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Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objectives: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children., Methods: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed., Results: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm ( P <0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments ( P =0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure., Conclusions: Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.

Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp - positive and Hp - negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and β diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T- test, Rank sum test or χ 2 test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp - negative group, the Hp - positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z= 2.00, P= 0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z= -2.24, P= 0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z= -2.10, P =0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z= -2.01, P =0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp - positive group (LDA=4.89, P= 0.045), while Streptococcus and Fusobacterium significantly enriched in Hp - negative group (LDA=3.28, 3.11; P =0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp - positive group were significantly higher than that in Hp-negative group (all P <0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P <0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.

Objective: To explore the incidence and the risk factors of post-polypectomy bleeding and polyp recurrence after colonoscopic high-frequency electrocoagulation snare polypectomy. Methods: Clinical data of 1 826 children who underwent colonoscopic high-frequency electrocoagulation snare polypectomy in the Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2020 was retrospectively analyzed. Demographic characteristics, endoscopic manifestations, pathological features, diagnosis, occurrence of post-polypectomy bleeding and polyp recurrence were collected. The associated risk factors were analyzed by Logistic regression. Results: A total of 1 826 children (1 191 males and 635 females) with 1 967 polypectomies were included. The age was 4.6 (3.2, 6.4) years at initial diagnosis. According to the initial colonoscopy, 1 611 children (88.2%) had solitary polyps, 1 707 children (93.5%) had pedicled polyps, 1 151 children (63.0%) had polyps involving the rectum, and 1 757 children (96.2%) had hamartomatous polyps. Polyposis syndromes were diagnosed in 73 children (4.0%). The post-polypectomy bleeding occurrence was 3.8% (75/1 967). Polyps recurred in 88 children (4.8%). Girls ( OR =2.01, 95% CI 1.26-3.23) and sessile polyps ( OR =2.28, 95% CI 1.15-4.49) were risk factors for post-polypectomy bleeding (both P< 0.05). Multiple polyps ( OR =17.49, 95% CI 9.82-31.18), right-colon involvement ( OR =3.44, 95% CI 1.89-6.26) and non-hamartoma ( OR =2.51, 95% CI 1.04-6.07) were risk factors for polyp recurrence (all P< 0.05). Conclusions: Colonoscopic high-frequency electrocoagulation snare polypectomy has low incidence of post-polypectomy bleeding and polyp recurrence. Female patients and sessile polyps have higher risk for post-polypectomy bleeding. Multiple polyps, right-colon involvement and non-hamartoma polyps increase the risk for polyp recurrence.

Background: The aim of this study was to compare nasogastric (NG) feeding with nasojejunal (NJ) feeding when treating pediatric patients with acute pancreatitis (AP)., Methods: We performed a single-center, prospective, randomized, active-controlled trial involving 77 pediatric patients with AP from April 2014 to December 2017. The patients were randomized into two groups: the NG tube feeding group (34 patients) and the NJ tube feeding group (33 patients). The primary outcome measures included the enteral nutrition intolerance, the length of tube feeding time, the recurrent pain of pancreatitis and complications., Results: A total of 62 patients with AP (31 patients for each group) came into the final analysis. No differences were found in baseline characteristics, pediatric AP score and computed tomography severity score between the two groups. Three (9.7%) patients in the NG group and one (3.2%) patient in the NJ group developed intolerance (relative risk = 3.00, 95% confidence interval 0.33-27.29, P = 0.612). The tube feeding time and length of hospital stay of the NG group were significantly shorter than those of the NJ group (P = 0.016 and 0.027, respectively). No patient died in the trial. No significant differences were found in recurrent pain, complications, nutrition delivery efficacy, and side effects between the two groups., Conclusions: NG tube feeding appears to be effective and safe for acute pediatric pancreatitis compared with NJ tube feeding. In addition, high qualified, large sample sized, randomized controlled trials in pediatric population are needed., (© 2021. Children's Hospital, Zhejiang University School of Medicine.)

