ⅱ a hospitalized in Fujian Provincial Maternity and Child Health Hospital between June 2006 and August 2009, who were not found any abnormal representation of urodynamics before the operation, were divided into the group with urinary retention and the group without urinary retention based on whether urinary retention after the operation. All patients were detected by urodynamic examination following radical hysterectomy. Data obtained from urodynamic examination were analysed by logistic regression to evaluate the influence of urodynamic factors on the urinary retention postoperation. Results Twenty-one patients out of all were found with urinary retention after the operation , the incidence rate of urinary retention was 29%. The first sensation after operation in both groups were increased significantly than those before operation[ ( 171 ±61 )ml vs.(126 ±28)ml, (134±39)ml vs. (119 ± 17)ml,all P＜0.05], while the maximum volume[ (337 ±66) and (300 ±66)ml, respectively], the compliance[ (31 ±25) and (29 ± 18) ml/cm H2O (1 cm H2O =0. 098 kPa), respectively], the maximum flow rate[ (10 ±4) and (12 ±5) ml/s, respectively] and the pressure at the maximum flow rate [ (27 ±9) and (32 ±8) cm H2O, respectively] were decreased obviously after radical hysterectomy in both the group with urinary retention and the group without urinary retention ( all P ＜0.05), compared with the corresponding value before the operation. The urodynamic changes in urinary retention group was much more severe than those in group without urinary retention ( P ＜ 0. 05 ). The single factor analysis results showed that bladder destusor dysfunction ( OR = 8. 20, 95% CI: 2.62 - 25. 66, P ＜0. 01 ) and lack of sensation ( OR = 6. 90, 95% CI: 1.95 - 24. 43, P ＜ 0. 01 ) were relevant to the urinary retention post-operation. While there were not relationship was found between low compliance bladder( OR =1.99, 95% CI:0. 70 - 5.63, P = 0. 195 ), detrusor overactivity ( OR = 2. 51, 95% CI: 0. 73 - 8.67, P =0. 144), bladder outlet obstruction ( OR = 3.77, 95% CI: 0. 76 - 18. 57, P = 0. 104 ) or dyssynergia of urethral external sphincter( OR =2. 67, 95% CI:0. 49- 14. 45, P =0. 255 ) and urinary retention following the operation. There were an antagonistic effects ( OR = 7.60, 95% CI: 1.43 - 40. 39, P = 0. 017 ) of detrusor overactivity and bladder destrusor dysfunction on urinary retention. The multiple factors analysis results revealed that bladder destusor dysfunction( OR = 7.01, P ＜ 0. 01 ) and lack of sensation( OR = 5.45, P =0. 018)were the independent risk factors influening on the urinary retention post-operation. Conclusions There are obvious urodynamic change in cervical cancer patients following radical hysterectomy. Bladder destrusor dysfunction and lack of sensation are the independent urodynamic risk factors influencing on urinary retention following radical hysterectomy, while detrusor over activity may be a protective effect on bladder destrusor dysfunction post-operation in some degree. Urodynamic test is important for analysis and treatment of urinary retention following radical hysterectomy.

Objective To evaluate the value of MSCT in the diagnosis of extrahepatic cholangiocarcinoma.Methods The MSCT appearances of extrahepatic cholangiocarcinoma confirmed by pathology in 27 cases were analyzed retrospectively.Among them,20 patients underwent plain and four-phase dynamic contrast-enhanced CT scans including early arterial phase,late arterial phase,portal phase and delay phase,7 patients only underwent contrast-enhanced CT scans.Results 15 lesions were located in the hilar and 12 lesions were located in the common bile duct.CT features of cholangiocarcinomas in this group were varied with its position and growth pattern.Besides the direct sign such as delay enhancement,the indirect findings were also specific such as hepatic lobe atrophy,dilated bile duct,etc.Conclusion MSCT is of great value in diagnosis of extrahepatic cholangiocarcinoma.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

Objective To analysis the short-term quality of life and clinical outcome of early enteral immunonutrition(EIN)used after operation in patients with totally endoscopic esophagectomy.Methods This randomized controlled trial enrolled 110 patients receiving totally endoscopic esophagectomy in department of thoracic surgery of the fourth hospital of Hebei medical university between May 2015 and November 2016.The patients were randomly divided into enteral immunonutrition group (EIN group,n =56) and parenteral nutrition group (PN group,n=54).The scale scores of quality of life,the time of first postoperative anal exhaust,the time of removal of drainage tube,the number of postoperative infections and the length of hospitalization were compared between the two groups before operation and after operation.Results (1) There were no significant differences in age,gender,education,marital status,tumor location,clinical stage,intraoperative bleeding between the two groups (P＞0.05).(2) There were no significant differences in the quality of life before operation (P＞0.05);All functional scale scores of EIN group were significantly higher than PN group (P＜0.05),while the symptom scale score were significantly lower than PN group(P＜0.05).(3) There were significant differences in the time of first postoperative anal exhaust,the time of removal of drainage tube,the number of postoperative pneumonia compliCations and the length ofhospitalization in the two groups (P＜ 0.05).There was no significant difference in the incidence of anastomotic fistula between the two groups(x2=0.621,P=0.431 4) The scale scores of quality of life (the overall health status as the representative) had a negatively linear relationship with the clinical outcome(P =0.000),the absolute value of correlation coefficient in EIN group was higher than that in PN group.The higher score of the quality of life,the shorter time of the postoperative anal exhaust,removal of drainage tube and the length of hospitalization.Conclusion Enteral immunonutrition can improve the quality of life,improve the prognosis and promote the rapid recovery of patients with totally endoscopic esophagectomy.

