Background Pesticides like organophosphorus and pyrethroids are extensively utilized, and associated potential human health risks arising from multi-route exposure, including environmental sources and dietary intake, cannot be overlooked. Conducting human exposure studies using pesticide exposure biomarkers is essential for an objective evaluation of human pesticide exposure levels. Objective To develop a rapid and precise liquid chromatography-tandem mass spectrometry method for the detection of 12 pesticide metabolites in urine, including 5 metabolites of organophosphorus pesticide, 4 metabolites of pyrethroid pesticide, 2 metabolites of herbicides, and 1 metabolite of insecticide. Methods After overnight enzymatic hydrolysis, urine samples were subjected to extraction and purification using Oasis HLB 96-well solid-phase extraction. Subsequently, the samples were analyzed by liquid chromatography-tandem mass spectrometry and quantified using the isotope internal standard method. The developed method was employed to analyze 143 urine samples from a general population to assess its effectiveness and to evaluate pesticide exposure levels. Results All 12 target compounds exhibited good linear ranges, with their correlation coefficients of calibration curves exceeding 0.999. The limits of detection (LOD) ranged from 0.02 to 0.19 μg·L⁻¹, while the limits of quantitation (LOQ) ranged from 0.06 to 0.27 μg·L⁻¹. The recoveries at three spiked levels ranged from 84% to 112%, and the inter- and intra- day precisions of targeted analystes were 0.43%-9.6% and 1.6%-9.7% respectively. Using this method, 143 urine samples from residents in Jiangsu region were analyzed, and 11 pesticides were detected except N,N-diethyl-m-toluamide (DEET). Conclusion The established method of solid-phase extraction combined with liquid chromatography-tandem mass spectrometry has the characteristics of low detection limit, good repeatability, and high throughput, which is suitable for quantitative detection of selected 12 pesticides in large batches of human urine samples, and provides technical support for pesticide internal exposure monitoring and health risk assessment.

Objective To explore the flow chart and key points of etiological differential diagnosis of character"卜"sign in fetal three-vessel and trachea(3VT)view.Methods A retrospective study was performed on ultrasound images of 37 fetuses,who had"卜"sign in 3VT view during fetal heart ultrasound scanning in The Affiliated Suzhou Hospital of Nanjing Medical University from Aug.2020 to Oct.2023.The types of diseases with"卜"sign and the flow chart and key points of differential diagnosis were summarized.All cases were diagnosed by 2 experienced senior prenatal ultrasound doctors independently.Results The incidence of"卜"sign was 0.14％(37/27 019).Among the 37 fetuses with"卜"sign on 3VT view,13(35.14％)cases had complete transposition of great arteries(TGA),11(29.73％)had double outlet of right ventricle with abnormal relationship of great arteries(DORV/AA),7(18.92％)had truncus arteriosus(TA,van Praagh A1,A2 and A3),and 6(16.22％)had pulmonary atresia with ventricular septal defect(PA/VSD).During the process of differential diagnosis,the presence or absence of aorta and pulmonary arteries,the ventricle-artery connection relationship,and the blood supply to both lungs should be focused on,and the final diagnosis can be derived step by step according to the flow chart.The key points of differential diagnosis were as follows:the ventricle-artery connection was inconsistent in TGA;in DORV/AA both aorta and pulmonary artery were entirely or mostly from right ventricle without normal spiral relationship;in TA only a common artery trunk was detected,and main pulmonary artery or its branches were from the artery trunk;and in PANSD pulmonary artery was atresia and only aorta was detected,and the blood supply to both lungs was from ductus arteriosus and/or aortopulmonary collateral arteries.Conclusion The fetal differential diseases with"卜"sign in 3VT view include TGA,DORV/AA,TA(van Praagh A1,A2 and A3),and PA/VSD.Understanding the flow chart and key points of differential diagnosis can improve the prenatal detection rate and diagnosis of related malformations.