Objective: To investigate the differences of gastric mucosa microbiota between children with chronic gastritis and duodenal ulcer under the condition of Helicobacter pylori (Hp) infection. Methods: This prospective cohort study involved 57 children with Hp infection diagnosed by gastric endoscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to "abdominal pain, abdominal distension and vomiting" between January 2018 to August 2018. According to gastroscopy and pathological examination, the children were divided into chronic gastritis group and duodenal ulcer group. Gastric mucosa from Hp infected patients were sampled, and the flora DNA was analyzed by high-throughput sequencing. The statistical difference of α diversity, β diversity between two groups were analyzed. The relative abundance of the two groups in each taxonomic level was analyzed statistically. T test, Rank sum test or χ 2 test was used for comparison between the two groups. Results: A total of 57 children diagnosed with Hp infection were enrolled in this study, including 42 cases of chronic gastritis (the age was (9.3±2.8) years, 22 males and 20 females) and 15 cases of duodenal ulcer (the age was (11.1±3.3) years, 9 males and 6 females). Alpha diversity index Chao and ACE in Hp infected chronic gastritis group were significantly higher than those in Hp infected duodenal ulcer group (217±50 vs . 183±64, t =2.088, P= 0.009;218±47 vs . 192±76, t =1.566, P= 0.016, respectively). The Beta-diversity index such as nonmetric multidimensional scaling (NMDS) analysis were significantly different in the two groups (analysis of similarity R =0.304, P =0.028). Among the main bacteria genera, there were 6 genera with significant differences between the two groups, which were Prevotella (0.190% (0.008%-1.983%) vs. 0.021% (0.005%-2.398%), Z= -2.537, P= 0.011), Alloprevotella (0.097% (0.010%-0.813%) vs. 0.015% (0.003%-0.576%), Z= -2.492, P= 0.013), Haemophilus (0.109% (0.004%-0.985%) vs. 0.014% (0.004%-0.356%), Z= -2.900, P= 0.004), Neisseria (0.074% (0.004%-0.999%) vs. 0.024% (0.003%-0.255%), Z= -2.718, P= 0.007), Streptococcus (0.166% (0.008%-1.869%) vs. 0.045% (0.006%-0.879%), Z= -2.537, P= 0.010), and an unclassified- Microbacteriaceae (0.214% (0.060%-1.762%) vs . 0.117% (0.010%-0.954%), Z= -2.120, P= 0.034). Linear discriminant analysis (LDA) effect sized analysis showed that at the genus level, only Prevotella was significantly enriched in the duodenal ulcer group (LDA=2.90, P =0.010), while Streptococcus, Neisseria and Haemophilus were significantly enriched in the chronic gastritis group (LDA=2.83, 2.82, 2.69, P =0.011, 0.007, 0.004, respectively). Conclusions: The gastric mucosal microbiota in duodenal ulcer associated with Hp is significantly different from that in chronic gastritis. Hp may promote the occurrence of peptic ulcer together with gastric microbiota.

Objective: To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity., Methods: The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry., Results: The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05)., Conclusions: Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.

Objective: To evaluate the effectiveness of enteral nutrition in children with accidental upper gastrointestinal injury. Methods: The medical records of 128 patients with mechanical or chemical gastrointestinal mucosal injury, who were hospitalized in Department of Gastroenterology, Children's Hospital of Zhejiang University School of Medicine from January 1, 2011 to December 30, 2017, were collected. All cases were treated with enteral nutrition. The clinical features and etiologies were retrospectively analyzed. Weight-for-age Z score and lab findings including white blood cells, C-reactive protein, neutrophils, albumin, prealbumin, urea nitrogen and hemoglobin before and after treatment were extracted. The clinical characteristics, the duration of enteral nutrition and gastrointestinal mucosal healing between different etiologies were further analyzed. Normal distribution variables and categorized variables were compared with t test and χ(2) test respectively, and abnormal distribution data was compared with Wilcoxon test. Results: Among all the cases, 77 were males and 51 were females. The average age was (29±22) months. The mean duration of hospitalization and enteral nutrition were (11±7)d and (27±20)d respectively. Vomiting was the most common clinical presentation (72 cases, 56.3%). In 79 cases the problems were caused by mechanical injury, among which coins were most commonly seen. The rest 49 cases were caused by chemical injury. However, the duration of hospitalization ((13±8) d vs. (10±6)d, t= -3.089, P= 0.002) and enteral nutrition ((39±22) vs. (19±14) d, t= -5.365, P= 0.000) were longer in children with chemical injury than those with mechanical injury. A total of 112 cases got complete blood count and C-reactive protein both before and after enteral nutrition. Inflammatory markers, including leukocytes ((7.7±2.7) ×10(9)/L vs. (13.7±5.0) ×10(9)/L, t= 12.244, P <0.05), neutrophils ((3.4±1.9)×10(9)/L vs. (9.4±4.6) ×10(9)/L, t= 13.655, P< 0.05), and C-reactive proteins (5.0(3.0,7.8) vs. 13.5(6.0,40.5) mg/L, Z= 7.776, P <0.05) were significantly decreased. The nutritional markers, including the weight-for-age z score (-0.1 ± 1.0 vs. 0.0 ± 1.0, t= -2.622, P= 0.010) and the prealbumin (0.1 ± 0.1 vs. 0.2 ± 0.0 g/L, t= -3.671, P= 0.001) were significantly increased. Fifty-five (82.1%) children in mechanical injury group recovered in 4 weeks, while 27 (79.4%) children in chemical injury group recovered in 7 weeks. Conclusion: Enteral nutrition can provide adequate nutritional requirements for children with upper gastrointestinal injury, and may help to decrease imflammation and improve mucosal healing.

