Clinical significance of expression of leptin in patients with biliary atresia and hepatic fibrosis / 中华肝胆外科杂志

Objective:To study the relationship and the role of leptin in children with biliary atresia and hepatic fibrosis to provide a treatment basis for these patients.Methods:The clinical data of children with biliary atresia or congenital biliary dilatation (CBD) who underwent surgical treatment at the Department of General Surgery of Tianjin Children's Hospital from August 2019 to August 2021 were retrospectively analyzed. Of 31 children included in this study, there were 14 males and 17 females, with age of 60 (30, 63) d. Children with biliary atresia served as the study group ( n=26) and children with CBD served as the control group ( n=5). Leptin protein, α-smooth muscleactin (α-SMA) and phosphorylation of extracellular-regulated protein kinase 1/2 (p-ERK1/2) in liver tissues were detectd by immunohistochemistry (IHC). The expression level of leptin mRNA in liver tissues were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results:The average optical density values of leptin protein, α-SMA protein and p-ERK1/2 protein in the liver tissues of children in the study group were significantly higher than the control group ( P<0.05). The expression levels of leptin, α-SMA and p-ERK1/2 in liver tissues of children with biliary atresia significantly increased with increase in fibrosis degree ( P<0.05). The expression level of leptin in liver tissues of children with biliary atresia was positively correlated with the liver fibrosis grade ( rs=0.876), α-SMA ( r=0.723) and p-ERK1/2 ( r=0.725) ( P<0.01). The results of qRT-PCR showed that the content of leptin mRNA in liver tissues of children with biliary atresia was significantly higher than that of children with CBD ( P<0.05). Conclusion:Expressions of leptin increased with aggravation of degrees of hepatic fibrosis in biliary atresia. Leptin may be involved in activation of HSCs through the ERK1/2 signaling pathway in the process of hepatic fibrosis due to biliary atresia.

Research advances on the relationship between age at Kasai portoenterostomy and prognosis for biliary atresia / 中华肝胆外科杂志

Kasai portoenterostomy is the preferred treatment for biliary atresia. Age at Kasai portoenterostomy is an important factor affecting the prognosis of children with biliary atresia and avoiding liver transplantation. Choosing the appropriate surgical age, restoring good bile drainage, improving the native liver survival rate, and avoiding early liver transplantation are the items that clinicians have always been working on. The age at Kasai portoenterostomy was correlated with the jaundice clearance rate, native liver survival rate, and the incidence of postoperative cholangitis. This article systematically reviewed the research advances on the relationship between age at Kasai portoenterostomy and prognosis for biliary atresia, aiming to provide the basis for the ideal surgical age of Kasai.

Analysis of diagnostic value of biliary atresia / 中华肝胆外科杂志

Biliary atresia is a disease characterized by progressive inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, which is an important cause of persistent jaundice in infants, Without timely treatment, it can develop rapidly into cirrhosis, and the child will die of liver failure. Therefore, the early diagnosis of biliary atresia is particularly important. The diagnosis of biliary atresia mainly depends on intraoperative cholangiography and liver biopsy, but they have the disadvantages including invasion, complex operation and many complications, which is not conducive to the early diagnosis of biliary atresia. In comparison, some non-invasive examination methods such as laboratory examination and imaging examination have obvious advantages. In this paper, the value of various diagnostic methods of biliary atresia is analyzed, which provides new ideas for its early diagnosis.

The diagnostic value of GGT combined with ultrasound found gallbladder abnormality in infants with biliary atresia / 中华普通外科杂志

Objective To evaluate GGT in combination with B ultrasound for the diagnosis of biliary atresia (BA) infants suffering from obstructive jaundice.Methods A retrospective analysis was made on 69 sick infants including 55 BAs and 14 non-BAs as identified by intraoperative cholangiography.The preoperative laboratory GGT and ultrasound data were collected and analyzed.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were compared.Results BA patients had significantly higher GGT than Non-BA patients (t =-4.164,P ＜ 0.05).The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of GGT ＞ 306 U/L were 69.1％,92.9％,97.4％,43.3％,73.9％,respectively.In BA group,abnormal gallbladder was significantly associated with proadening portal vein,broadening hepatic artery compared with Non-BA patients (x2 =9.995,P ＜0.05).The accuracy of abnormal gallbladder on ultrasound was 78.3％.When two method combined for the diagnosis of BA,the sensitivity,specificity,positive predictive value,negative predictive value were 92.7％,92.9％,98.1％ and 76.5％ and accuracy can reach 92.8％.Conclusions For obstructive jaundice infants with GGT ＞ 306 U/L and abdominal gallbladder ultrasound finding intraoperative cholangiography should be carried out to make definite diagnosis of BA.

