Cell-free DNA (cfDNA) is the DNA fragment existing in human extracellular fluid. In specific physiological process (such as pregnancy) or pathological conditions (such as human malignancies), the contents of cfDNA in extracellular fluid will abnormally change. The contents and molecular characteristics of cfDNA make it have the potential as a kind of biomarker for diseases′ diagnosis. With the development of cfDNA detection technology such as sequencing and mass spectrometry, liquid biopsy based on cfDNA detection has been widely used in clinical tumor diagnosis, tumor treatment, prenatal examination, and research in autoimmune diseases. A systematic summary of the latest research progress in the development of cfDNA detection technology and the clinical application of liquid biopsy, as well as the research progress of cfDNA in the diagnosis and treatment of related diseases is summarized in this review.

Lymphoedema of lower extremities,chronic and progressive,will severely deteriorate the quality of life of patients as it progresses.Thus,early diagnosis and treatment to delay the progress of the disease is conducive to improving the prognosis of patients.At present,common techniques for the diagnosis of lower limb lymphedema,whose advantages and disadvantages vary,cannot be applied to individual case comprehensively.CEUS has the advantages of non-invasion,convenience,real-time,and good repeatability for this disease.CEUS can enhance the image of lymph in lymphatics,and has a high sensitivity to superficial lymphatics,gradually applied in lymphedema of lower limbs.This article reviews the application of CEUS in lower limb lymphedema.

Chronic aortic stenosis and regurgitation can cause left ventricular remodeling.Whether these changes are reversible and their reversibility after valve replacement are the main determinants affecting the timing and prognosis of surgery.Imaging techniques are commonly used to evaluate myocardial structure and function,in which echocardiography and enhanced CT are helpful to evaluate artificial flap function and monitor left ventricular deformation,while cardiac MR and PET/CT are helpful to identify the progression and regression of postoperative cardiac fibrosis.The combined application of these new techniques can improve clinical outcomes by early diagnosis and non-invasive detection of postoperative left ventricular reverse remodeling.This paper reviews the evaluation and application of multi-modal imaging techniques for left ventricular reverse remodeling after aortic valve replacement.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

Objective:To explore the effect of previous intestinal resection on anastomotic fistula within 30 days after surgery in Crohn′s disease.Methods:The clinical data from 92 Crohn′s disease patients who underwent intestinal resection and anastomosis at the Department of General Surgery in Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine from Jan 2016 to Sep 2019. Patients were divided into no previous intestinal resection group ( n=45) and previous intestinal resection group ( n=47). The relationship between previous intestinal resection and postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis was analyzed. Results:A total of 11 cases (12% leak rate) underwent postoperative anastomotic leak. There were 2 leaks in patients with no previous history of intestinal resection, while 9 leaks in patients with previous bowel resection (χ 2 =4.722, P=0.03). The OR of the postoperative anastomotic leak in Crohn′s disease patients with previous intestinal resection compared with no previous intestinal resection group was 5.092 (95% CI: 1.035-25.048). Patients with 1 previous resection (24 cases) had a leak rate of 13%, whereas patients with >1 previous resection episodes (23 cases) had a leak rate of 26%. The number of previous resection episodes correlated with an increasing risk for clinical anastomotic leak (correlation coefficien r=0.995). Conclusions:Previous intestinal resection is an independent risk factor for ensuing postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis.

Objective: To compare the efficacy of modified pancreaticojejunostomy with traditional pancreaticojejunostomy following pancreaticoduodenectomy, and to investigate the risk factors of postoperative pancreatic fistula. Methods: Clinical data of 68 patients who underwent pancreaticoduodenectomy between October 2017 and October 2018 at the Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital was retrospectively collected and analyzed.According to the method of pancreaticojejunostomy, the patients were divided into two groups: modified pancreaticojejunostomy group (34 patients) and traditional pancreaticojejunostomy group (34 patients). There were 18 males and 16 females, aged (60.4±9.6) years of modified pancreaticojejunostomy groups; there were 17 males and 18 females, aged (58.9±10.9) years of traditional pancreaticojejunostomy group. The major postoperative complications such as pancreatic fistula were compared between the two groups, and the risk factors of postoperative pancreatic fistula were analyzed by univariate and multivariate analyses. Results: All of the 68 operations were successfully completed. The overall incidence of postoperative complications was 51.5% (35/68). The incidence of postoperative pancreatic fistula was 13.2% (9/68), of which all were cases of grade B.There were 16 patients (23.5%) occurred with abdominal infection, and 11 patients (16.2%) occurred with delayed gastric emptying, including 1 case of grade A, 1 case of grade B and 9 cases of grade C.And 9 patients (13.2%) occurred with postoperative bleeding was, including 2 cases of mild bleeding, 5 cases of moderate bleeding, and 2 cases of severe bleeding.Biliary leakage occurred in one patient (1.5%) and chylous leakage occurred in two patients (2.9%). The modified pancreaticojejunostomy could significantly reduce the incidence of postoperative bleeding compared with control group (χ²=4.610, P=0.032). And there were no significant differences for other postoperative complications between the two groups (all P>0.05). According to the results of univariate analysis: age, intraoperative bleeding and diameter of pancreatic tube were related factors affecting postoperative pancreatic fistula (P=0.025, 0.019, 0.017, respectively). The results of multivariate analysis showed that intraoperative bleeding>400 ml and diameter of pancreatic tube <3 mm were independent risk factors of pancreatic fistula following pancreaticoduodenectomy (P=0.025, 0.008, respectively). Conclusion The modified pancreaticojejunostomy is feasible with advantages of reducing postoperative bleeding following pancreaticoduodenectomy.