A boy aged 14 years had abdominal pain as the major manifestation, with elevated serum amylase and lipase. Abdominal ultrasound performed early after onset in another hospital showed enlargement of the pancreas and a reduction in echo. Magnetic resonance cholangiopancreatography (MRCP) showed pancreatic duct dilation and an unclear image of the head of the pancreas. Acute pancreatitis was considered. However, his symptoms were not relieved after fasting, fluid infusion, anti-acid therapy, and somatostatin therapy. Then, abdominal CT scan and MRCP found multiple low-density lesions of the pancreas and enlargement of the hilar and retroperitoneal lymph nodes. Exploratory laparotomy found pancreatic edema and multiple hilar nodules with unclear boundaries, and pathological biopsy showed anaplastic large-cell lymphoma. Since the liver, the spleen, bone marrow, and the central nervous system were not involved, he was diagnosed with stage III primary pancreatic lymphoma. After vindesine and dexamethasone were used to reduce tumor load, the patient underwent vindesine-pirarubicin-asparaginase-dexamethasone chemotherapy once and vinorelbine-dexamethasone chemotherapy 8 times. Imaging examination still showed multiple low-density lesions of the pancreas and retroperitoneal lymph node enlargement. His parents discontinued treatment. It is concluded that the rare causes of acute pancreatitis with poor response to conventional treatment should be considered, especially for patients with abdominal lymph node enlargement. Extranodal lymphoma should be considered, and lymph node biopsy should be performed as early as possible to confirm diagnosis. The prognosis of pancreatic lymphoma is associated with clinical stage and pathology.

Background: The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA., Methods: Twenty-eight patients with BA were divided into three groups according to their age (< 2 months, 2-3 months, and ≥ 3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients preoperatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1., Results: The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged ≥ 3 months were significantly higher than those in patients aged < 2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expression levels in the liver tissue of patients with BA., Conclusions: The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient's age into consideration.

Objective: To explore the clinical features and complications of foreign bodies in the upper gastrointestinal tract in children and to investigate the effectiveness of endoscopic management. Methods: Data of patients with foreign bodies in upper gastrointestinal tract were collected retrospectively at Endoscopy Center, the Children's Hospital, Zhejiang University School of Medicine, from January 2011 to December 2016. Clinical characteristics, the types of foreign bodies, the location and duration of foreign body impaction were summarized. The risk factors of complications and endoscopic removal failure were analyzed by using Logistic regression analysis. Results: A total of 1 334 patients (825 males and 509 females) were enrolled. The median age was 2.5 years, with a range from 0.25 to 15 years and peak age 1-3 years. Twenty patients had esophageal diseases. The most common foreign body ingested was coin ( n= 964, 72.3%). Foreign bodies were most commonly located in the esophagus ( n= 1 002, 75.1%), especially in the upper esophagus ( n= 857, 85.5%). The duration of foreign body impaction ranged from 3 hours to 5 years. Among 1 334 patients, 252 patients (18.9%) developed complications, including ulcers ( n= 101, 40.0%) and perforations( n= 13, 5.2%). The success rate of endoscopic removal was 96.6% ( n= 1 288). By Logistic regression analysis, sharp foreign body ingestion ( OR =6.893, 95% CI: 4.421-10.746) , esophageal impaction ( OR =5.253, 95% CI: 3.352-8.233) and foreign body impaction longer than 24 hours ( OR =4.336, 95% CI: 3.091-6.082) were risk factors of complications. Sharp foreign body ingestion was the risk factor of endoscopic failure ( OR= 5.372, 95% CI: 2.773-10.406) . Conclusions: Coin is the most common foreign body in upper gastrointestinal tract. Sharp foreign bodies impacted in the esophagus over 24 hours increase the risk of complications. Endoscopic removal of foreign bodies from the upper gastrointestinal tract in children has a high success rate. Sharp foreign body ingestion increases the risk of failure in endoscopic removing.

