[Endoscopic diagnosis and treatment of early colorectal cancer and precancerous lesions: current status and future prospects].

Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.

[Preliminary application of the Asia-Pacific colorectal screening score combined with the quantitative fecal occult blood in colorectal neoplasia screening].

To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.

[The optimal thresholds of the quantitative fecal immunochemical test for opportunistic screening of colorectal neoplasia].

Objective: To investigate the significance of quantitative fecal immunochemical test (FIT) for opportunistic screening of colorectal neoplasia, and to propose the most optimal thresholds to improve the screening level of early colorectal neoplasia. Methods: The opportunistic screening participants were recruited from the Department of Gastroenterology & GI Endoscopy Center of the Seventh Medical Center of PLA General Hospital, and stool sample was collected before colonoscopy and the quantitative FIT was analyzed by OC-MICRO analysator for each patient. We assessed test performance in detecting colorectal neoplasia (advanced adenoma and CRC)with different thresholds on sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1 448 objects were enrolled in this study, including 714 male (49.3%)and 734 female (50.7%).All participants were classified according to the result of colonoscopy and pathology, and 242 cases of colorectal neoplasia were found, containing 157 advanced adnoma and 85 colorectal cancer. The FIT threshold increased from 50 µg/L to 200 µg/L, while the positivity rate dropped from 11.5% to 8.6% and the sensitivity in detecting colorectal neoplasia dropped from 47.9% to 38.8%. However, the specificity increased from 96.8% to 98.2% and the positive predictive value increased from 82.3% to 87.0%.The miss rate of colorectal cancer increased from 11.8% (n=10) to 17.6% (n=15) along with the increase in FIT thresholds, but the miss rate of 100 µg/L and 150 µg/L was the same as 12.9% (n=11). Conclusions: Quantitative FIT,which is simple and fast,with the threshold of 100 µg/L for opportunistic screening, has a high sensitivity and specificity for the diagnosis of colorectal neoplasia,and is an important index in screening and diagnosis of colorectal neoplasia.

Immunological function and antibacterial activity of two ferritin proteins from the freshwater pearl mussel Hyriopsis schlegelii.

Ferritin is a conserved iron-binding protein involved in host defense and cellular iron metabolism in most organisms. We investigated the expression profiles of two ferritin genes (designated HsFer-1 and HsFer-2) in the hemocytes, gonad, and hepatopancreas of Hyriopsis schlegelii, when challenged with bacteria and metal ions. HsFer gene transcription increased 1.8-7.7- and 1.9-6.1-fold in these tissues after stimulation with Staphylococcus aureus and Vibrio anguillarum, respectively. In addition, following exposure to Fe3+, expression of HsFer-1 and HsFer-2 was elevated by 1.5-6.1- and 3.6-10.1-fold, respectively. Levels of HsFer-1 and -2 mRNA also increased significantly after treatment with Cu2+ and Pb2+ at certain concentrations. Moreover, recombinant HsFer-1 and -2 were able to inhibit the growth of two strains of bacteria, and the former efficiently chelated Fe3+. From these results, we conclude that HsFer-1 and -2 may be involved in iron metabolism and immune defense by inhibiting the growth of bacteria.

[Jinghuaweikang capsules combined with furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori infection: a multicenter randomized controlled clinical trial].

Objective: To explore the efficacy of Jinhuaweikang capsules plus furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori (H.pylori) infection. Methods: This is a prospective randomized controlled multicenter clinical trial. Patients with chronic gastritis from H. pylori infection in whom eradication treatment failed were recruited from 6 hospitals. All patients were divided into 4 groups using stratified randomization: group A1 (PAFJ), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ Jinghuaweikang 3 capsules, twice a day for 10 d (d1-10); group A2, PAFJ therapy as in group A1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28); group B1 (PAFB), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ bismuth potassium citrate 220 mg, twice a day for 10 d (d1-10); group B2, PAFB therapy as in group B1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28). At least 28 days after the end of treatment, all patients underwent 13C urea breath test for assessment of H. pylori eradication. Results: A total of 357 patients, 145 males and 212 females, were recruited, including 90 in group A1, 88 in group A2, 89 in group B1, and 90 in group B2. The eradication rates of H. pylori in groups A1 and A2 were 76.1%(67/88)and 79.6%(70/88) in per-protocol (PP) analysis, 74.4%(67/90) and 79.6%(70/88)in intention-to-treat (ITT) analysis; the rates in groups B1 and B2 were as 85.9%(73/85) and 92.1%(81/88) in PP analysis, 82.0%(73/89) and 90.0%(81/90)in ITT analysis. There were statistically significant differences in PP eradication rates among the 4 groups (P=0.020); there was statistically significant difference between groups A1 and B2, and also between groups A2 and B2 (P=0.003, 0.020), but not between groups A1/A2 and B1 (P>0.05), nor between groups B1 and B2 (P>0.05). No statistically significant differences in ITT eradication rates were found among the 4 groups (P>0.05). The improvement of belching and poor appetite for patients in groups A2 and B2 was better than those in groups A1 and B1. Conclusions: The efficacy of Jinghuaweikang capsules plus furazolidone-based quadruple therapy is superior to combination with furazolidone-based triple therapy as the rescue treatment of H. pylori, and superior to bismuth-containing quadruple therapy. Extending administration of Jinghuaweikang capsules to 28 days may better improve symptoms of indigestion.

