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Jiaofeng Huang,1,&ast; Wenjuan Xue,2,&ast; Mingfang Wang,1 Yinlian Wu,1 Medha Singh,3 Yueyong Zhu,1,4 Rahul Kumar,5 Su Lin1 1Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350005, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, People’s Republic of China; 3Department of General Medicine, Tan Tock Seng Hospital, Singapore; 4Fujian Key Laboratory of Precison Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Department of Gastroenterology and Hepatology, Duke-NUS Academic Medical Centre, Changi General Hospital, Singapore&ast;These authors contributed equally to this workCorrespondence: Su LinDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of ChinaTel +86 591-87981657Fax +86 591-87982526Email sumer5129@fjmu.edu.cnIntroduction: Metabolic associated fatty liver disease (MAFLD) is a novel concept for fatty liver disease. Different from non-alcoholic fatty liver disease (NAFLD), the diagnosis of MAFLD requires the presence of metabolic risks. This study aimed to characterize patients with liver steatosis but without metabolic risks (non-MR-steatosis) which may not be diagnosed by MAFLD criteria.Methods: Consecutive patients who underwent biopsy were included in this study. The clinic-pathological characteristics of non-MR-steatosis, NAFLD and MAFLD were compared.Results: A total of 1217 cases were included. There were 426 (35.00%) cases with MAFLD, 585 (48.07%) with NAFLD and 168 (13.80%) with non-MR-steatosis. The majority of the cases were infected with HBV (93.26%). The age and metabolic profiles were highest in MAFLD and lowest in non-MR-steatosis. The body mass index (BMI) level was also lowest in non-MR-steatosis (20.78 ± 1.54 kg/m2). The ALT and AST levels of the non-MR-steatosis group were not statistically different from those of MAFLD or NAFLD groups (p > 0.05). Histologically, there was no significant difference in the degrees of inflammation and fibrosis among the three groups. The severity of steatosis in non-MR-steatosis group was lower than MAFLD or NAFLD groups (p < 0.05). These results were consistent in both HBV and non-HBV subgroups.Conclusion: MAFLD criteria may overlook some steatotic patients without metabolic risks, who may also have steatohepatitis and significant fibrosis.Keywords: metabolic associated fatty liver disease, nonalcoholic fatty liver disease, metabolic risks, lean NAFLD, biopsy

Jiaofeng Huang,1 Weijie Ou,1 Mingfang Wang,1 Medha Singh,2 Yuxiu Liu,1 Shiying Liu,1 Yinlian Wu,1 Yueyong Zhu,1,3 Rahul Kumar,4,* Su Lin1,* 1Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of General Medicine, Tan Tock Seng Hospital, Singapore; 3Fujian Key Laboratory of Precison Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Department of Gastroenterology and Hepatology, Duke-NUS Academic Medical Centre, Changi General Hospital, Singapore*These authors contributed equally to this workCorrespondence: Su LinDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of ChinaEmail sumer5129@fjmu.edu.cnBackground and Aims: Metabolic associated fatty liver disease (MAFLD) is diagnosed in patients with hepatic steatosis when they have the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. There is no clarity whether subtypes of MAFLD diagnosed by different metabolic conditions carry different levels of risk for intra- and extra-hepatic organs. This study aims to depict the characteristics of these subtypes in a large population.Methods: The data were retrieved from the third National Health and Nutrition Examination Surveys of the United States. The clinical and biochemical features in different MAFLD subtypes were compared. The outcome of interest was significant and advanced fibrosis.Results: Out of 4,087 (31.24%) participants with MAFLD, 1,165 (28.51%) were diagnosed by single metabolic condition, 2,053 (50.23%) by two conditions, and 869 (21.26%) by all three metabolic conditions. With increasing numbers of metabolic conditions, participants tended to be older, were more likely to be female, and had more severe renal impairment and liver fibrosis (P< 0.05). MAFLD patients with a lower number of metabolic conditions were more likely to have excessive alcohol consumption. Among MAFLD with single metabolic condition, those diagnosed by diabetes alone had the highest proportion of advanced fibrosis identified by non-invasive fibrosis models (P< 0.05).Conclusion: More metabolic conditions upon the diagnosis of MALFD indicate higher risk of fibrosis. Patients with MAFLD diagnosed by diabetes alone are more likely to have advanced hepatic fibrosis than those with other metabolic conditions alone. Individualized management is required for MAFLD with different subtypes.Keywords: metabolic associated fatty liver disease, nonalcoholic fatty liver disease, metabolic syndromes, NHANES, fibrosis