Objective: To study the clinical features and prognosis of gastrointestinal injury caused by foreign bodies in the upper gastrointestinal tract in children., Methods: A retrospective analysis was performed for the clinical data of 217 children who were diagnosed with foreign bodies in the upper gastrointestinal tract complicated by gastrointestinal injury by gastroscopy from January 2011 to December 2016, including clinical features, gastroscopic findings, complications, and prognosis., Results: Among the 217 children, 114 (52.5%) were aged 1-3 years. The most common foreign body was coin (99/217, 45.6%), followed by hard/sharp-edged food (45/217, 20.7%) and metal (35/217, 16.1%). The most common gastrointestinal mucosal injury was ulceration (43.8%), followed by erosion (33.2%). Compared with other foreign bodies, button cells were significantly more likely to cause esophageal perforation (P<0.01). The esophagus was the most commonly injured organ (207/217, 95.4%). Of all the 217 children, 24 (11.1%) experienced infection. The children with perforation caused by foreign bodies had a significantly higher incidence rate of infection than those with ulceration caused by foreign bodies (P=0.003). Of all the 217 children, 204 (94.0%) underwent successful endoscopic removal of foreign bodies. Among these children, 98 were hospitalized due to severe mucosal injury and were given anti-infective therapy, antacids, and supportive care including enteral nutrition through a nasogastric tube and/or parenteral nutrition. Of all the children, 10 left the hospital and were lost to follow-up, and all the other children were improved and discharged., Conclusions: Most cases of foreign bodies in the upper gastrointestinal tract occur at 1-3 years of age. Coin, hard/sharp-edged food, and metal are the most common foreign bodies. Button cells are more likely to cause esophageal perforation. The incidence rate of secondary infection increases with the increasing severity of gastrointestinal mucosal injury. Children undergoing endoscopic removal of foreign bodies and enteral nutrition through a nasogastric tube tend to have a good prognosis.

Objective: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease.The current domestic reports of EoE in children is rare.The aim of this study was to analyze the clinical features, the diagnosis and treatment advance of EoE in children by case analysis and literature review. Method: Clinical data of 22 children with EoE from January, 2011 to December, 2015 in Children's Hospital, Zhejiang University School of Medicine were recorded, retrospective analysis was performed on clinical presentation, gastroendoscopy and histopathological examination features and the treatment. Result: (1) Clinical data: EoE can occur at any age in children (5 months to 13 years). The most common clinical manifestations of EoE are vomiting and abdominal pain, 45% (10/22) and 41%(9/22) respectively. (2) Endoscopy and pathological features of esophageal mucosa: 11 cases with coarse mucous membrane (50%), 6 cases with congestion or erosion of esophageal membrane (27%), 5 cases with longitudinal crack (23%), 3 cases with ring uplift (14%), 3 cases with granular uplift (14%), 3 cases with normal mucosa(14%). Histopathologic manifestation is eosinophil infiltration and the eosinophil counts were all more than or equal to 15/HP. (3) Laboratory results: 13 cases had increasing eosinophil counts and eosinophils proportion (62%). (4)Allergy history: among 22 cases, 7 patients had allergy history (32%). (5) Situation of treatment and remission: 16 cases had clinical remission by oral omeprazole; 2 cases had clinical remission by oral Omeprazole and Montelukast sodium; 1 case acquired remission by elimination diet; 1 case acquired remission by elimination diet and oral prednisone. 2 cases dropped out; Only 2 patients received gastroendoscopy re-examination after 3 months and revealed esophageal mucosal histologic complete recovery. Conclusion: The clinical symptoms of EoE in children varies.Esophageal mucosal features of gastroendoscopy examination in children with EoE were longitudinal crack, white exudates or plaques, paper mucosa, ring uplift and granular uplift.Most patients could achieve remission by using proton-pump inhibitors, only few children needed elimination diet and change formula, or even oral glucocorticoids.