Objective:To investigate the clinical application of Grunenwald incision in cervicothoracic junction surgery.Methods:The clinical data of 25 patients with cervicothoracic junction tumor and 1 patient with cervicothoracic junction trauma in the single treatment group of Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2011 to September 2021 were analyzed retrospectively, including 19 males and 7 females, aged 9-73 years old. Among the 26 patients, there were 9 cases of upper mediastinal tumor, 6 cases of superior sulcus tumor, 4 cases of thyroid tumor invading the upper mediastinal, 4 cases of chest wall tumor, 2 cases of esophageal cancer combined with supraclavicular lymph node metastasis, and 1 case of foreign body penetrating injury at the cervicothoracic junction. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision, neck collar incision were used in all patients. The degree of tumor resection was evaluated. The operation time, intraoperative blood loss, length of hospital stay were observed, and the postoperative follow-up was analyzed.Results:There was no perioperative death in the whole group. 14 cases were treated with Grunenwald incision alone, 6 cases with additional posterolateral chest incision, 4 cases with additional neck collar incision, and 2 cases with additional median sternal incision. The tumors were completely resection in 22 cases, palliative tumor resection in 3 cases, and complete foreign body removal in 1 case. Postoperative pathology included 4 cases of schwannoma; 3 cases of lung adenocarcinoma, thyroid cancer and myofibroblastoma, respectively; 2 cases of supraclavicular lymph node metastasis of esophageal cancer and lung squamous carcinoma, respectively; 1 case of large cell neuroendocrine carcinoma, metastatic carcinoma of the first rib after lung squamous cell carcinoma, ganglioneuroma, nodular goiter, hemangioma, well differentiated liposarcoma, vascular endothelial tumor and cavernous angioma, respectively. The operation time was 120-430 min, with a mean of(226.92±88.40)min. The intraoperative blood loss was 100-1 000 ml, with a mean of(273.46±196.34)ml. The length of hospital stay was 6-26 days, with a mean of(12.73±4.46 )days. 26 patients were followed up for 6-130 months, with a mean of(57.88±43.64) months. During the follow-up period, 6 patients died.Conclusion:Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumors, high rib resection, and cervicothoracic junction trauma.

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

OBJECTIVE： To observe the effects of stilbene glycosidec （TSG） on okadaic acid （OA）-induced Tau protein phosphorylation in NG108-15 cells， and to investigate the potential anti-Alzheimer’s disease （AD） mechanism of this compound. METHODS： AD model of NG108-15 cells was induced by OA. The survival rate of NG108-15 cells was observed by MTT assay after pretreated with low-dose， medium-dose and high-dose of TSG （50， 100， 200 μmol/L）. The apoptosis of NG108-15 cells was detected by AO/EB double fluorescence staining. The protein and mRNA expression of CDK5 and GSK3β， and the protein expression of Tau and p-Tau were detected by Western blotting assay and RT-PCR. The distribution of CDK5， GSK3β and Tau protein were detected by immunofluorescence. RESULTS： The normal morphology of NG108-15 cells was observed in normal control group， but CDK5， GSK3β and Tau protein were not found or few was found. Contracted or globular early apoptotic cells were observed in model gorup； the distribution of CDK5， GSK3β and Tau protein was increased， while survival rate of the cells was decreased； protein and mRNA expression of CDK5 and GSK3β as well as ratio of the relative expression of p-Tau to that of Tau （p-Tau/Tau） were all increased significantly （P＜0.05 or P＜0.01）. After pretreatment of TSG， the distribution of early apoptotic cells as well as CDK5， GSK3β and Tau protein were all decreased to some extent in administration groups， while survival rates of the cells were increased significantly. Protein expression of CDK5 and p-Tau/Tau in medium-dose group and high-dose group as well as mRNA expression of CDK5， protein and mRNA expression of GSK3β in administration group were decreased significantly （P＜0.05）. CONCLUSIONS： TSG can protect against AD model cells， the effects of which may be associated with improving survival rate of the cells， down-regulating the protein expression and gene transcription level of phosphokinase CDK5 and GSK3β， inhibiting Tau protein phosphorylation.

