JOM-4S Overhauser Magnetometer and Sensitivity Estimation.

The Overhauser magnetometer is a scalar quantum magnetometer based on the dynamic nuclear polarization (DNP) effect in the Earth's magnetic field. Sensitivity is a key technical specification reflecting the ability of instruments to sense small variations of the Earth's magnetic field and is closely related to the signal-to-noise ratio (SNR) of the free induction decay (FID) signal. In this study, deuterated 15N TEMPONE radical is used in our sensor to obtain high DNP enhancement. The measured SNR of the FID signal is approximately 63/1, and the transverse relaxation time T2 is 2.68 s. The direct measurement method with a single instrument and the synchronous measurement method with two instruments are discussed for sensitivity estimation in time and frequency domains under different electromagnetic interference (EMI) environments and different time periods. For the first time, the correlation coefficient of the magnetic field measured by the two instruments is used to judge the degree of the influence of the environmental noise on the sensitivity estimation. The sensitivity evaluation in the field environment is successfully realized without electrical and magnetic shields. The direct measurement method is susceptible to EMI and cannot work in general electromagnetic environments, except it is sufficiently quiet. The synchronous measurement method has an excellent ability to remove most natural and artificial EMIs and can be used under noisy environments. Direct and synchronous experimental results show that the estimated sensitivity of the JOM-4S magnetometer is approximately 0.01 nT in time domain and approximately 0.01 nT/Hz in frequency domain at a 3 s cycling time. This study provides a low-cost, simple, and effective sensitivity estimation method, which is especially suitable for developers and users to estimate the performance of the instrument.

Keratin 8 Mutations Were Associated With Susceptibility to Chronic Hepatitis B and Related Progression.

BACKGROUND: Keratin 8 and 18 (K8/K18) are the exclusively expressed keratins intermediate filaments pair in hepatocytes that protect against liver injuries and viral infection. We aimed to explore the genetic link between keratin variants and chronic hepatitis B virus (CHB) infection in a large cohort from a high-epidemic area. METHODS: Genomic deoxyribonucleic acid was isolated from patients, and Sanger sequencing was applied to analyze variations in exon regions of K8/18. Biochemical and functional analysis of novel mutations was also performed. RESULTS: The 713 participants comprised 173 healthy controls and 540 patients, which covered chronic hepatitis (n = 174), decompensated cirrhosis (n = 192), and primary liver carcinoma (n = 174). The frequency of mutations in K8/18 was significantly higher among patients than among controls (8.15% vs 0.58%, P < .001). Significant differences were found between the chronic hepatitis subgroup and controls in multiple comparisons (6.32% vs 0.58%, P = .006). All 21 missense mutations (3.89%) were detected in the keratin 8 (K8), including 4 novel conserved missense variants (R469C, R469H, A447V, and K483T). Multivariate logistic regression analysis demonstrated a higher risk of acute-on-chronic liver failure (ACLF) and missense variants (odds ratio = 4.38, P = .035). Transfection of these variants caused keratin network disruption in vivo. CONCLUSIONS: Novel K8 cytoskeleton-disrupting variants predispose toward ACLF in CHB.

Rome Foundation-Asian working team report: Asian functional gastrointestinal disorder symptom clusters.

OBJECTIVE: Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. DESIGN: 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. RESULTS: Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). CONCLUSION: We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings.

Rome foundation Asian working team report: Real world treatment experience of Asian patients with functional bowel disorders.

BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities. METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction. RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use. CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.

Small intestinal bacterial overgrowth as an uncommon cause of false positive lactose hydrogen breath test among patients with diarrhea-predominant irritable bowel syndrome in Asia.