Major ozonated autohemotherapy has been shown to promote recovery of upper limb motor function in patients with acute cerebral infarction, but whether major ozonated autohemotherapy affects remote injury remains poorly understood. Here, we assumed that major ozonated autohemotherapy contributes to recovery of clinical function, possibly by reducing remote injury after acute cerebral infarction. Sixty acute cerebral infarction patients aged 30-80 years were equally and randomly allocated to ozone treatment and control groups. Patients in the ozone treatment group received medical treatment and major ozonated autohemotherapy (47 mg/L, 100 mL ozone) for 10 ± 2 days. Patients in the control group received medical treatment only. National Institutes of Health Stroke Scale score, modified Rankin scale score, and reduced degree of fractional anisotropy values of brain magnetic resonance diffusion tensor imaging were remarkably decreased, brain function improved, clinical efficiency significantly increased, and no obvious adverse reactions detected in the ozone treatment group compared with the control group. These findings suggest that major ozonated autohemotherapy promotes recovery of neurological function in acute cerebral infarction patients by reducing remote injury, and additionally, exhibits high safety., Competing Interests: Conflicts of Interest: None declared.

Objective: To explore the efficacy and safety of the application of enteral nutrition (EN) in gastrointestinal disease in children, and to explore the possibility of the implementation of family EN., Method: Retrospective analysis of disease spectrum, EN approach, preparation, speed and time as well as adverse reactions and outcomes in 47 pediatric patients with gastrointestinal disease underwent EN therapy during July 2014 to March 2015. The nutrition indicators before and after EN therapy were compared by paired t-test., Result: A total of 47 patients were selected, 27 male (57%) and 20 female (43%), aged 0.8 (0.3, 4.0) years, 9 with mechanical or chemical damage to the esophagus, 7 with inflammatory bowel disease (including ulcerative colitis and Crohn's disease), 6 with chronic diarrhea, 5 with acute pancreatitis, 3 with acute diarrhea and severe malnutrition, 3 with short bowel syndrome, 3 with improper feeding, 3 with feeding difficulties, 3 with protein losing enteropathy, 2 with post-enterostomy, 2 with enterocolitis, 1 with gastroesophageal reflux, were diagnosed. Of 47 cases, 22 were given oral nutrition, 28 were fed with nasogastric tube and 4 with nasojejunal tube feeding, 2 with percutaneous endoscopic gastrojejunostomy tube feeding for each. In these tube-feeding cases, 20 cases were treated with continuous infusion and 21 cases with intermittent infusion. Eleven cases were fed with amino acid formula; 21 cases took the choice of peptide formulations; 16 cases chose whole protein formula, including six cases who chose 3.3-4.2 kJ/ml higher energy density formula, 10 cases selected common energy density formula including breast milk. Twenty-one cases suffered from different degrees of adverse reactions, including vomiting in 7 cases, abdominal pain and bloating in 3, diarrhea in 12, secondary respiratory infections in 5. Five patients were discharged after giving up of treatment by parents due to poor efficacy on primary disease; 3 cases were transferred to other departments for further treatment; 15 cases were discharged with a feeding tube for family nutrition and specialist out-patient treatment. The rest 24 cases were all improved and discharged. There were significant differences in nutrition indicators before and after EN, weight-for-age Z score (WAZ)(-2.3±1.9 vs. -1.9±1.8, t=4.156, P=0.000), weight-for-height Z score (WHZ)(-1.9±1.7 vs. -1.2±1.5, t=3.714, P=0.001), albumin ((35±9)g/L vs.(39±6) g/L, t=3.017, P=0.005) and prealbumin ((0.11±0.05)g/L vs.(0.18±0.07)g/L, t=5.144, P=0.000)., Conclusion: EN is suitable for a variety of children's digestive diseases, which can improve the nutritional status of the patients and was safe for clinical application. As the implementation of EN is simple and has good compliance, family EN is proven to be feasible.

We investigated the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in the liver tissue of infants with congenital biliary atresia and neonatal hepatitis, as well as the relationship between the expression of the two factors and liver fibrosis. Thirty-six infants who met the cholestasis criteria were classified into congenital biliary atresia and neonatal hepatitis groups. All specimens were stained with hematoxylin and eosin and Masson's trichrome, and the degree of liver fibrosis was assessed. The scope and level of CTGF and TGF-β1 expression in the different specimens was evaluated by immunohistochemistry and observation. Liver fibrosis in the congenital biliary atresia group was more advanced than that in the neonatal hepatitis group, and the difference was significant (P < 0.01). In the neonatal hepatitis patients, CTGF and TGF-β1 were mainly expressed in the hepatocytes, while they were expressed in both hepatocytes and biliary epithelial cells in the congenital biliary atresia patients, and in these patients the expression was significantly stronger than in the neonatal hepatitis patients (P < 0.01). With the aggravation of hepatic fibrosis, CTGF and TGF-β1 expression levels in liver tissue gradually increased, and their expression levels were significantly correlated (P < 0.01). Liver fibrosis is present in both congenital biliary atresia and neonatal hepatitis patients. The gradual increase of CTGF and TGF-β1 expression levels in liver tissue is associated with liver fibrosis. Early expression of CTGF and TGF-β1 in biliary epithelial cells may be involved in the pathogenesis of congenital biliary atresia.