Complete mitochondrial genome of a natural triploid crucian carp mutant, Carassius auratus var. pingxiangnensis, and phylogenetic analysis of different ploidies in crucian carp.

Carassius auratus var. pingxiangnensis is a natural triploid crucian carp mutant. In order to understand its placement and genetic background at the gene level, the characteristics of mitochondrial DNA sequences and phylogenetic relationship were examined. The results showed that the mitochondrial DNA is a circular double-stranded DNA molecule that is 16,576 bp in length with 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a non-coding control region. Mitochondrial genes overlapped by a total of 40 bp in 11 different locations from 1 to 14 bp. The base composition of the C. auratus mitogenome was estimated to be 29.70% A, 26.74% C, 15.35% G, and 28.21% T. The central conserved blocks and the conserved blocks were compared and were similar among C. auratus var. pingxiangnensis and six other cyprinids with different ploidies. The origin of light strand replication was similar to that of other vertebrates; it was 33 bp, but the characteristic sequence motif 5ꞌ-GCCGG-3ꞌ at the base of the stem within tRNA(Cys) was mutated to 5ꞌ-GGCGG- 3ꞌ. Our phylogenetic analysis based on whole mitogenome sequences indicated that C. auratus var. pingxiangnensis was clustered with C. auratus and then sister-grouped with Carassius gibelio. The systemic developmental tree of crucian carp with different chromosome ploidies showed that diploid C. auratus auratus was clustered with triploid C. auratus auratus, sister-grouped with tetraploid C. auratus auratus, and clustered with other diploid, triploid, and tetraploid C. auratus.

Symptomatic diffuse esophageal spasm as a major ictal manifestation of post-traumatic epilepsy: a case report.

Post-traumatic epilepsy (PTE) can create diagnostic confusion when typical epileptic seizures are not manifest. Abdominal symptoms as a manifestation of PTE are rare in this setting. We present a 43-year-old female with paroxysmal chest and abdominal pain, nausea, salivation, and intermittent dysphagia. Esophageal testing demonstrated diffuse esophageal spasm, but smooth muscle relaxants provided no relief. Finally, after history revealed that a motor vehicle accident temporally preceded symptom onset, video electroencephalography confirmed PTE. Therapy with anti-epileptic drug completely resolved symptoms, and the esophageal motor pattern normalized. We speculate that abnormal epileptiform discharges from the seizure focus altered cerebral input to intrinsic esophageal innervation, resulting in inhibitory dysfunction and a picture resembling diffuse esophageal spasm. This is the first report of symptomatic esophageal spasm as a major ictal manifestation of PTE.

Expression pattern of the zona pellucida 3 (ZP3) gene during ovarian development and the location of ZP3 protein in oocytes in a natural, wild triploid crucian carp mutant, Carassius auratus var. Pingxiangnensis.

Carassius auratus var. Pingxiangnensis (designated CaP), distributed in the Pingxiang region of Jiangxi Province, China, is a natural, wild triploid crucian carp mutant that has two reproductive development modes: gynogenesis and bisexual reproduction. Little information is available about the expression pattern of the zona pellucida 3 (ZP3) gene during ovarian development and the location of the ZP3 protein in oocytes of this fish. In this study, we obtained the full-length cDNA of ZP3 (CaP_ZP3). CaP_ZP3 contains an open reading frame of 1305 bp that encodes 435 amino acid residues. Real-time polymerase chain reaction (PCR) was used to determine the CaP_ZP3 mRNA expression levels in the ovary at different stages of maturation. Results revealed high levels of CaP_ZP3 expression in 4- to 8-month-old ovaries (stage II-stage III), with a significant decline in 9- to 12-month-old ovaries (stages IV-stage V). The high levels of CaP_ ZP3 transcripts during the early growth period suggest an important role for CaP_ZP3 in early oocyte development. In addition, a polyclonal antibody was prepared against CaP_ZP3, and the immunofluorescence localization was determined. CaP_ZP3 protein was detected close to the oocyte plasma membrane. The results also showed that no fluorescent signal was detected in stage I and II oocytes. CaP_ZP3 protein is primarily detected in stage III oocytes, and the protein accumulates as oocytes develop into stage IV oocytes. These results suggested that the transcription and translation of the CaP_ZP3 gene is asynchronous and that the transcription of the CaP_ZP3 protein occurs prior to its translation in this triploid fish.

Molecular characteristics and expression of calmodulin cDNA from the freshwater pearl mussel, Hyriopsis schlegelii.

