Peutz-Jeghers syndrome ( PJS ) is a rare autosomal dominant inherited disease characterized by mucocutaneous pigmentation and multiple gastrointestinal polyposis. Recent studies suggested that mutation in STK11 gene on chromosome 19p13. 3 was considered as the major cause of PJS. In this paper,we summarized the clinical features, pathogenesis,diagnosis and treatment of PJS through literature review.

Objective:To evaluate the efficacy and safety of balloon-assisted enteroscopy (BAE) in the follow-up treatment of small intestinal polyps in patients with Peutz-Jeghers syndrome (PJS).Methods:From February 2005 to September 2019, the clinical data of patients with PJS who visited Air Force Medical Center many times and underwent BAE for small intestinal polyps surveillance and treatment were collected. The number of follow-up treatment times under BAE, operation-related complications and conservative theragy or surgical treatment were observed. Spearman rank correlation analysis was used to analyze the correlation between follow-up treatment times under BAE and the number and maximum diameter of small intestinal polyps.Results:A total of 165 PJS patients were enrolled, including 98 males and 67 females, and the mean age of first visit was (22.5±9.4) years. A total of 664 BAE operations were performed in the 165 PJS patients. The number of BAE operations and the number of follow-up treatments for each patient were 4.0±1.8 and 2.8±1.1, respectively. There were 26, 52, 35, 28, 12, 4, 2, 2, 2 and 2 patients who underwent 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 BAE operations, respectively. There were 165, 76, 30, 12, 4 and 4 patients who received 2, 3, 4, 5, 6 and 7 follow-up treatments, respectively. During the first to the fifth times of BAE follow-up treatment, the numbers of small bowel polyps resected under BAE of each patient were 7.0 (2.0, 11.0), 4.0 (2.0, 10.0), 3.0 (1.0, 8.5), 5.5 (1.8 , 10.3) and 3.0 (2.0, 6.8), respectively; and the maximum diameters of resected small intestinal polyps were 4.5 cm(3.0 cm, 6.0 cm), 3.0 cm(1.5 cm, 4.0 cm), 2.0 cm (1.5 cm, 3.0 cm), 3.0 cm(2.5 cm, 4.0 cm) and 2.5 cm(1.5 cm, 4.0) cm, respectively. The results of Spearman rank correlation analysis indicated that the number of follow-up treatment under BAE was negatively correlated with the number and maximum diameter of resected small intestinal polyps ( r s=-0.141, P=0.003; r s=-0.400, P<0.01). The total incidence of operation-related complications of small intestinal polyps resection under BAE was 3.2% (21/664), and 61.9%(13/21)of the complications were cured by conservative therapy. During the follow-up period, there were 26 cases of PJS complicated with intestinal intussusception, of which 20 cases (76.9%, 20/26) disappeared after BAE resection of small intestinal polyps. A total of 13 patients received surgery for intussusception (6 cases) or large polyps blocking the intestinal lumen (7cases). Conclusions:BAE is safe and effective in the follow-up treatment of small intestinal polyps in PJS. It can reduce the number and maximum diameter of small intestinal polyps, prevent and treat the complications related to small intestinal polyps, and effectively reduced surgical treatments.

OBJECTIVETo correlate the clinical characteristics with mutations of the STK11 and FHIT genes in 16 patients with Peutz-Jeghers syndrome (PJS).

METHODSPotential mutations in the coding regions and flanking sequences of the STK11 and FHIT genes were detected with PCR and Sanger sequencing.

RESULTSOf the 16 patients with PJS, 8 had novel mutations in the coding region of the STK11 gene, 1 had a previously reported mutation. 1 carried a mutation in the exon 10 of the FHIT gene, which is a non-coding region. None of the mutations was detected in the immediate family members. None of the patients with STK11 gene mutations had mutation in the FHIT gene. The mutation rate of the STK11 gene among patients with PJS was 56.25%.

CONCLUSIONMutations of the STK11 gene are the major cause of PJS. Few such patients had mutations of the FHIT gene. Mutations of the FHIT gene may play a part in the pathogenesis of PJS.