BACKGROUND AND AIM: It has been reported that small intestinal bacterial overgrowth (SIBO) may lead to false positive diagnoses of lactose malabsorption (LM) in irritable bowel syndrome patients. The aim of this study was to determine the influence of SIBO on lactose hydrogen breath test (HBT) results in these patients. METHODS: Diarrhea-predominant irritable bowel syndrome patients with abnormal lactose HBTs ingested a test meal containing (99m) Tc and lactose. The location of the test meal and the breath levels of hydrogen were recorded simultaneously by scintigraphic scanning and lactose HBT, respectively. The increase in hydrogen concentration was not considered to be caused by SIBO if ≥ 10% of (99m) Tc accumulated in the cecal region at the time or before of abnormal lactose HBT. RESULTS: LM was present in 84% (31/37) of irritable bowel syndrome patients. Twenty of these patients agreed to measurement of oro-cecal transit time. Only three patients (15%) with abnormal lactose HBT might have had SIBO. The median oro-cecal transit time between LM and lactose intolerance patients were 75 min and 45 min, respectively (Z=2.545, P=0.011). CONCLUSIONS: Most of irritable bowel syndrome patients with an abnormal lactose HBT had LM. SIBO had little impact on the interpretation of lactose HBTs. The patients with lactose intolerance had faster small intestinal transit than LM patients.

Discrepancies between Nonalcoholic and Metabolic-associated Fatty Liver Disease by Multiple Steatosis Assessment.

Background and Aims: The redefinition of metabolic-associated fatty liver disease (MAFLD) from nonalcoholic fatty liver disease (NAFLD) has caused a revolution in clinical practice, and the characteristics of patients with steatosis but not MAFLD remain unclear. The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steatosis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD. Methods: A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020. Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, controlled attenuation parameter (CAP), and fatty liver index (FLI). Fibrosis was assessed by the NAFLD fibrosis score, transient elastography, or shear wave elastography. Results: The study enrolled 14,985 Chinese adults. The agreement of MAFLD and NAFLD diagnoses were 83% for FLI, 95% for ultrasound, 94% for both CAP and MRI-PDFF, and 95% for liver biopsy. The body mass index, blood pressure and lipid levels among non-MAFLD-NAFLD patients were similar metabolic parameters (p>0.05 for all), but not the alanine aminotransferase and the proportion of patients with insulin resistance, which were significantly higher in non-MAFLD-NAFLD with significant fibrosis. Conclusions: The new MAFLD definition ruled out 5-17% of NAFLD cases. NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD. Non-MAFLD-NAFLD patients with significant fibrosis had more severe liver injury and increased glycemic dysregulation within the normal range. Attention should be paid to its progression.

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation.

BACKGROUND: Traditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately. METHODS: The retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters. RESULTS: 1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters. CONCLUSION: The novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications.

Clinicopathological characteristics and survival analysis of primary duodenal cancers: a 14-year experience in a tertiary centre in South China.

BACKGROUND: Primary duodenal cancer (PDC) is rare and few studies have addressed it adequately, especially in China. The present study is to evaluate the clinicopathological features and prognosis of PDC in Chinese patients. PATIENTS AND METHODS: All the consecutive cases confirmed as PDC by histopathological analysis in The First Affiliated Hospital of Sun Yat-sen University between 1995 and 2008 were included. Clinicopathological details were retrospectively analysed and prognostic factors influencing survival were evaluated. RESULTS: The patient cohort included 53 men and 38 women, accounting for only 0.02% of all in-patients during this period. Esophagogastroduodenoscopy and gastrointestinal barium radiography were mainstay diagnostic tests for PDC; they detected 88.6% and 83.3% of the tumours, respectively. Tumours mainly occurred in the descending portion of the duodenum (67.0%). Abdominal pain was the most frequent symptom (56.0%). Histologically, adenocarcinoma was the most common type (74.7%). The overall 1-, 3- and 5-year survival rates were 62.6%, 43.7% and 33.1%, respectively. Patients survived longer in the curative surgery group (median survival time of 45 months) than those in the palliative group (6 months) (P < 0.001). Nodal metastasis and positive resection margin had a significant negative impact on survival in patients undergoing potentially curative surgery in a univariate and multivariate model (P < 0.05). CONCLUSION: Patients with PDC are rare and lack specific presentations. Esophagogastroduodenoscopy and gastrointestinal barium radiography are effective in screening this rare tumour. Nodal metastasis and positive resection margins are associated with a poor prognosis. A curative surgery that achieves complete resection with negative margin should be pursued.