Calmodulin (CaM) is a multifunctional intracellular calcium ion receptor protein that participates in a range of cellular processes, including calcium metabolism in mussels. To investigate the role of CaM in freshwater mollusk shell calcium metabolism, the full-length CaM cDNA was isolated from the freshwater pearl mussel, Hyriopsis schlegelii (referred to as hsCaM) using SMART RACE technology. The full-length hsCaM was 855 bp in size, containing a 70-bp 5'-untranslated sequence, a 447-bp open reading frame, a 309-bp 3'-untranslated sequence, and a 26-nucleotide long poly(A) tail. The hsCaM mRNA expression in different mussel tissues was examined using real-time PCR. The hsCaM mRNA was found to be ubiquitously expressed, but far more abundant in the gill, foot, and mantle than in the posterior adductor muscle. Real-time PCR was also used to determine hsCaM mRNA expression levels in mantle tissues of H. schlegelii at different ages. No significant differences between one-, two-, and three-year-old mussels were detected, but expression increased in four-year-old mussels and then decreased in five-year-old mussels. CaM appears to be involved in calcium regulation of the mantle in four-year-old mussels, which may secrete more mother of pearl during pearl culture.

Mismatch repair gene mutations in Chinese HNPCC patients.

To explore the characteristics of DNA mismatch repair gene mutations in Chinese patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome, the MLH1 and MSH2 genes from probands of 76 HNPCC families were sequenced. By doing so, two frame-shift mutations, three splice-site mutations and fourteen missense mutations (thirteen missense mutations and one nonsense mutation) were identified in the MLH1 gene. In addition, one splice-site mutation and six missense mutations were detected in the MSH2 gene. None of these mutations were detected in 100 matched healthy controls. The remaining mutation-negative cases were subjected to large fragment deletion analysis using multiplex ligation-dependent probe amplification (MLPA). By doing so, five large fragment deletions were detected in the MSH2 gene. No large fragment deletions were detected in the MLH1 gene. We conclude that the MLH1 and MSH2 genes in Chinese HNPCC families exhibit broad mutation spectra.

MicroRNA-185 regulates chemotherapeutic sensitivity in gastric cancer by targeting apoptosis repressor with caspase recruitment domain.

Gastric cancer remains the second leading cause of cancer deaths worldwide. Resistance to chemotherapy is a significant barrier for effective cancer treatment. Here, we identified miR-185 to be a contributor to chemosensitivity in gastric cancer. We observed low levels of miR-185 in gastric cancer cell lines and clinical tissues, compared with gastric epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-185 increased the sensitivity of gastric cancer cells to low-dose chemotherapeutic agents, which alone cannot trigger significant apoptosis. Conversely, knockdown of endogenous miR-185 prevented high-dose chemotherapy-induced apoptosis. In elucidating the molecular mechanism by which miR-185 participated in the regulation of chemosensitivity in gastric cancer, we discovered that apoptosis repressor with caspase recruitment domain (ARC) is a direct target of miR-185. The role of miR-185 was confirmed in gastric tumor xenograft model. The growth of established tumors was suppressed by a combination therapy using enforced miR-185 expression and a low dose of anticancer drugs. Finally, we found that RUNX3 (Runt-related transcription factor) was involved in the activation of miR-185 at the transcriptional level. Taken together, our results reveal that RUNX3, miR-185 and ARC regulate the sensitivity of gastric cancer cells to chemotherapy.

High-resolution anorectal manometry in newborns: normative values and diagnostic utility in Hirschsprung disease.

BACKGROUND: Conventional methods of screening for Hirschsprung disease (HD) in newborns (barium enema, BE; anorectal manometry, ARM; rectal suction biopsy, RSB) have limitations and/or are invasive. High-resolution anorectal manometry (HR-ARM) is a minimally invasive technique that has potential to overcome most of these limitations, but normative data and performance characteristics have not been reported in newborns. The aims of our study were to assess anorectal sphincter metrics including resting pressure (RP), anal canal length (ACL), and rectoanal inhibitory reflex (RAIR) in healthy and asymptomatic newborns, and to explore the role of HR-ARM in the diagnosis of HD using these normal parameters. METHODS: All procedures were performed using solid state HR-ARM equipment (Medical Measurement Systems, Enchede, The Netherland) by a single operator. In the first phase, 180 asymptomatic newborns (term newborns 95, preterm newborns 85) were studied, and anal RP, ACL, and RAIR were measured. In the second phase, 16 newborns with clinical manifestations of HD were studied (9 of whom had histopathologic confirmation), and parameters compared to asymptomatic newborns. KEY RESULTS: Normative RP values were higher in term newborns compared with preterm newborns (p < 0.05), and correlated with age. Progressive maturation of the anal sphincter was evident with chronologic age, both in preterm and term newborns. RAIR was present in all normal subjects. Using absent RAIR as indicative of HD, HR-ARM had a sensitivity 89% and specificity of 83% compared to RSB; these performance characteristics were better than BE (sensitivity 78%, specificity 17%), with significantly higher diagnostic accuracy (80% vs 53%, respectively, p = 0.009). CONCLUSIONS & INFERENCES: Anorectal sphincter pressure progressively matures with incremental increase in RP during the first months of life. HR-ARM is an effective and safe method that complements the diagnosis of HD in newborns.