Objective To investigate the effects of the extent of regional lymph node dissection on the prognosis of patients with T4 gallbladder carcinoma.Methods The retrospective cohort study was conducted.The clinicopathological data of 64 patients with T4 gallbladder carcinoma who underwent radical cholecystectomy in the 4 medical centers between January 2013 and December 2016 were collected,including 31 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,16 in the First Affiliated Hospital of Xi'an Jiaotong University,11 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 6 in the Affiliated Hospital of North Sichuan Medical College.There were 27 males and 37 females,aged from 35 to 77 years,with a median age of 59 years.Sixty-four patients underwent radical cholecystectomy and regional lymph node dissection.According to the extent of intraoperative lymph node dissection,25 patients (13 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,6 in the First Affiliated Hospital of Xi'an Jiaotong University,4 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 2 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct,hepatoduodenal ligament,back of head of pancreas,next to common hepatic artery and celiac trunk were allocated into the extended dissection group,39 patients (18 in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University,10 in the First Affiliated Hospital of Xi'an Jiaotong University,7 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine and 4 in the Affiliated Hospital of North Sichuan Medical College) whose extent of lymph node dissection involved lymph nodes next to cystic duct and hepatoduodenal ligament were allocated into the control group.Observation indicators:(1) postoperative complications;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival up to January 2018.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated with the independentsample t test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test and Fisher exact probability.The survival curve was drawn using the KaplanMeier method,and the comparison of survival rates was done by the Log-rank test.Results (1) Postoperative complications:64 patients with T4 gallbladder carcinoma underwent successful radical cholecystectomy and regional lymph node dissection,without intraoperative death.Twelve patients had different degrees of postoperative complications.Four of 7 patients undergoing extended radical cholecystectomy had postoperative complications.Twenty-five patients in the extended dissection group were cured by conservative treatment,including 4 with intraperitoneal infection and 2 with pancreatic leakage,with a complication incidence of 24.0％ (6/25).Thirtynine patients in the control group were cured by conservative treatment,including 5 with intraperitoneal infection and 1 with gastric retention,with a complication incidence of 15.4％ (6/39).There was no statistically significant difference in the complication incidence between the two groups (x2=0.284,P＞0.05).(2) Follow-up and survival situations:64 patients were followed up for 1-60 months.The postoperative overall median survival time was l l months.The postoperative median survival time,1-,3-and 5-year cumulative survival rates were respectively 18 months,80％,16％,9％ in the extended dissection group and 8 months,21％,4％,0 in the control group,with a statistically significant difference in the prognosis between the two groups (x2=14.744,P＜ 0.05).Conclusions On the premise of practiced surgical skill,extended regional lymph node dissection cannot increase incidence of surgical complication in patients with T4 gallbladder carcinoma after radical resection.Actively extending lymph node dissection up to near common hepatic artery,peri-celiac trunk and back of head of pancreas can improve long-term survival and prognosis.

Objective: To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital-cervical fusion system in single stage. Methods: Thirty-seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3±12.3) years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, clivus-canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t-test. Results: The mean JOA score of the patients increased from 10.5 to 14.4 at the one-year follow-up(t=14.3, P=0.00). Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus-canal angle improved from (118.0±6.5) degrees preoperative to (143.7±5.0) degrees postoperative(t=6.2, P=0.00). Shrinkage of the syrinx was observed 1 week after surgery in 24 patients, and 6 months in 31 patients.Twenty-eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One-side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness, and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital-cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.