Objective:To explore the pathogenesis and prognostic factors of brain metastasis of hepatocellular carcinoma(HCC)after liver transplantation(LT).Methods:Retrospective review was performed for 17 HCC cases with brain metastasis after liver transplantation from 2000 to 2020.All cases were diagnosed as hepatitis B cirrhosis complicated with HCC.All of them were beyond the Milan Criteria.The immunosuppressive regimen consisted of baliximab + mycophenolate mofetil + calcineurin inhibitors(CNIs)+ corticosteroids in early postoperative period with a gradual tapering of corticosteroids and mycophenolate mofetil.Three patients received sirolimus immunotherapy after tumor recurrence and withdrew CNIs.One of three cases received sorafenib.Results:Other organ involvements included lung metastasis( n=16, 94.1%), bone metastasis( n=5, 29.4%)and liver metastasis( n=6, 35.3%). The median survival time after brain metastasis was 7 months and the 1-year cumulative survival rate 29.4%.The median survival time post-LT was 14 months and the 1-year cumulative survival rate 64.7%.Among 7 patients with a resection of brain metastasis, two deaths at Month 1 post-operation were due to cerebral hemorrhage.The longest survival time was 214 months and the median survival time 9 months. Conclusions:The prognosis of brain metastasis post-LT remains poor.However, early detection and reasonable treatment can prolong patient survival time and even achieve long-term survival.Most brain metastases are accompanied by lung metastases.And the finding of lung metastatic tumor hints at a presence of intracranial lesions.

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
China ; Humans ; Liver Transplantation

Objective To preliminary evaluate the mid-term clinical effect of endovascular repair in treating spontaneous extracranial internal carotid artery (ICA) dissection,and to observe the patency of stent.Methods The clinical data and imaging materials of 6 patients with spontaneous extracranial ICA dissection,who were treated with endovascular repair during the period from March 2012 to December 2012,were retrospectively analyzed.The U.S.National Institute of Heahh Stroke Scale (NIHSS) scores were determined before and after endovascular repair,and the postoperative stent patency condition was assessed,the results were analyzed.Results A total of 6 patients,including 4 males and 2 females with a median age of 50 years old (40.75-54.75 years old),received endovascular repair therapy.The median interval from the onset of disease to accept endovascular treatment was 10 days (one week-3 months).After the implantation of stent,the blood flow in the true lumen returned to normal immediately,although part of the false lumen was still filled with contrast agent.Embolism of retinal artery occurred in one patient during the operation,no death occurred.The median follow-up time was 54.4 months (49.7-57.9 months).The NIHSS score determined at the last follow-up visit was not significantly different from the preoperative one (P=0.102).Imaging reexamination revealed that the false lumen at the ICA stent segment disappeared in all 6 patients,and no obvious in-stent stenotic changes were observed.Conclusion Endovascular therapy of selected symptomatic extracranial carotid artery dissection with bare stents can effectively prevent the recurrence of clinical symptoms and promote ICA remodeling with excellent mid-term patency.

Objective To evaluate the indications and results of liver transplantation ior benign liver tumors.Methods From Jan 2001 to Dec 2014,16 patients of inoperable severely symptomatic benign liver tumors underwent liver transplantation in our department.There were 10 cases of polycystic liver disease,2 cases of hepatic epithelioid hemangioendothelioma,1 case of hepatic cavernous hemangioma,1case of liver mesenchymal hamartoma,1 case of hilar bile duct mucinous cystadenoma,1 case of hepatic adenoma.Results 3 cases were dead in the perioperative period.The remaining patients were alive and discharged with normal perioperative liver and kidney function.One case of polycystic liver lost to follow-up,the remaining 12 patients were all alive at the end of a follow-up of 17 to 161 months,with fully active life style.Conclusions Liver transplantation is an effective and sometimes the only treatment option for unresectable and symptomatic benign liver lesion.