The expression and significance of integrinαvβ8, p38 and ERK1/2 in the liver of children with biliary atresia / 天津医药

Objective To investigate the expression and significance of integrin αvβ8, p38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) proteins, which are TGF-β1 pathway related regulatory protein, in liver fibrosis of children with biliary atresia (BA). Methods Fifteen cases of BA (Kasai group) and 10 cases of congenital biliary dilatation (CBD group) were collected in Tianjin Children’s Hospital. And liver biopsy specimens were collected in Tianjin first central hospital, including 10 cases of BA children who underwent liver transplantation due to liver failure after Kasai operation (liver transplantation group). The specimens of front part of the right lobe of the liver were taken for HE and immunohistochemistry (IHC) staining. The expressions ofαvβ8, p38 and ERK1/2 in liver were observed by IHC staining in three groups of liver tissues. Results HE staining showed fibroblast hyperplasia occasionally in CBD group, portal area expansion, fibrous tissue proliferation and wide spread bridging fibrosis with few pseudo lobules in Kasai group. In transplantation group, portal area was widened, the degree of fibrosis was severe and bridging fibrosis generally formed resulted in pseudo lobules widely. Imunohistochemistry showed that the expressions of αvβ8 and ERK1/2 were weakly positive, and the expression of p38 was negative in CBD group. In Kasai group, the expressions of αvβ8, p38 and ERK1/2 proteins were all strongly positive in liver cytoplasm, biliary epithelial cells and vascular endothelial cell cytoplasm. In liver transplantation group the expressions of αvβ8, p38 and ERK1/2 proteins were all strongly positive. The semi-quantitative analysis showed that the expressions levels of αvβ8, p38 and ERK1/2 were significantly higher in Kasai and liver transplantation groups than those of CBD group (P0.05). Conclusion The expressions ofαvβ8, p38 and ERK1/2 are gradually increased in liver of BA with the process of fibrosis, which indicate that they may be involved in the process of BA liver fibrosis.

The etiology and treatment of cholangitis after Kasai operation in biliary atresia patients / 天津医药

Cholangitis is one of the most common complications after Kasai operation in children with biliary atresia (BA), whose precise etiology is still unclear. The occurrence of cholangitis may be the results of concurrent effects of various factors such as the structural change of intrahepatic bile duct or insufficient volume of bile flow. The diagnosis for cholangitis is based on clinical manifestations nowadays, and combined therapies including antibiotics, steroids and hepatoprotectants have been used empirically. The prophylaxis and treatment of postoperative cholangitis is the key to improve the liver survival of biliary atresai patients. Only by figuring out the etiology of cholangitis that we can prevent it and make sure the long-term survival of BA patients.

The clinical experience of diagnosis and treatment of late vitamin K deficiency intracranial hemorrhage as the first symptom of biliary atresia / 天津医药

Objective To investigate the surgical diagnosis and treatment of late vitamin K deficiency intracranial hemorrhage caused by biliary atresia. Methods Clinical data of six cases of biliary atresia with late vitamin K deficiency intracranial hemorrhage were collected in the Department of Neurosurgery of Tianjin Children’s Hospital from January 2000 to December 2013. Data were analyzed to identify the biliary atresia as soon as possible in the treatment of intracranial hemorrhage and prolonged jaundice in children. Results Six cases (1 male, 5 female), mean age was (16.0±2.6) days, and were treated with external drainage of intracranial hematoma and infusion therapy. In the treatment, children were found jaundice exacerbation and doubted about biliary atresia. After consultation by general surgeons, children were transferred to the department of general surgery for further treatment at an average age of (29.1±1.2) days, and were diagnosed as biliary atresia by intraoperative cholangiography. Conclusion Pediatric neurosurgeon should have a sufficient understanding and make an early diagnosis to late vitamin K deficiency intracranial hemorrhage caused by biliary atresia, to avoid delaying the optimal treatment time of biliary atresia.