Acid Anhydride Hydrolases ; genetics ; Adolescent ; Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Neoplasm Proteins ; genetics ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Young Adult

Objective To investigate the effect of different medical standards for the urinary system on the enlistment of pilots between PLAAF and USAF , and offer support to amendment .Methods Data on pilots′final enlistment between 2012 and 2015 were analyzed , and results of physical examinations of the urinary system were compared according to differ -ent medical standards .Results One hundred and twenty teenagers enrolled in this examination were disqualifiied due to defects of the urinary system while 97 applicants were qualified after comprehensive assessment of the urinary system .The main problems with the urinary system that affected results of pilots′enlistment were nephroptosia , renal cyst , microscopic hematuria , renal calcified foci and calculus .Conclusion Medical standards for the urinary system are different between PLAAF and USAF, especially those for nephroptosia , renal cyst and microscopic hematuria .The medical standards directo-ry about the urinary system approved by USAF can serve as a reference during our revision of current medical enlistment standards.

Objective The aim of this study was to investigate how different concentrations of dextran sulfate sodi-um ( DSS) influence the establishment of mouse model of inflammatory bowel disease ( IBD) and the effect of DSS on the expression of colitis-associated immune factors.Methods The DSS solution in different concentrations (3%, 5%, 7%) were given to male C57BL/6J mice to generate mouse inflammatory bowel disease model.The IBD mice were observed by defecation characteristics, body weight, and survival time.The animals were sacrificed at 6 days after the start of DSS drinking.The general appearance of colons was observed and scored.Moreover, the pathological changes of the colon were examined and analyzed by routine histology.The expression of immune factors in the spleen was detected by real-time PCR.Results The mice in the 3%, 5%, 7% DSS groups developed murine colitis.In addition, the incidence of IBD and mouse mortality rate was directly proportional to the increase of DSS concentration.Furthermore, the higher concentra-tion of DSS induced the expression of proinflammatory factors including TNF-α, IFN-γand IL-17A, but cause a decrease of anti-inflammatory factors such as IL-4, IL-10 and Treg-related transcription factor Foxp3.Conclusions Our data suggest that giving 5%DSS solution to C57BL/6J mouse is appropriate to efficiently establish a murine IBD model.This laid an important foundation for further studies of the pathogenesis of IBD, biological characteristics, and intervention factors.

Objective:To evaluate the value of blood urea nitrogen (BUN)/creatinine (Cr) ratio for guiding the access route of double balloon enteroscopy (DBE) for small intestinal bleeding.Methods:The clinical information was collected from 105 patients who underwent DBE for suspected small intestinal bleeding at Air Force Medical Center from January 2015 to October 2019. Patients were divided into the elevated BUN/Cr group ( n=52) and the normal BUN/Cr group ( n=53), with a cut-off value of 81. Comparison was made for the detection rate of lesions between the oral route and anal route separately in the two groups using Chi-square test. Results:Among the 105 patients with suspected small intestinal bleeding, definite causes of bleeding were identified in 79 patients by DBE, and the overall lesion detection rate was 75.24% (79/105). In the elevated BUN/Cr group, the overall lesion detection rate was 76.92% (40/52), among which 79.49% (31/39) was through oral and 47.37% (9/19) through anal enteroscopy. In the normal BUN/Cr group, the overall lesion detection rate was 73.58% (39/53), and 63.64% (21/33) was transoral and 51.43% (18/35) transanal. The lesion detection rate of transoral enteroscopy in the elevated group was significantly higher than that in the normal group ( χ2=6.576, P=0.010). There was no significant difference in the lesion detection rate of transanal enteroscopy between the two groups ( χ2=2.230, P=0.135). Conclusion:For patients with active small intestinal bleeding (active bleeding within 48 hours), the BUN/Cr ratio higher than 81 may indicate that DBE should be performed firstly via oral route.