[Imbalance of CD4(+) T cell subgroups in ulcerative colitis].

OBJECTIVE: To investigate the relationship of the imbalance of CD4(+) T cell subgroups and the pathogenesis of ulcerative colitis (UC). METHODS: Peripheral blood samples were collected from 24 UC patients and 17 healthy donors. Then the phenotype of CD4(+) T cells and the major transcription factor expression of each subset were analyzed by flow cytometry and real-time PCR (polymerase chain reaction) respectively. The serum concentrations of major cytokines of each subgroup were measured by cytometric bead array (CBA) and ELISA (enzyme-linked immunosorbent assay). RESULTS: (1) The proportion of Treg cells in the UC group was lower than the control group (6.7% ± 1.7% vs 7.9% ± 1.4%, P = 0.016), especially in active stage (6.4% ± 1.7%, P = 0.005). As compared with the control group, the expression of FOXP3 mRNA was lower in the UC Group (P = 0.020). And so was the serum concentration of TGF-ß1 [(21 ± 8) µg/L vs (28 ± 7) µg/L, P = 0.026]. (2) There were no significant differences in Th1-related transcription factors and cytokines between two groups. (3) Th2 cells were higher in the UC group (2.7% ± 1.1% vs 1.6% ± 0.4%, P = 0.002), especially in active stage (2.8% ± 1.0%, P = 0.001). The expression of GATA-3 mRNA was 4.4 folds higher than that of the controls (P = 0.045). (4) Th17 cells were higher in the UC group (3.4% ± 1.8% vs 1.8% ± 0.7%, P = 0.005). And the RORγt mRNA expression was 13 folds higher in UC group (P = 0.001); the serum concentrations of IL-6 and IL-17 were higher in the UC group (both P < 0.05). (5) The ratios of Treg/Th2 and Treg/Th17 were significantly lower in the UC group and associated with disease activity (both P < 0.05). CONCLUSION: The imbalances of Th2, Treg and Th17 subgroups may play pivotal roles in the pathogenesis of UC.

Apolipoproteins and liver parameters optimize cardiovascular disease risk-stratification in nonalcoholic fatty liver disease.

BACKGROUND: Advanced Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). AIM: We determine whether combinations of ultrasound graphic steatosis grades, fibrosis scores and apolipoprotein levels add value to CVD risk prediction in NAFLD patients. METHODS: The retrospective cohort study enrolled 10,453 individuals (3519 NAFLD; 6934 non NAFLD) from 2004 to 2018. Hepatic ultrasound measurements, lipid and apolipoprotein profiles, Fibrosis-4 and the NAFLD fibrosis scores (NFS) were assessed. The primary outcome included both clinical and subclinical CVD. RESULTS: During 116-month follow-up period, there were 957 clinical and 752 subclinical CVD events. NAFLD patients had a higher incidence of CVD than non NAFLD patients as the steatosis degree, NFS, and FIB4 scores increased (25.1% vs 11.9%, Log Rank: p < 0.001). For the lipid and apolipoprotein profiles excluding triglyceride or ApoE, subjects with varied steatosis severity in the upper two tertiles had different risk of CVD (p for interaction < 0.001). A nomogram model combination of Framingham Risk Score (FRS), NFS and apolipoprotein profiles presented a higher AUC than FRS in a time-dependent ROC curve (0.816 vs 0.752, p < 0.001). CONCLUSION: The novel risk score considering ultrasonography-defined steatosis grades, non-invasive liver fibrosis scores and apolipoprotein profiles accurately predicted the 10-year risk of CVD.

Endoscopic management of foreign bodies in the upper gastrointestinal tract in South China: a retrospective study of 561 cases.

