Gallbladder cancer(GBC)is a relatively rare malignant tumor with poor prognosis,which is usually diagnosed in the late stage due to the lack of obvious early symptoms and specific clinical manifestations.Surgery is the only possible cure for gallbladder cancer,but the choice of surgical approach and scope is still controversial.In recent years,the application of targeted therapy and immunotherapy in advanced gallbladder cancer has brought new hope to patients.This article reviews the epidemiologic features,risk factors,pathologic characteristics,and current diagnostic and therapeutic strategies of gallbladder cancer,and discusses several controversial topics,aiming to provide a reference for clinical management.

Gallbladder cancer(GBC)is a relatively rare malignant tumor with poor prognosis,which is usually diagnosed in the late stage due to the lack of obvious early symptoms and specific clinical manifestations.Surgery is the only possible cure for gallbladder cancer,but the choice of surgical approach and scope is still controversial.In recent years,the application of targeted therapy and immunotherapy in advanced gallbladder cancer has brought new hope to patients.This article reviews the epidemiologic features,risk factors,pathologic characteristics,and current diagnostic and therapeutic strategies of gallbladder cancer,and discusses several controversial topics,aiming to provide a reference for clinical management.

Objective:To prepare specific molecular probe 18F-AlF-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid-(polyethylene glycol) 4-ZD2 ( 18F-AlF-NOTA-PEG 4-ZD2) for targeting extradomain-B fibronectin (EDB-FN), and evaluate its properties in vitro and in vivo. Methods:18F-AlF-NOTA-PEG 4-ZD2 was prepared by one-step chelation labeling with Al 18F. The radiochemical purity and in vitro stability were determined by high performance liquid chromatography (HPLC). The partition coefficient (logP) of 18F-AlF-NOTA-PEG 4-ZD2 was evaluated, and the cell uptake experiment was carried out (triple-negative breast cancer (MDA-MB-231) cells (1×10 6/tube) were divided into 3 groups ( n=3 per group); positive group, inhibition group, control group). MicroPET imaging was performed on MDA-MB-231 bearing nude mice ( n=3) after 18F-AlF-NOTA-PEG 4-ZD2 injection (30, 60, 90, 120 min) and compared with blocking group ( n=3, NOTA-PEG 4-ZQ 2 was preinjected at 0.5 h before 18F-AIF-NOTA-PEG a-ZD2 injection). Independent-sample t test was used to analyze the data. Results:18F-AlF-NOTA-PEG 4-ZD2 was successfully prepared. The optimized radiochemical yield was (33.8±2.1)% (undecay corrected, n=8) and the radiochemical purity was >96%. After incubating 120 min at 37 ℃, the radiochemical purity of 18F-AlF-NOTA-PEG 4-ZD2 in human serum and PBS was >93%, indicating its good stability in vitro. The specific activity was (11.1±3.2) GBq/μmol, and logP was -1.43±0.05. The uptake value of tumor cells was (1.77±0.28) percentage applied activity (%AR)/10 6 cells at 120 min post-injection in positive group, and the total uptake value of the inhibition group was (0.76±0.07) %AR/10 6 cells ( t=4.30, P=0.032). MicroPET imaging in tumor bearing nude mice showed that 18F-AlF-NOTA-PEG 4-ZD2 was mainly metabolized by the liver and kidneys. The tumor uptake value was (1.94±0.21) percentage activity of injection dose per gram of tissue (%ID/g) at 60 min post-injection and the tumor/muscle ratio was 3.80±0.25 at 90 min post-injection in the experimental group, while the tumor uptake value of tumor bearing nude mice in the blocking group was (0.43±0.09) %ID/g at 60 min post-injection ( t=3.18, P=0.006). Conclusions:18F-AlF-NOTA-PEG 4-ZD2 can be prepared simply with high labeling rate and good stability in vitro, with high tumor uptake and tumor/muscle ratio in microPET imaging, and good specificity and long tumor residence time. The probe has good application prospect in breast cancer with high expression of fibronectin subtype EDB-FN.