Endomorphin-2 (EM2) and Substance P (SP) exert suppressive and facilitative influences upon nociception, respectively. Although EM2 and SP were often co-expressed in single neurons in dorsal root ganglion (DRG), it is still unknown if and how the nociception-suppressive influences of EM2 might be exerted upon nociception-facilitative effects of SP in the DRG neurons. We examined these issues in the inflammatory pain model rats produced by subcutaneous injection of the complete Freund's adjuvant into the hind paw. The paw withdrawal threshold for mechanical allodynia was measured. Changes of EM2 and SP release were estimated by measuring intrathecal levels of EM2 and SP through in vivo microdialysis analysis of cerebrospinal fluid. The mechanical allodynia was dose-dependently attenuated by intrathecal injection of EM2 or a neurokinin-1 receptor antagonist, and facilitated by intrathecal injection of SP or a mu-opioid receptor (MOR) antagonist. Importantly, intrathecal level of SP was found to be lowered by intrathecal injection of EM2. Morphologically, colocalization of EM2-, MOR- and SP-immunoreactivity in single DRG neurons was observed by immunofluorescent histochemistry, and co-expression of EM2 and SP in large, dense-cored presynaptic vesicles in primary afferents, as well as localization of MOR on pre- and postsynaptic membrane in spinal dorsal horn, was also confirmed electron miscroscopically. Thus, the results indicated that analgesic influences of EM2 upon inflammatory pain might be exerted through suppression of SP release, supporting the assumptions that binding of EM2 to presynaptic MOR might induce such effects., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is characterized by the degeneration of basal forebrain cholinergic neurons, whose survival and function are affected by neurotrophins and their receptors. The impaired signaling pathway of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) is considered to play an important role in AD pathogenesis. To explore the association of polymorphisms within the NTRK2 gene (encoding TrkB) and sporadic AD (sAD), a case-control study was conducted in a Chinese Han cohort including 216 sAD patients and 244 control participants. Five single nucleotide polymorphisms (SNPs), with four of them within the promoter region and one in intron, were selected and genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR) method. No association was revealed between these SNPs or the haplotypes containing four promoter SNPs and the risk of sAD. The results of this study indicate that polymorphisms in the selected regions of the NTRK2 gene are unlikely to confer the susceptibility of sAD in the Chinese Han population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the feasibility and effectiveness of placement of nasojejunal feeding tube and nasojejunal nutrition feeding in children with acute pancreatitis., Method: Twenty-two patients (of whom 13 had severe acute pancreatitis and 9 acute mild pancreatitis) who needed nutritional intervention were selected. They were from Department of Gastroenterology and Surgery during the years 2009 - 2012, and they were at high nutritional risk after STONGkid nutrition risk screening. The average age of them was 5 - 15 years (9.1 years ± 2.8 years). Assisted by endoscopy, the nasojejunal feeding tube was placed in 22 of 24 patients (in 2 cases of recurrent pancreatitis the tubes were placed again after extubation). Besides the use of regular fasting, antacids, inhibitors of trypsin secretion, and anti-infective treatment, 23 cases of all children got nasojejunal nutrition treatment as well. The outcome measures included the success rate, complications of endoscope-assisted nasojejunal tube placement. The children's tolerance and nutrition indicators (weight, blood lymphocytes count, erythrocytes count, serum albumin, serum creatinine, blood urea nitrogen) were observed before and after enteral nutrition therapy., Result: Malnutrition evaluation was done 24 times before treatment among 22 patients, incidence of malnutrition was 33% in 22 cases. Placement of nasojejunal tube placement was attempted for a total of 24 times and was successful on first placement in 22 cases, in two cases the placement was successful on the second placement, so the success rate of the first attempt for placement was 92%. No significant complications were observed in any of the cases. Twenty-three of 24 cases were given standardized enteral nutrition (one case was not given enteral nutrition therapy but underwent ERCP due to obstructive jaundice). Twenty-two of 23 cases could tolerate enteral nutrition well, only 1 case was unable to tolerate enteral nutrition due to the pancreas schizophrenia, paralytic ileus. The treatment of jejunal feeding success rate was 96%. The feeding duration was 2 - 74 d (27.0 d ± 18.3 d). The adverse reactions include plugging of the tube in two cases, constipation in two cases, five cases had abdominal pain, diarrhea in 2 cases, vomiting in 2 cases and 1 case of jejunum retention. No case had nasopharynx ulcers, gastrointestinal perforation, gastrointestinal bleeding, re-feeding syndrome and infection etc. Blood erythrocytes count, serum creatinine, blood urea nitrogen were not significantly changed. Twenty of 23 cases were cured, 2 cases were improved and 1 case was unchanged., Conclusion: Endoscope-assisted nasojejunal tube placement for children with acute pancreatitis is safe and feasible. Nasojejunal nutrition therapy is effective for acute pancreatitis patients who are at severe nutritional risk, especially for the improvement of the nutritional status of children.