Research progress on the survival of autologous liver in children with biliary atresia after Kasai operation / 天津医药

Biliary atresia (BA) is a kind of disease of unknown etiology, characterized by progressive inflammation and fibrosis of obstructive biliary diseases. Kasai portoenterostomy is the only method to treat BA. However, about 80% of the patients treated by Kasai operation still need liver transplantation in the future. Many factors affect the survival of autologous liver in children with BA after Kasai operation, including the types of BA, laparoscopic Kasai surgery or traditional open surgery, patient’s age at surgery, condition of liver function, occurrence of cholangitis, jaundice clearance, using steroids and central hospitalization. This article reviews the factors that affect the survival of autologous liver in patients with BA after Kasai surgery.

The effects of TGF-β1 and Smad2 on liver fibrosis of biliary atresia / 天津医药

Objective To investigate the expression and function of transforming growth factor (TGF)-β1 and Smad2 in liver fibrosis of biliary atresia (BA). Methods Liver biopsy specimens were collected from autopsy (normal group, n=5), congenital biliary dilatation (CBD group, n=10), BA patients underwent Kasai procedure (early hepatic fibrosis group, n=19) and liver transplantation (transplantation group, n=11). The first three groups were collected from January 2010 to July 2014 in Tianjin Children’s Hospital, and the last group was collected from January 2013 to January 2014 in Tianjin First Central Hospital. The hematoxylin and eosin (HE) stain were used to observe the degree of liver fibrosis of four groups. Immunohistochemistry (IHC) was used to observe expressions of TGF-β1 and Smad2 in liver tissues of these samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the quantitative mRNA of TGF-β1 and Smad2 in these samples. Results Results of HE showed that no fibrosis in autopsy group, mild fiber cell hyperplasia in CBD group, severe fibrosis in Kasai group and significant pseudolobule in transplantation group. Results of IHC showed that TGF-β1 was expressed in the cytoplasm of hepatocytes, bile duct cells, lymphocytes and neutrophils. The average optical density of TGF-β1 was the highest in Kasai group compared with that of other three groups (P 0.05). Results of qRT-PCR showed that both TGF-β1 mRNA and Smad2 mRNA were the highest in early hepatic fibrosis group than those of CBD group and transplantation group (P<0.017). Conclusion In early stage of BA, TGF-β1 and Smad2 promote liver fibrosis until the formation of P-P,P-C desmosome structure. However, with BA fibrosis becomes more serious, the pro-fibrogenic function of TGF-β1 and Smad2 becomes less.

Values of histopathological assessment grading score in differential diagnosis of extrahepatic biliary atresia / 临床与实验病理学杂志

Purpose To study the values of liver histopathological assessment grading score in differential diagnosis between biliary atresia ( BA) and infantile hepatitis ( IHS) . Methods Thirty four cases of BA and sixteen cases of IHS were analyzed retrospectively, which were diagnosed by biopsy. A hepatic histopathological assessment grading score was developed. This consisted of eight features such as cholestasis, hepatocellular damage, bile duct proliferation, portal edema, portal inflammation, portal fibrosis, extramedullary hemopoiesis and multinucleated giant hepatocytes. The total scores were 24 points. All the cases were assessed one by one. Results The total scores of BA were significantly higher than that of IHS (P<0. 001). The frequencies of bile duct proliferation, portal fibrosis and portal edema were significantly higher in BA than that in IHS group, while the frequency of multinucleated giant hepatocytes was significantly higher in IHS than that in BA group. Conclusions This scoring system is helpful in differentiating BA from IHS.

MicroRNA and hepatic fibrosis of biliary atresia / 天津医药

Biliary atresia (BA), an inflammatory sclerosing cholangiopathy, is the leading cause of cholestasis in infants. Pathologic features of BA include progressive inflammation and intrahepatic and extrahepatic bile duct fibrosis. BA is charac?terized by rapid liver fibrosis. The activation of hepatic stellate cell (HSC) is most important in liver fibrosis. Many mecha?nisms are involved in this process. miRNA can promote the activation of HSC through a variety of signaling pathways by regu?lating the expression of target gene, then playing a regulatory role in the synthesis and degradation of extracellular matrix (ECM). A lot of literatures show that PI3K/Akt is closely related to the occurrence and development of hepatic fibrosis. PI3K/Akt signaling pathway is involved in the activation of HSC proliferation and apoptosis. MiRNA activates PI 3K/Akt signaling pathway through various target genes, and then activates HSC to promote the development of liver fibrosis. In this paper, the miRNA related to biliary atresia of liver fibrosis is summarized.