OBJECTIVES: Ingestion of a foreign body (FB) is a common occurrence; however, few studies have reported its characteristics and endoscopic management in South China. The aim of this study is to investigate the clinical features of FB ingestion in South China and report its management through endoscopy. METHODS: Data were collected from all consecutive patients with suspected FB ingestion accepting endoscopic management in our endoscopy center during the past 10 years. The demographic data, clinical presentations, and endoscopic management were reviewed and analyzed retrospectively. RESULTS: A total of 561 patients with suspected FB ingestion underwent endoscopic management. Among them, 447 FBs were found in 439 (78.3%) patients. Fish bone ingestion was most common (60.4%). Most of the FBs were located in the esophagus (84.5%). The majority of patients (96.1%) were successfully treated with flexible endoscopy with the addition of suitable devices without any serious procedure-related complications. There was a significant difference in the types of FBs between the former and latter 5 years (P < 0.05), and fish bone ingestion became more prevalent with time. Compared with the conventional methods, a new technique with a reworked transparent cap was successful in dealing with small sharp FBs impacted at the entrance of esophagus. The new technique had a shorter operation time (11.7 versus 17.9 min, P = 0.02) and an increased success rate (by 8%). CONCLUSIONS: In South China, fish bone is the most common FB found in the upper gastrointestinal tract. Endoscopic management is a safe and effective approach in managing FBs. A new technique with reworked transparent cap is useful and promising, but further study is needed for confirmation.

Distinct Cause of Death Profiles of Hospitalized Non-alcoholic Fatty Liver Disease: A 10 Years' Cross-Sectional Multicenter Study in China.

Background: The clinical burden and natural history of non-alcoholic fatty liver disease (NAFLD) vary globally. We aimed to investigate NAFLD-related mortality profiles in hospitalized patients in southern China. Methods: A multicenter retrospective investigation with a 10-year study period (2009-2018) analyzed 10,071 deaths during hospitalization (NAFLD: 2,015; other liver diseases: 1,140; without liver diseases: 6,916) was performed using a multiple cause of death analysis. Medical histories and biochemistry and imaging findings were extracted from the electronic medical record system. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases (ICD-10) codes. Results: The distribution of death causes in patients with NAFLD has stabilized over time, with cardio- and cerebral vascular disease (CVD) ranked first (35.6%), followed by extrahepatic malignancies (22.6%), infection (11.0%), kidney disease (7.5%), liver-related diseases (5.2%), respiratory diseases (3.9%), digestive diseases (3.5%), endocrine diseases (3.5%), and other diseases (7.2%). NAFLD patients had more deaths attributable to CVD, extrahepatic malignancies, liver-related diseases (all P < 0.001) and multiorgan failure than the deceased controls. The severity of steatosis was independently associated with these relationships (liver-related diseases: OR = 1.37, 95% CI: 1.20-1.59, cardio- and cerebrovascular diseases: OR = 1.23, 95% CI: 1.19-1.31, infectious diseases: OR = 1.14, 95% CI: 1.04-1.26, and renal diseases: OR = 1.21, 95% CI: 1.02-1.47, all P < 0.05) after adjustment for sex, body mass index (BMI), fasting blood glucose, low-density lipoprotein cholesterol, uric acid, metabolic syndromes and fibrosis index based on the 4 factors. Conclusion : NAFLD patients had higher proportions of death due to underlying CVD and liver-related diseases than the general population in China; these proportions positively correlated with steatosis degree.

Changes on the disease pattern of primary colorectal cancers in Southern China: a retrospective study of 20 years.