Objective To assess the effects of the risk factors of grafts from donors after cardiac death (DCD) on the prognosis of liver transplantation (LT).Methods In this retrospectively study,215 cases of LT using DCD donor grafts were performed at our institution from September 2013 to January 2017.Due to the loss to follow-up in 4 cases,211 cases were enrolled in the study.The following DCD donor data were collected:gender,age,primary disease,ABO blood type,body mass index (BMI),medical history (fatty liver,hypertension),ICU hospitalization time,mechanical ventilation time,warm ischemia time,cold ischemia time,and indexes of routine laboratory test before donation.Statistical analyses using the Kaplan-Meier method,log-rank test,multivariate step-wise Cox regression were performed.Results Of the 211 donors,univariate analysis showed that the overall 6-month,1-,and 3-year survival rate after DCD LT was 88％,84％,and 82％,respectively.Univariate analysis showed that donor serum sodium level ＜136 mmol/L (P =0.018) and cold ischemia time ＞9 h (P =0.013) were all significant risk factors affecting overall survival after DCD LT.Additionally,donor BMI ＞30 kg/m2 (P =0.011) and donor age ＞60 years (P =0.025) were significantly associated with postoperative complications.Multivariate analysis showed that donor serum sodium level (P=0.025) was an independent risk factor of survival after DCD LT.Conclusion To select suitable DCD liver allografts and control risk factors of donor can help to improve outcomes of recipients.

Objective To establish and evaluate the animal model induced by inhalation injury of airborne fine particulate matter (PM2?5). Methods We manufactured equipment for rats aerosol inhalation with PM2?5. The effects of several facters such as concentrations(100 ± 10 μg/m3、150 ± 10 μg/m3、200 ± 10 μg/m3 )、time(1w、2w、4w、8w、12w)、method (non?exposed intratracheal instillation method and aerosol inhalation) and animals (Wistar rats, BN rats and guinea pigs) were investigated to establish the model. The respiratory rate, forced vital capacity ratio of forced expiratory volume ( FEV1/FVC) and arterial partial pressure of oxygen ( PO2 ) were measured, the pathological changes of bronchial and lung tissues under light microscope were observed. The success animal model was builded as the pneumonia was observed from the pathological changes of lung tissue. Results The Wistar rats exposed to PM2?5 aerosol inhalation for 8 weeks, we can see that the weight growth rate of rat decreased, WBC count and mononuclear cells count increased, the macrophages ratio decreased in BALF, the respiratory rate of lung increased while arterial PO2 and FEV1/FVC decreased, inflammation and pulmonary fibrosis changes were observed by bronch and pulmonary pathology, inflammatory changes with a dose?response relationship were observed. Exposed to PM2?5 aerosol inhalation for different time(1 w、2 w、4 w、8 w、12 w)with same dose, the score issue lesions of lung and bronchus in Wistar rats increased and the 8w group is obvious. The Wistar rats exposed to PM2?5 with different method ( aerosol inhalation and non?exposed intratracheal instillation method) for 8w, the aerosol inhalation worked as effectively as perfusion while mortality rate of aerosol inhalation is lower. Different animals ( Wistar rats, BN rats and guinea pigs) exposed to PM2?5 aerosol inhalation for 8w, the same results were observed with three method respectively while mortality rate of Wistar rats lower. Conclusions The optional conditions that the Wistar rats were continuously inhaled for 8w PM2?5 with a dose of 150 ± 10 μg/m3 were established. The animal model could be used on a national scale, especially in Fujian province. The results would be useful for the development of the research of the prevention and countermeasures of PM2?5 pollution.