Objective: To assess the value of multiplex PCR-denaturing high-performance liquid chromatography (PCR-DHPLC) method for screening large duplications or deletions in patients with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA)., Methods: DNA was extracted from peripheral venous blood samples from 35 DMD and 6 SMA patients. Large duplications or deletions were screened with multiplex PCR coupled with DHPLC method. The results were validated with testing of positive and negative controls., Results: Known duplications or deletions in all controls were reliably detected with multiple PCR coupled with DHPLC. Large duplications or deletions were found in 71.4% of 35 DMD patients, which included 5 large duplications and 20 large deletions. For SMA patients, deletions of SMN1 exon 7 were detected in 16 samples., Conclusion: Multiplex PCR coupled with DHPLC method is an effective and reliable method for detecting large genomic duplications or deletions in patients with DMD or SMA.

Objective: To evaluate the effect of radiofrequency of different temperatures and durations on sciatic nerve motor conduction velocity (MCV)., Methods: The bilateral sciatic nerve of 70 adult SD rats was dissected and exposed to radiofrequency ablation of different temperatures (30, 50, 55, 60, and 70 degrees C) and durations. The nerves were also exposed to increasing ablation temperatures from 30 degrees C to 50 degrees C with an increment of 5 degrees C (60 s at each temperature), and the changes in the MCV parameters were observed., Results: The MCV parameters of rat sciatic nerve underwent significant changes following the radiofrequency exposures (P<0.05) except for the exposure at 55 degrees celsius; for 10 s. Below the temperature of 55 degrees celsius;, the MCV showed no obvious correlation to the exposure time for the group. For the nerves exposed to radiofrequency of 55 degrees celsius;, the latency was not correlated to the exposure time within 30 s, and data could be obtained from 55 s group; with these exceptions, the latency was found to positively while the negative phase wave inversely correlated to the exposure time. With fixed exposure time of 60 s, the MCV parameters were positively correlated to the ablation temperature (below 50 degrees C). Failure of MCV measurement occurred following exposures to 55 degrees celsius; for 50 s (or longer) or to 60 degrees C (or higher) for 10 s., Conclusion: Low-temperature radiofrequency (below 50 degrees C) produces definite effects on the MCV of rat sciatic nerve, and the effects are not associated with the exposure time, the mechanism of which remains unclear. At a given temperature, the ablation for sufficiently long durations can result in complete block of the MCV. At higher temperatures, radiofrequency exposure cause obvious nerve conduction block.

Objective: To evaluate the effect of chemical lumbar sympathectomy (CLS) on relieving refractory pain in the lower limbs., Methods: Twenty-four patients with refractory pain in the lower limbs underwent CLS under X-ray guidance, and 2 ml contrast agent was injected at 1/3 of the second L2 vertebrae (the L2 sympathetic ganglion). Lidocaine was then injected followed by injection of 7% phenol for performing CLS. The visual analog scale was used to assess the pain severity before and after CLS. The effect of CLS on relieving lower limb pain was compared with that of oral pain-relieving medication., Results: The lower limb pain was obviously relieved as shown by significantly decreased VAS scores in these patients after CLS. CLS exhibited a much more potent effect of pain relief in the lower limbs than the oral medication., Conclusion: CLS produces significant analgesic effects to relieve refractory pain in the lower limbs.