Objective:To analyze the relationship between red cell distribution width (RDW) and disease severity in patients with non-ST-elevation myocardial infarction.Methods:Seventy patients with non-ST-elevation myocardial infarction who received treatment in Chaozhou People's Hospital from June 2019 to June 2020 were included in the observation group. An additional 70 patients with ST-elevation myocardial infarction who concurrently received treatment in the same hospital were included in the control group. All patients underwent electrocardiography and blood biochemical index examination. RDW was compared between the observation and control groups. The relationship between RDW and the severity of non-ST-elevation myocardial infarction was analyzed.Results:RDW in the observation group was significantly higher than that in the control group [(14.60 ± 1.00) % vs. (13.06 ± 1.70) %, t = 5.884, P = 0.012). The detection rate of coronary artery thrombosis in the observation group was significantly higher than that in the control group [70.00% (49/70) vs. 50.00% (35/70), χ2 = 7.563, P = 0.002]. In the observation group, the area under the receiver operating characteristic (ROC) curve plotted taking RDW as the variable was 0.649 (95% CI 0.546-0.753, P = 0.006). When the critical value of RDW was 14%, the sensitivity and specificity of RDW in the prediction of non-ST-elevation myocardial infarction were 73% and 59% respectively. RDW was positively correlated with cardiac troponin I level ( r = 0.19, P = 0.006). Conclusion:In patients with non-ST-elevation myocardial infarction, the increase in RDW is related to myocardial injury and the increase in cardiac troponin I level. RDW can be used as an effective index to predict the severity of non-ST-elevation myocardial infarction.

Objective To investigate the curative effect of Sandplay therapy on attention deficit hyperactivity disorder (ADHD)preschool children co - morbid sleep disorder. Methods According to the random number generated by EXCEL software's RAND function,a total of 62 ADHD children co - morbid sleep disorder were randomly divi-ded into experimental group(n = 31)and control group (n = 31). The control group was treated with family behavior therapy and the experimental group was treated with sandplay therapy based on the family behavior therapy. With the Achenbach Child Behavior Check List (CBCL),Conners Parent Symptom Questionnaire (PSQ),Conner Concise Questionnaire (Conners Abbreviated Symptom Questionnaire,ASQ)and Children′s Sleep Habit Questionnaire(CSHQ),the overall curative effect was evaluated before and after treatment by their scores. Results The results of independent - samples t test showed that the scores of PSQ′s all factors,ASQ′s and CBCL′s total score,CSHQ′s total score and all factors had no significant difference between the two groups before the intervention (t conduct problem = - 0. 847,t learning problems =0. 504,t psychosomatic disorder = - 1. 008,t hyperactivity/ impulsion = - 0. 331,t anxiety = 0. 690,t hyperactivity index = 0. 757,t CBCL′s total score =- 0. 532,t ASQ′s total score = 0. 514,t CSHQ′s total score = 1. 132,t sleep impedance = - 0. 767,t sleep latency = - 0. 634,t sleep duration = 0. 150, tsleep anxiety = 0. 149,t sleep wake = 0. 417,t sleep disorder = 0. 709,t sleep apnea = 0. 950,t daytime sleepiness = 1. 530,all P > 0. 05). The scores of PSQ′s all factors,ASQ′s and CBCL′s total score,sleep impedance,sleep latency,sleep duration,sleep wake, daytime sleepiness and CSHQ′s total score all had significant differences between the two groups after the intervention(t conduct problem = - 3. 982,t learning problems = - 2. 258,t psychosomatic disorder = - 2. 470,t hyperactivity/ impulsion = - 4. 377,t anxiety =- 2. 684,t hyperactivity index = - 4. 249,t CBCL′s total score = - 3. 982,t ASQ′s total score = - 5. 576,t sleep impedance = - 3. 712,t sleep latency =- 2. 947,t sleep duration = - 2. 332,t sleep wake = - 6. 031,t daytime sleepiness = - 6. 256,t CSHQ′s total score = - 6. 706,all P < 0. 05). The results of analysis of variance of repeated measurement showed that PSQ behaviour problem,psychosomatic disor-der,hyperactivity and hyperactivity index scores of the main effects of intervention had significant difference (F conduct problem = 4. 966,F psychosomatic disorder = 5. 176,F hyperactivity/ impulsion = 4. 949,F hyperactivity index = 4. 926,all P < 0. 05);the main intervention effects of ASQ and CBCL′s total score had statistical difference (F CBCL = 4. 398,F ASQ = 4. 814,all P < 0. 05);the main intervention effects of sleep impedance,sleep duration,sleep wake and CSHQ′s total score had statistical difference (F sleep impedance = 5. 697,F sleep duration = 4. 467,F sleep wake = 6. 610,F CSHQ′s total score = 6. 016,all P <0. 05). There were significant differences in the characteristics of the initial sand table and the final sand table in the experimental group [traumatic subject:(4. 48 ± 1. 55)cases vs. (1. 23 ± 0. 81)cases,t = 8. 247;curing subject:(1. 77 ± 1. 09)cases vs. (4. 55 ± 1. 46)cases,t = 11. 274,all P < 0. 05]. Conclusion Sandplay therapy can effectively improve the core symptoms of preschool ADHD children co - morbid sleep disorders,which can be used as an early in-tervention.