OBJECTIVE：To study the regulatory effects of stilbene glucosid e（TSG）on c-Jun N-terminal kinase （JNK）and protein phosphortase 2B（PP2B）in APP/PS1/Tau transgenic dementia （3×Tg-AD）mice，and to explore its potential mechanism of anti-Alzheimer’s disease （AD）. METHODS ：Totally 45 male 3×Tg-AD mice were randomly divided into model group ，positive control group （huperzine A ，0.15 mg/kg），TSG low-dose ，medium-dose and high-dose groups （0.033，0.1，0.3 g/kg），with 9 mice in each group. Another 9 normal male C 57BL/6J mice were included into normal control group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 60 d. Normal control group and model group were given constant volume of normal saline intragastrically. After medication ，Morris water maze experiment was used to test the spatial learning and memory ability of mice in each group ；Nissl staining was used to observe the changes of Nissl bodies in cerebral cortex and hippocampus ；mRNA and protein expressions of JNK and PP 2B were detected by qRT-PCR and Western blotting assay. RESULTS：Compared with normal control group ，the escape latency was significantly prolonged （P＜0.01），the retention time of the original platform quadrant was significantly shortened （P＜ and the times of crossing the platform was significantly reduced in model group （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was significantly 729011126@qq.com reduced，the staining was slight ；the relative expressions of JNK mRNA and protein were significantly increased （P＜ 0.01），and the relative expressi ons of PP 2B mRNA and protein were significantly decreased （P＜0.01）. Compared with model group ，the escape latency was significantly shortened in positive control group and TSG groups （P＜0.01）；the retention time of the original platform quadrant was significantly prolonged （P＜0.01）；the times of crossing the platform was significantly increased （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was increased significantly ，the staining was heavy ；the relative expression of JNK protein was significantly decreased（P＜0.05 or P＜0.01），the relative expressions of PP 2B mRNA and protein were significantly increased （P＜0.01）， while the relative expression of JNK mRNA was significantly decreased in TSG high-dose group （P＜0.05）. CONCLUSIONS ：TSG can improve the learning and memory ability and neuronal damage of 3 × Tg-AD mice. The mechanism may be related to down-regulating the transcription and expression of protein kinase JNK ，up-regulating the transcription and expression of protein phosphatase PP 2B.

BACKGROUND: Video assisted thoracic surgery (VATS) is the main surgical method for lung cancer. The aim of this study was to analyze the reasons for conversion to thoracotomy in 83 cases among 1,350 consecutive cases who underwent video-assisted thoracic surgery (VATS) lobectomy by a single surgical team, in order to achieve a deeper understanding of the rules and the opportunity for conversion to thoracotomy in VATS lobectomy under normal conditions. METHODS: The clinical data of 1,350 patients who underwent VATS lobectomy between September 21, 2009 and June 1, 2020, by a single surgical team in the Fifth Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. There were 773 males and 577 females, aged 8-87 years, with a median age of 61.3 years, including 83 cases of benign diseases, 38 cases of lung metastases, and 1,229 cases of primary lung cancer. The cases with stage I, II and IIIa were 676, 323 and 230, respectively. The cases of left upper, left lower, right upper, right middle, right lower, right middle and upper and right middle and lower lobectomy were 301 (22.30%), 231 (17.11%), 378 (28.00%), 119 (8.81%), 262 (19.41%), 16 (1.19%) and 43 (3.19%), respectively. RESULTS: In the cohort of 1,350 consecutive patients with VATS lobectomy, 83 patients (6.15%) were converted to thoracotomy for different reasons. The conversion rate of benign lesions was significantly higher than that of malignant tumors (P<0.05). The conversion rate in stage IIIa was significantly higher than that in stage I and II (P<0.05). The conversion rate of combined lobectomy was significantly higher than that of single lobectomy (P=0.001). The conversion rate of left upper lobectomy was significantly higher than that of other single lobectomy (P<0.001). The conversion rate of right middle lobectomy was significantly lower than that of other single lobectomy (P=0.049). The main reasons for conversion were vascular injury (38.55%), lymph node interference (26.51%) and dense adhesion in thoracic cavity (16.87%). In the conversion group, the total operation time was (236.99±66.50) min and the total blood loss was (395.85±306.38) mL. The operation time in patients converted to thoracotomy due to lymph node interference was (322.50±22.68) min, which was significantly longer than that in the other groups (P<0.05). The intraoperative blood loss in patients converted to thoracotomy due to vascular injury was (560.94±361.84) mL, which was significantly higher than that in the other groups (P<0.05). With the increase in surgical experience, the number of vascular injuries gradually decreased at the early stage, mid-stage and late stage (P=0.045). CONCLUSIONS In VATS lobectomy, benign lung lesions and more advanced malignant tumors led to more surgical difficulties and higher conversion rate. The conversion rate was different in different lobectomy sites, with the highest in left upper lobectomy, and the lowest in right middle lobectomy. Vascular injury, lymph node interference and dense adhesion were the main reasons for conversion to thoracotomy, which led to prolonged operation time and increased blood loss. With the increasing number of surgical cases, the rate of conversion to thoracotomy in VATS lobectomy continues to decline, which may be mainly due to the more advanced treatment of pulmonary vessels.