The early screening and countermeasures of biliary atresia / 天津医药

It is generally accepted that Kasai operation is the best treatment for biliary atresia (BA). The implementation of early screen plan improves the age threshold at the suitable time point of Kasai operation. This is the key issue to improve the survival rate of autologous liver in biliary atresia. The monitoring of stool color card, B-ultrasonography and serum con?jugated bilirubin can be used for preliminary seeming biliary atresia. It is very important to improve the ability of basic unit medical staff for major improvements to the understanding of the significance of biliary atresia. In some country and district, the local government has put the screen list for BA into healthcare booklet for children. Thus, it has a significant impact of early screen plan on the diagnosis and treatment of BA, and it can improve the BA autologous liver survival time. So far, there is still no BA early screen plan in the nationwide. We should pay attention to BA, and establish early screen system in different local health unit quickly.

Current research in roles of CD38,CD138 and IgG4 in the pathogenesis of biliary atresia / 天津医药

Biliary atresia (BA) is one of the most serious pediatric surgical digestive system diseases with progressive liv?er bile duct inflammation and fibrous obstruction. Currently, the etiology of BA is not clear. It may be associated with genetic predisposition, viral infections and immune injury. Now many scholars believe that it was resulted from multiple factors. Among them, the theory of immune-inflammatory is supported by most scholars. Now the mechanisms of CD38, CD138 and IgG4 in autoimmune liver disease were reported in literature. BA and other autoimmune liver diseases are similar in terms that both inflammatory and immune responses plays irreplaceable role during disease development. Therefore, this article briefly review the role of CD38, CD138 and IgG4 in the inflammation-immunity of BA.

Advances in the research of liver fibrosis in biliary atresia / 天津医药

Biliary atresia (BA) is one of the most serious digestive system diseases, which threatens the health of infants. Liver fibrosis is a major cause of death in children with BA. In the process of the pathogenesis of BA, virus infection can in?duce a series of immune and inflammatory reaction, result in a decrease of regulatory T cells (Treg cells) and high expression of CD14, activating a variety of inflammatory pathways and TGF-β/Smad2/3 pro-fibrogenic pathway, which produces a large number of medium damage of liver cells and bile duct cells, releases proinflammatory factor, oxygen metabolism matter and cytokines. These changes further aggravate damage of hepatobiliary system and cause the internal environment imbalance of liver parenchyma cells. The imbalance of internal environment with adaptive degeneration and necrosis in liver parenchyma cells, hepatic macrophages and gathered inflammatory cells leads to the activation of hepatic stellate cells (HSCs). HSCs can be converted into fibroblast cells, and promote the process of liver fibrosis. Immune and inflammatory lesions, pro-fibrogenic pathway are the important factors in contributing to liver fibrosis and cirrhosis of biliary atresia.

The role of RET proto-oncogene methylation in the pathogenesis of Hirschsprung's disease / 天津医药

Objective To investigate the relationship between the methylation of RET (proto-oncogene, RET) and Hirschsprung disease (HD), and understand its significance in the development of intestinal wall ganglion cells. Methods Twenty-one surgical removal specimens, which were all dilation segment of HD in Tianjin Children’s Hospital, were used as experimental group, and 5 samples of non-HD normal colon tissues were used as control group. The bisulfite sequencing (BSP)-direct detecting method was used to detect RET CpG island methylation status. The expression of RET protein was detected by immunohistochemistry in experimental group and control group. Results In the experimental group 12 cases (57.14%) were found methylation, but no methylation was found in control group. The average optical density of methylated RET protein was 0.201±0.015 in 12 cases. The average optical density of un-methylated RET protein was 0.364±0.023 in 9 cases (P<0.05). Conclusion RET CpG island methylation reduced protein expression levels of RET. The corollary RET gene methylation may influence the expression levels of RET protein, thereby affecting the ganglion cell development, and thus participating in the occurrence of HD.