Objective To investigate the effects of bone marrow-derived stem cells (BMMSC)on the expressions of inflammatory cytokines and Toll-like receptor (TLR)4 pathway in primary hepatic stellate cells (HSC)with direct and indirect contact coculture system.Methods Purified HSC were separately treated with LPS in the concentrations of 0,50,100 and 150 g/L for 48 h.Proliferation ratio was tested with cell counting kit-8 to determine the optimal concentration.HSC in LPS were divided into three groups,including HSC alone group,cocultured with BMMSC at 1∶1 group and cocultured with transwell group at the optimal concentration.The supernatants were collected to detect the concentrations of interleukin-6 (IL-6)and tumor necrosis factor (TNF)-α.Cells were further divided into seven groups, including BMMSC without LPS group,HSC without LPS group,BMMSC with LPS group,HSC with LPS group,BMMSC in transwell system group,HSC in transwell system group,all cells in transwell system group and direct contact system group.The mRNA expressions ofα-smooth muscle actin (α-SMA) and collagen I were detected by quantitative real-time PCR,and protein expressions of TLR4,myeloid differentiation factor 88 (MyD88)and nuclear factor-κB (NF-κB)were analyzed by Western blot.Data were analyzed with one-way ANOVA analysis.Results The proliferation rate of HSC in 50,100 and 150μg/L LPS were (129.77±11 .26)%,(162.90±13.15 )% and (55 .12 ±11 .6)%,respectively compared with HSC without LPS group.The differences were statistically significant (t =5 .91 ,10.70 and 8.65 , respectively,all P <0.05).The concentrations of IL-6 and TNF-αin HSC alone group,directly/indirectly cocultured group were (252.02 ±30.94)ng/L and (148.00 ± 10.27 )ng/L,(88.52 ±6.61 )g/L and (72.63±5 .54)ng/L,(103.74±7.14)ng/L and (81 .79 ±6.92 )ng/L,respectively.The differences between HSC alone group and directly/indirectly cocultured group were significant (t=12.66 and 15 .82, 11 .81 and 12.34,respectively,all P < 0.05 ).The directly and indirectly cocultured groups were significantly different (t=3.83 and 2.53,respectively,both P <0.05 ).The mRNA expressions of α-SMA and collagen I in HSC with LPS were remarkably increased compared with HSC without LPS (t =14.16 and 11 .84,respectively,both P <0.05 )and reversed by cocultured with BMMSC (t =11 .98 and 4.47,respectively,P <0.05).All cells in transwell group expressed moreα-SMA and collagen I than the direct contact group (t=3.70 and 3.19,respectively,P <0.05 ).The TLR pathway associated protein expressions,TLR4,MyD88,and NF-κB in HSC in transwell group were significantly down-regulated compared with HSC with LPS group.And all cells in transwell system had higher level of protein expressions compared with direct contact system (P < 0.05 ).Conclusions BMMSC are effective in inhibiting HSC activation and inflammatory cytokines excretion,which may be modulated through TLR4 pathway and cell to cell contact.

Objective To evaluate the feasibility and outcome of liver transplantation in the treatment of liver metastatic cancer. Methods Four patients with pathologically confirmed liver metastatic cancer underwent liver transplantation, including one of liver metastases from pancreatic endocrine tumor, one from rectal endocrine tumor, one from stomach stromal tumor and one from colorectal carcinoma. Classic surgical method was adopted, i.e. orthotopic liver transplantation for the recipients and transplants came from cadaveric donors. Results All the four patients had a smooth operation, an uneventful early postoperative recovery and good living quality. The patient with liver metastases from pancreatic endocrine tumor had liver tumor recurrence at four and a half years after the transplantation, and then underwent left lateral hepatic lobectomy, without any recurrence until now. The patient with liver metastases from rectal endocrine tumor had right renal and pelvic tumor metastasis at 16 months after the operation, and died of tumor recurrence 5 years after the liver transplantation. The patient with liver metastases from gastric stromal tumor had extensive pelvic metastases at five and a half months after the transplantation, and survived with tumor for 4 years and 6 months after the operation. The patient with liver metastases from colorectal carcinoma had extensive bilateral lung metastases at 3 months after the transplantation and died one and a half years after the operation. Conclusion For well?differentiated unresectable metastatic liver cancers, liver transplantation may serve as a treatment option and better treatment results can be achieved for some highly selected patients.