Objective:To investigate the efficacy of double balloon enteroscopy (DBE) in the treatment of bleeding from small intestinal vascular lesion and risk factors of bleeding recurrence .Methods:From April 2013 to May 2020, at Air Force Medical Center, the clinical data of 65 patients with confirmed or suspected bleeding from small intestinal vascular lesion were retrospectively analyzed. The patients were divided into DBE treatment group (patients of Yano classification 1a and 1b received argon plasma coagulation, and patients of Yano classification 2 and 3 accepted combination of titanium clip and submucosal injection of lauromacrogol sclerosing agent) and non-DBE treatment group (traditional treatments such as stopping anticoagulant or antiplatelet drugs, blood transfusion, and iron supplementation). The bleeding recurrence of patients with single small intestinal vascular lesion between DBE treatment group and non-DBE treatment group, and patients with single or mulitiple vascular lesion of DBE treatment group were compared. Univariate analysis was used to analyze the clinical data of patients with or without recurrent bleeding. Multivariate logistic regression model was used to analyze the independent risk factors and protective factors of recurrent bleeding in small intestinal vascular lesion. Independent sample t test, chi-square test and Fisher exact probability method were used for statistical analysis. Results:Forty-four (25 of single vascular lesion and 19 of multiple vascular lesion) patients were diagnosed with small intestinal vascular lesions and received DBE treatment (DBE treatment group). Twenty-one patients with single vascular lesion accepted traditional treatment (non-DBE treatment group). The recurrent rate of bleeding in patients with single vascular lesion of DBE treatment group was lower than that in patients with single vascular lesion of non-DBE treatment group and patients with multiple vascular lesion of DBE treatment group (24.0%, 6/25 vs. 71.4%, 15/21 and 12/19), and the differences were statistically significant ( χ2=10.348 and 6.848, P=0.001 and 0.009). The results of univariate analysis showed that the proportion of blood transfusion, hypertension, complicated with valvular heart disease and DBE treatment in patients with rebleeding or not rebleeding from small intestinal vascular lesion was different with statistically significant (69.7%(23/33) vs. 37.5%(12/32), 51.5%(17/33) vs. 18.8%(6/32), 42.4%(14/33) vs. 12.5%(4/32) and 54.5%(18/33) vs. 81.2%(26/32), χ2=6.777, 7.628, 7.265, and 5.298, all P<0.05). The results of multivariate logistic regression analysis indicated that blood transfusion during the course of disease (odds ratien ( OR)=3.736, 95% confidence interval ( CI) 1.082 to 12.898, P=0.037) and complication with valvular heart disease ( OR=4.916, 95% CI 1.107 to 21.829, P=0.036) were independent risk factors of bleeding recurrence in patients with small intestinal vascular lesions. DBE treatment was the protective factor of bleeding recurrence in patients with small intestinal vascular lesion ( OR=0.214, 95% CI 0.057 to 0.808, P=0.023). Conclusions:DBE is effective in the treatment of small intestinal vascular lesion bleeding, especially for single vascular lesion. Blood transfusion during disease course and complication with valvular heart disease are independent risk factors for bleeding recurrence in patients with small intestinal vascular lesion.

OBJECTIVE: To screen for pathogenic variants in the coding regions of STK11 gene among Chinese patients with Peutz-Jeghers syndrome (PJS). METHODS: Peripheral blood samples were collected from 64 patients. The coding regions of the STK11 gene were detected by PCR and Sanger sequencing. RESULTS: Fourty-eight patients were found to harbor STK11 gene variants, which included 39 types of variants consisting of missense, nonsense, insertional, deletional and splice site variants. Among 64 PJS patients, the detection rate of point variants was 75.00% (48/64), of which missense variants accounted for 29.17% (14/48), nonsense variants accounted for 29.17%(14/48), insertion variants accounted for 2.08% (1/48), deletional variants accounted for 10.42% (5/48), and splice site variants accounted for 29.17% (14/48). The detection rates of sporadic cases and those with a family history were 71.8% (28/39) and 80.0% (20/25), respectively. Two variants (c.250A>T, c.580G>A) occurred in 3 PJS probands. Thirteen variants were unreported previously and were considered to be pathogenic. CONCLUSION The detection rate of variants among Chinese PJS patients is similar to that of other countries. A number of novel common variant sites were discovered, which enriched the spectrum of PJS-related variants.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Humans ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