Clinical Significance of GDNF/GFRα1/RET Expression in Distal Rectum with Congenital Anorectal Malformation / 天津医药

Objective To evaluate the significance and expression of the GDNF/GFRα1/RET genes in distal rectum with Congenital Anorectal Malformations(ARMs) Methods Specimens were collected from resected colon which is 3 cm away to the anus and the distal of rectum in 12 ARMs patients. Haematoxylin and Eosin (HE) staining, immunohistochemical (IHC) staining and reverse transcription PCR (RT-PCR) were used to test RET, GDNF and GFRα1 expression in the differ-ent site of samples with ARMs. Results Expression of ganglia and RET, GDNF and GFRα1 were all negative in distal rec-tum in 12 ARMs patients. Ganglionic cells were found in tissues 3 cm away from the anus where RET, GDNF and GFRα1 expression were also positive in those ARMs patients. Expression of RET, GDNF and GFRα1 were strong positive in middle and low imperforate anus indicated by brown color and week positive in high imperforate anus indicated by yellow color. One case of faeces contamination and one case of loose motion without anal incontinence were found in post-op follow up of high ARMs patients. By contrast, one case of rectal mucosa prolapse and one case of occasional faeces contamination which recov-ered with hip bath were found in post op follow up in middle or low ARMs. Conclusion The unsatisfactory anorectal func-tion is possibly related to the decrease or lost of neurotrophic factors (GDNF/GFRα1/RET) and ganglia in the myenteric plex-uses post plastic surgery in ARMs patients.

Care of neonatal cholestasis:opportunities to improve early diagnosis of biliary atresia / 中华实用儿科临床杂志

The early screening and early diagnosis of biliary atresia is the key to improve the 5-year native liver survival rate,jaundice-free-native-liver survival rate and overall survival rate.So far,the neonatal jaundice,especially that caused by surgical cholestasis exists the lack of awareness.Because of this reason,the delay depletion jaundice patients did not receive early diagnosis and treatment until the severe complications happened.So,it has often missed the best period of operation for the biliary atresia.Called for local medical health governments to formulate the effective early screening methods of biliary atresia and the reasonable schedule of postnatal follow-up,and improving the ability of basic unit medical staff in well understanding cholestasis disease in order to achieve early diagnosis and treatment.Consequently,it will improve the situation of diagnosis and treatment of biliary atresia in our country.

Surgical treatment for infant biliary hypoplasia with huge choledochal cyst / 中华普通外科杂志

Objective To explore diagnosis and treatment of biliary hypoplasia with huge choledochal cyst in infants.Methods From Feb 2003 to Dec 2011,278 choledochal cyst cases were treated in our hospital.There were 3 infant cases of biliary hypoplasia with huge extrahepatic choledochal cyst diagnosed and treated during this period.All patients underwent cholangiogram demonstrating patent,but markedly diminutive extrahepatic biliary structures.After excision of the cyst,hepatic duct was injured in 1 case.The cyst wall was removed,a stent was put inside of hepatic duct,and Roux-en-Y hepaticojejunostomy was porformed.Results All three patients (ages from 1 month to two months) received the Roux-en-Y hepaticojejunostomy,none of our patients has developed stenosis and fistula of the Roux-en-Y hepaticojejunostomy.Intraoperative cholangiogram showed the huge choledochal cyst and diminutive intrahepatic ducts.All three cases were followed-up for 1-5 years,there was no jaundice and nor stones formation.Conclusions In cases of huge choledochal cyst when intraoperative cholangiogram demonstrates a diminutive biliary tree with huge choledochal cyst,great care is required during cyst excision in order not to injury the hepatic duct.Stent placement into hepatic duct helps bile flow at early stage after surgery.

Expression of NOS in the rat colorectal carcinoma cells / 中国普通外科杂志

Objective To study the expression of nitric oxide synthase (NOS) during the development of rat colorectal carcinoma. Methods Rat colon carcinoma was induced by injection of 1,2- dimethylhydrazine (1,2-DMH).The expression of eNOS, nNOS and iNOS in normal colon mucosa and colorectal carcinoma was observed by immunohistochemistry. ResultseNOS and nNOS were expressed in normal mucosa. Neither eNOS nor nNOS alterations were observed in carcinoma tissues,iNOS expression was very strong in carcinoma samples(87%)and only 10% in normal colon mucosa. ConclusionOur results show that iNOS may play an important role in the 1,2-DMH induced colon tumorigenesis.