ObjectiveTo explore the characteristics and correlation of intelligence development and socioemotional development in 1~3 years old children with expressive language disorder,and provide a basis for early intervention.Methods125 cases with expressive language disorder(language disorder group) and 126 normal children (normal group) are evaluated in two parts (intelligence and social mood) with 0~6 years old neuropsychological development diagnosis scale and Chinese version of urban infant-toddler social and emotional assessment.Results (1)The scores in language disorder group were lower than normal group in the area of free movements (81.60±10.40 vs 89.62±7.94),adaptability (81.48±10.95 vs 91.25±8.89),language (67.46±7.20 vs 89.13±8.24),social behavior (76.61±9.73 vs 90.12±8.13) and total developmental quotient (80.17±6.39 vs 91.15±6.05) (P<0.05).(2) There were significant differences between language disorder group and normal group in the area of externalizing behavior(56.28±10.15 vs 53.57±7.91),deregulation (56.45±10.61 vs 51.11±9.32) and capabilities(46.79±9.08 vs 51.25±7.47) (P<0.05).The boys' scores in internalizing behavior were lower than the girls' (49.19±10.76 vs 54.71±9.90) (P<0.05).(3) The scores of gross motor had positive correlation with externalizing behavior (r=0.220,P<0.05).The scores of language had negative correlation with externalizing behavior and deregulation(r=-0.650,P<0.05;r=-0.470,P<0.05).The scores of social behavior had negative correlation with externalizing behavior (r=-0.208,P<0.05).There was also a negative correlation between total development and deregulation (r=-0.184,P<0.05).(4) Multiple stepwise linear regression results showed that the externalizing behavior domain and mothers' education could predict 44.1% of variances in the language area.ConclusionThe children with expressive language disorder not only show backward in level of language development,but also in the development of other areas,and also bad social behavior and emotional problems.Individualized parenting interventions should be adopted to promote these children's intelligent development in an all-round way.

Objective To investigate the effect of autologous peripheral blood stem cell transplanta-tion combined with CD34 + cells and oral sarpogrelate hydrochloride for the treatment of vascular reconstruc-tion and blood supply on the thromboangiitis obliterans. Methods Thromboangiitis obliterans ( TAO) of 262 patients with 262 lower limbs were divided into stem cells CD34 + cells transplantation combined with sarpogrelate hydrochloride group ( group A) with 100 lower limbs, CD34 + stem cell transplantation group ( group B) with 91 lower limbs, and sarpogrelate hydrochloride oral group ( group C) with 71 lower limbs. The degree of lower limb local blood flow variability were calculated at the three levels of skin, blood vessels and blood by preoperative and postoperative use of multi-function monitoring instrument, Doppler detector, transcutaneous oxygen pressure monitor, and digital subtraction angiography ( DSA) , respectively. Results⑴ The degree of shank, foot cyanosis, cool skin, and pain was relieved significantly in groups A and B than in group C for 1 month after the treatment (P<0. 05). ⑵Intermittent claudication distance, the skin temperature of the lower leg and foot to patients in the groups A and B than in group C, with a significant difference (F=7. 01, F=7. 04, P<0. 05) for 3 months after the treatment. ⑶ Among the patients with amputation, 10 cases were in group A, 16 cases in group B, and 31 cases in group C for 6 months after the treatment. ⑷ Transcutaneous oxygen pressure was increased from ( 30. 43 ± 4. 31 ) mmHg to ( 37. 21 ± 9. 01)mmHg (F=5. 69, P<0. 05), ankle brachial index from (0. 32 ±0. 23) to (0. 91 ± 0. 16) (F=6. 71, P<0. 05), the volume of blood flow index from the photoelectric (0. 22 ± 0. 04) to (0. 83 ± 0. 13 (F=5. 69, P<0. 05), oxygen saturation from (42. 41 ±9. 61)％ to (79. 61 ±20. 34)％ (F=5. 74, P<0. 05), and DSA score (0. 23 ± 0. 03) increased to (1. 35 ± 0. 23) (F=7. 14, P<0. 05), which was sig-nificantly higher than group B and group C ( F=7. 01, F=7. 04, F=7. 12, F=7. 08, F=7. 15, P<0. 05) for one year after treatment. Conclusions Treatment of peripheral blood stem cells CD34 + cell transplantation combined with oral sarpogrelate hydrochloride can significantly improve the vascular regener-ation and its blood supply in TAO lower extremity limb.