Objective: To study the effect of botulinum toxin type A (BTXA) on spontaneous discharge and sympathetic- sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats., Methods: In chronically compressed rat DRG, spontaneous activities of the single fibers from DRG neurons were recorded and their changes observed after BTAX application on the damaged DGR. Sympathetic modulation of the spontaneous discharge from the compressed DRG neurons was observed by electric stimulation of the lumbar sympathetic trunk, and the changes in this effect were evaluated after intravenous BTXA injection in the rats., Results: Active spontaneous discharges were recorded in the injured DRG neurons, and 47 injured DRG neurons responded to Ca2+-free artificial cerebrospinal fluid but not to BTXA treatment. Sixty-four percent of the neurons in the injured DRG responded to sympathetic stimulation, and this response was blocked by intravenously injection of BTXA., Conclusion: BTXA does not affect spontaneous activities of injured DRG neurons, but blocks sympathetic-sensory coupling in these neurons.

Objective: Our previous work suggested that sensitivity of hippocampal neurons is changed in process of epileptic activities, and closely parallel to the dynamic characteristic of epileptic activity of the neurons. This study investigated the sensitivity of epileptic brain to vagal nerve stimulation (VNS) in epileptic process., Methods: Epileptic model was evoked by penicillin. Left vagal nerves were stimulated to inhibit the seizures induced by penicillin. The electrocorticography (ECoG) and electromyography (EMG) were recorded to analyze inhibiting effect of VNS in epileptic process., Results: It was found that VNS could inhibit the seizures caused by penicillin, and the inhibiting effect of VNS to seizures increased as the vagal nerve stimulating time prolonged. It was also found that the inhibiting effect of VNS to seizures decreased in epileptic process., Conclusion: The results suggested that the sensitivity of epileptic brain to VNS was different in epileptic process. The inhibiting effect of VNS to seizure decreased as the development of seizures.

Objective: To investigate the relationship between noncardiac chest pain (NCCP) and gastroesophageal reflux (GER) in children and to assess the diagnostic value of esophageal pH monitoring in patients with NCCP., Methods: Ambulatory 24 h esophageal pH monitoring was performed in 36 NCCP cases (patient group) with recurrent chest pain and without respiratory diseases and musculoskeletal abnormalities in chest, and 20 of them underwent gastric endoscopy. Eleven of the 20 cases were found to have esophagitis (esophagitis group), while the other 9 cases showed no signs of esophagitis (non-esophagitis group) according to the diagnostic criteria of esophagitis., Results: The episode of esophageal pH < 4, the number of reflux longer than 5 min, the longest reflux time, the percent time of pH < 4 and Boix-Ochoa score in the patient group were 60 +/- 7, 2.44 +/- 0.74, (12.4 +/- 2.8) min, 6.72 +/- 1.39, 24.6 +/- 3.9, respectively, as compared to 33 +/- 4, 0.35 +/- 0.11, (4.3 +/- 0.9) min, 1.25 +/- 0.19, 7.7 +/- 0.9 in the control group. The difference between the two groups had reached significance (t = 3.44, 2.79, 2.73, 3.89, 4.24, respectively, all P < 0.01). The positive rate of acid reflux in the patient group was 58.3% (21/36) whose Boix-Ochoa score higher than 11.99. Eleven of the 20 cases (55.0%) receiving endoscopy were found to have esophagitis, among them the positive rate of GER occurred 81.8% (9/11). Whereas, the other 9 cases (45.0%, 9/20) showed non-esophagitis and the positive rate of GER showed 33.3% (3/9). The number of reflux longer than 5 min and the percent time of pH < 4 in the esophagitis group were 5.8 +/- 2.0, 12.5 +/- 3.5, respectively, as compared to 0.9 +/- 0.5, 3.4 +/- 1.4 in the non-esophagitis group. Significant difference were observed between the two groups (Z = -2.400, -2.545, respectively, all P < 0.05). The episode of esophageal pH < 4, the longest reflux time, and Boix-Ochoa score in the esophagitis group were 73 +/- 11, (26.4 +/- 7.3) min, 41 +/- 10, respectively, as compared to 34 +/- 11, (4 +/- 3) min, 14 +/- 5 in the non-esophagitis group. The difference between the two groups showed significance (Z = -2.926, -2.675, -2.584, respectively, all P < 0.01)., Conclusions: GER is very common in children with NCCP. Esophageal pH monitoring has a therapeutic predictive value in addition to its diagnostic merit for NCCP in children.