Objective:To analyze the relationship between STK11 mutation and the cumulative risk of intussusception in patients with Peutz-Jeghers syndrome (PJS). Methods:From December 2017 to June 2019, the clinical data of 167 patients with PJS in Air Force Medical Center were collected, including gender, age, family history, age of first intussusception and results of gene test. Kaplan-Meier was used to analyze the cumulative risk of intussusception in patients with different mutation types. Wilcoxon rank sum test and log-rank test were used for statistical analysis.Results:Among 167 patients, 89.8% patients (150/167) had S TK11 mutation, and 50.7% of the mutation sites were found in exons 1, exon 4 and exon 5. And 70.6% patients (118/167) developed intussusception. The median age of patients with intussusception for the first time was 15 years (ranged from 2 to 52 years). Among 118 PJS patients with intussusception, 53 patients had family history and 65 patients had no family history; 70 cases were male and 48 cases were female. There were no statistically significant differences in the cumulative risk of intussusception between PJS patients with and without family history, and between male and female PJS patients (both P>0.05). There were 107 cases (90.7%) with STK11 mutation ( STK11 mutation group) and 11 cases (9.3%) without STK11 mutation ( STK11 non-mutation group). The median age of first intussusception of STK11 gene mutation group was younger than that of STK11 non-mutation group, and the difference was statistically significant ( Z=-2.108, P=0.035). In STK11 mutation group, 29 cases (27.1%) were nonsense mutations (nonsense mutation group), 23 cases (21.5%) were frameshift mutations (frameshift mutation group), 21 cases (19.6%) were missense mutations (missense mutation group), 26 cases (24.3%) were splicing mutations (splicing mutation group) and 8 cases (7.5%) of other mutations. There were statistically significant differences in the cumulative risk of intussusception between the STK11 mutation group and the STK11 non-mutation group, the STK11 splicing mutation group and the STK11 non-mutation group, STK11 missense mutation group and the STK11 non-mutation group ( χ2=5.570, 10.167 and 6.653, all P<0.05). There were no statistically significant differences in the cumulative risk of intussusception between STK11 nonsense mutation group and STK11 non-mutation group, between STK11 frame-shift mutation group and STK11 non-mutation group, among groups with different mutation types of STK11 gene (all P>0.05). Conclusions:The younger the age of first intussusception in PJS patients with STK11 mutation, the higher the cumulative risk. The mutation type of STK11 gene has potential value for the risk assessment of intussusception in PJS patients.

Background/Aims: Enteroenteric intussusception in Peutz-Jeghers syndrome (EI-PJS) is traditionally treated by surgery. However, enteroscopic treatment is a minimally invasive approach worth attempting. We aimed to develop a risk scoring system to facilitate decision-making in the treatment of EI-PJS. Methods: This was a single-center case-control study, including 80 patients diagnosed with PJS and coexisting intussusception between January 2015 and January 2021 in Air Force Medical Center. We performed logistic regression analysis to identify independent risk factors and allocated different points to each subcategory of risk factors; the total score of individuals ranged from 0 to 9 points. Then, we constructed a risk stratification system based on the possibility of requiring surgery: 0–3 points for “low-risk,” 4–6 points for “moderate-risk,” and 7–9 points for “high-risk.” Results: Sixty-one patients (76.25%) were successfully treated with enteroscopy. Sixteen patients (20.0%) failed enteroscopic treatment and subsequently underwent surgery, and three patients (3.75%) received surgery directly. Abdominal pain, the diameter of the responsible polyp, and the length of intussusception were independent risk factors for predicting the possibility of requiring surgery. According to the risk scoring system, the incidence rates of surgery were 4.44% in the low-risk tier, 30.43% in the moderate-risk tier, and 83.33% in the high-risk tier. From low- to high-risk tiers, the trend of increasing risk was significant (p<0.001). Conclusions We developed a risk scoring system based on abdominal pain, diameter of the responsible polyps, and length of intussusception. It can preoperatively stratify patients according to the risk of requiring surgery for EI-PJS to facilitate treatment decision-making.