Objective To explore the expression of(hyopxia inducible factor-α,HIF-1α)and gax genes on the intimal hyperplasia for venous autografts in rat.Methods Sixteen Wistar rats were randomLy divided into 2 groups,a control group and an experimental group,8 rats in each group.A rat model of venous autografts was established by transplanting the right external jugulars vein into right common carotid artery in 16rats.The transplanted vein in the experimental group was immersed in solution with recombinant adeno-associated virus(rAAV)and HIF-1α by incubation for 45 minutes at 0℃-4℃ before anastomosis and coated using glue gel in which rAAV-gax added just after anastomosis,the control ones were immersed only in the physiological solution in which rAAV solution without HIF-1α gene added,nothing to be coated except for glue gel only.The vein grafts were taken at 14 days after operation,RT-PCR technique,Western blotting and electric microscopy were used to detect the expression of HIF-1α mRNA and protein,gax mRNA and protein,phenotypic switch of VSMC.Results The expression of HIF-1α mRNA,the experimental group(93.1±22.9)bP,the con trol group(42.7±15.9)bP,P<0.01;the exprossion of gax mRNA,the experimental group(106.9±38.7)bP,the contrd group(50.7±25.8)bP,P<0.01;the exprossion of HIF-1α protein,the experimental group(10.86±2.76)kD,the control group(4.52±1.90)kD,P<0.01;the expression of gax protein,the experimental group(13.65±3.35)kD,the control group(5.40±2.26)kD,P<0.01;VSMC proliferation,the experinental group(21.3±5.4)%,the control group(41.2±8.6)%,P<0.05.Conclusion The present study demonstrated that HIF-1α and gax genes transfection could inhibit proliferation of VSMC and their phenotypic conversion from contractile phenotype to synthetic phenotype in venous autografts.

Objective To investigate the efficiency of autologous transplantation of peripheral blood stem cell for treatment of patients with chronic lower limb ischemia. Methods Forty-six patients with chronic lower limb ischemia were treated by autologous peripheral blood stem cell transplantation. Results Fortytwo patients had pain relief on legs, and cold and cool feelings in lower limbs disappeared. Thirty-five patients had pain relief on feet, and 29 of them had disappearance of cold and cool feelings. Due to necrosis in middle and lower part of leg, 4 patients took extremity amputation after 4 weeks of the transplantation. In the 42 patients who kept their legs 3 months after transplantation, the distance of anginacruris extended from (87. 45 ±41.22) m to (348.52 ± 147.24) m, skin temperature increased from(28.52 ±0.51 ) ℃ to(33.56±0.62) ℃ ,and ankle-brachial index (ABI) increased from(0.48 ±0.06)to(0.75 ±0.07). There were statistical differences, and the scores of the distance of anginacruris, skin temperature, and ABI after transplantation were better than before. six months after transplantation autobiography of lower extremity was used, and neonatal lateral vessels of different degrees were found in 37 patients. Conclusion Autologous transplantation of peripheral blood stem cell is a simple, safe, and effective method, especially in treating patients with lower limb ischemia in which no arterial reconstruction is feasible.

Objective To discuss and evaluate the value of insertion of inferior vena cava filter in treating lower extremity deep venous thrombosis(DVT).Methods Inferior vena cava filters were placed in 46 patients with lower extremity DVT prior treatment,20 in which were treated by therapy with anticoagulation and thrombolysis,and therapy with pressure gradient,and the other 26 patients by operation and thrombolysis therapy,and therapy with pressure gradient.Whether patients occurred pulmonary embolism was observed and the form and site of filters were monitored by periodic fluoroscopy.Results Inferior vena cava filters were placed successfully in all patients,38 cases were implanted permanence inferior vena cava filter,8 cases were implanted temporary inferior vena cava filter.Symptoms and signs of DVT disappeared or remitted in 44/46 patients after treatment.None of pulmonary embolism was occurred.Follow up 2-24 months(average 13 months) for 36 cases with permanence inferior vena cava filter,there was no complication of the filter and pulmonary embolism occurred.Conclusions The method of inserting inferior vena cava filter is simple and safe,which can prevent pulmonary embolism effectually to offer sufficient safeguard for the treatment of DVT.