PURPOSE: Some changes on the disease pattern of colorectal cancer (CRC) have occurred in some Asian countries recently. However, nothing is known about it in China lately. The present study is to determine whether there are any changes on the disease pattern of CRC in Southern China. PATIENTS AND METHODS: Data were collected from all consecutive patients accepting colonoscopy in our endoscopy center during the last 20 years. The sociodemographic data, clinical presentations, endoscopic descriptions, and histological subtypes of patients confirmed as CRC by pathology were analyzed retrospectively. RESULTS: A total of 37,578 patients accepted colonoscopy from 1987 to 2006, in which 2,876 patients were diagnosed as CRC. The median age of patients in the 2nd decade (1997-2006; 62 years) was getting older than the 1st decade (1987-1996; 58 years; P = 0.043). Hematochezia was the most frequent symptom (55.8%), while rectum was the most common site distribution of CRC (51.0%). The incidence of right-sided colonic cancers in the 2nd decade (21.0%) was higher than the 1st decade (17.3%; P = 0.0314). Histologically, adenocarcinoma was the most common (92.4%), of which moderately differentiated tumors were more frequent (67.7%). CRCs with high-grade malignancy were more likely to occur in the 1st decade (P < 0.0001). CONCLUSIONS: Rectum remains the most common site of CRC in southern China. But a rightward shift in the site distribution has occurred and patients are getting older. Tumors with high-grade malignancy have the tendency to decrease.

Prevalence of lactose intolerance in patients with diarrhea-predominant irritable bowel syndrome: data from a tertiary center in southern China.

BACKGROUND: Symptoms associated with lactose intolerance (LI) and diarrhea-predominant irritable bowel syndrome (IBS-D) are almost the same. These disease entities are difficult to differentiate clinically. In practice, differential diagnosis depends on self-reported patient milk intolerance. However, there is limited data on the prevalence of LI in China. The aim of this study was to investigate the prevalence of LI in IBS-D patients and asymptomatic healthy controls. METHODS: Lactose malabsorption (LM) was diagnosed by a lactose hydrogen breath test (HBT) and was defined by peak breath H2 excretion over the baseline level of ≥ 20 ppm. LI-related symptoms were monitored for 8 h following lactose administration. LI was defined in LM patients with positive symptoms during the observation time. Patients with IBS-D were additionally asked if they were intolerant to milk. RESULTS: A total of 109 eligible IBS-D patients (Rome III criteria) and 50 healthy controls were enrolled in this study. Except for hydrogen non-producers, the prevalence of LM did not differ between IBS-D patients and the control group (85%, 82/96 vs 72%, 34/47; P = 0.061). There was, however, a higher LI prevalence in IBS patients than in healthy subjects (45%, 43/96 vs 17%, 8/47; P = 0.002). Sensitivity, specificity, and positive and negative predictive values of self-reported milk intolerance for detecting LI were 58, 58, 53, and 63%, respectively. CONCLUSIONS: Prevalence of LI is significantly higher in IBS-D patients than in healthy subjects. Self-reported milk intolerance is a poor diagnostic predictor of LI.

Primary Care Management of Chronic Constipation in Asia: The ANMA Chronic Constipation Tool.

Chronic constipation (CC) may impact on quality of life. There is substantial patient dissatisfaction; possible reasons are failure to recognize underlying constipation, inappropriate dietary advice and inadequate treatment. The aim of these practical guidelines intended for primary care physicians, and which are based on Asian perspectives, is to provide an approach to CC that is relevant to the existing health-care infrastructure. Physicians should not rely on infrequent bowel movements to diagnose CC as many patients have one or more bowel movement a day. More commonly, patients present with hard stool, straining, incomplete feeling, bloating and other dyspeptic symptoms. Physicians should consider CC in these situations and when patients are found to use laxative containing supplements. In the absence of alarm features physicians may start with a 2-4 week therapeutic trial of available pharmacological agents including osmotic, stimulant and enterokinetic agents. Where safe to do so, physicians should consider regular (as opposed to on demand dosing), combination treatment and continuous treatment for at least 4 weeks. If patients do not achieve satisfactory response, they should be referred to tertiary centers for physiological evaluation of colonic transit and pelvic floor function. Surgical referral is a last resort, which should be considered only after a thorough physiological and psychological evaluation.