Zhiyuan Weng,1 Weijie Ou,2 Jiaofeng Huang,2 Medha Singh,3 Mingfang Wang,2 Yueyong Zhu,2 Rahul Kumar,4,* Su Lin2,* 1Cardiology Department, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 2Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 3Department of General Medicine, Tan Tock Seng Hospital 308433, Singapore; 4Department of Gastroenterology and Hepatology, Duke-NUS Academic Medical Centre, Changi General Hospital 529889, Singapore*These authors contributed equally to this workCorrespondence: Su LinDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail sumer5129@fjmu.edu.cnBackground and Aims: Circadian misalignment (CM) leads to metabolic disorder. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is a novel definition for fatty liver disease that requires the presence of metabolic dysfunction. As the association between CM and MAFLD remains unclear, this study is designed to explore whether there is an association between CM and MAFLD.Methods: NHANES 2017– 2018 database was used in this study. Liver steatosis and fibrosis were diagnosed by Fibroscan®. CM was defined by the presence of mistimed sleep, late sleep or irregular chronotype. Propensity score matching (PSM) was used to match subjects for their age and gender.Results: A total of 4552 participants were included in the study, with 2089 (45.89%) identified as MAFLD and 894 (19.64%) as CM. Participants with CM were significantly younger than those without (46.06 ± 18.06 vs 50.93 ± 17.78, p< 0.001). PSM for age and gender resulted in 894 participants with CM and 892 with non-CM. CM group had higher body mass index, liver enzymes, glucose and lipid levels. The prevalence of MAFLD was higher in the CM group than the non-CM group (45.41% vs 28.48%, p< 0.001). The presence of CM increased the risk of MAFLD by more than twofold. Short sleep duration (< 6 hours) was not independently associated with MAFLD or fibrosis if additionally adjusting for CM.Conclusion: CM is independently associated with MAFLD, while short sleep duration (< 6 hours) is not an independent risk factor for MAFLD or liver fibrosis after adjusting for CM.Keywords: fatty liver disease, MAFLD, circadian, sleep, fibrosis

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease (MAFLD). AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD), and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with MAFLD. METHODS Consecutive patients with histologically confirmed MAFLD were included. The discrimination ability of different non-invasive scores was compared. RESULTS A total of 417 patients were included; 156 (37.4%) of them had advanced fibrosis (Metavir ≥ F3). The area under receiver operating characteristic curve of FIB-4, NFS, APRI, and BARD for predicting advanced fibrosis was 0.736, 0.724, 0.671, and 0.609, respectively. The area under receiver operating characteristic curve of FIB-4 and NFS was similar (P = 0.523), while the difference between FIB-4 and APRI (P = 0.001) and FIB-4 and BARD (P < 0.001) was statistically significant. The best thresholds of FIB-4, NFS, APRI, and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05, -2.1, 0.42, and 2. A subgroup analysis showed that FIB-4, APRI, and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group. CONCLUSION APRI and BARD scores do not perform well in MAFLD. The FIB-4 and NFS could be more useful, but a new threshold is needed. Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Non-steroidal anti-inflammatory agents inhibit the production of cyclooxygenase (COX) products and can attenuate bone loss. In this double-masked, placebo-controlled, randomized clinical trial, the efficacy of celecoxib (COX-2 inhibitor) was evaluated in conjunction with scaling and root planing (SRP) in subjects with chronic periodontitis (CP).A total of 131 subjects were randomized to receive SRP and either celecoxib (200 mg) or placebo every day for 6 months. Clinical outcomes were assessed every 3 months for 12 months as mean changes from baseline. Primary efficacy parameters included clinical attachment level (CAL) and probing depth (PD). Secondary outcomes included percentages of tooth sites with CAL loss or gainor =2 mm, changes in bleeding on probing (BOP), plaque index, and mobility. Prior to analysis, tooth sites were grouped based on baseline PD as shallow (1 to 3 mm), moderate (4 to 6 mm), or deep (or =7 mm).Mean PD reduction and CAL gain were greater in the celecoxib group, primarily in moderate and deep sites, throughout the study (PD: 3.84 mm versus 2.06 mm, P0.001; CAL: 3.74 mm versus 1.43 mm, P0.0001 for deep sites at 12 months). The celecoxib group also exhibited a greater percentage of sites withor =2 mm CAL gain and fewer sites withor =2 mm CAL loss. Both groups showed improved plaque control and BOP scores. Demographic, social, and behavioral factors did not affect treatment outcomes.Celecoxib can be an effective adjunctive treatment to SRP to reduce progressive attachment loss in subjects with CP. Its beneficiary effect persisted even at 6 months postadministration. However, given the increased cardiovascular risks associated with the use of this drug, close patient supervision and strict adherence to dosage and administration guidelines established by the Unites States Food and Drug Administration are of paramount importance.

The purpose of this clinical study was to compare peri-implant crestal bone levels between misfitting (overhanging/open margin) cement-retained implant single crowns (SCs) vs accurately fitted implant SCs. Seventeen subjects were divided into two groups: test group (misfitting crowns, n = 10) and control group (accurately fitted crowns, n = 7). Crestal bone level changes were assessed using digital software. The average differences in mean bone loss within and between the two groups were statistically significant. Cement-retained implant SCs with marginal misfit resulted in more crestal bone loss than accurately fitted crowns after a mean of 3 years in function.

To determine whether omega-3 (n-3) increases saliva production in patients with Sjogren's syndrome, 61 patients with Sjogren's received either wheat germ oil (n = 23) or n-3 supplement (TheraTears Nutrition®) (n = 38) in a prospective, randomized, double-masked trial. The outcomes assessed were salivary secretion and markers for oral inflammation. The differences between the n-3 group and wheat germ oil group were not statistically significant for either unstimulated (US) or stimulated (SS) salivary secretion (p= 0.38 and p= 0.346, respectively) nor for the number of sites with probing depth (PD) ≥ 4 mm (p= 0.834). In this pilot study, supplementation with n-3 was not found to be significantly better than wheat germ oil in stimulating saliva production in patients with Sjogren's syndrome.

• Sjogren’s syndrome is a chronic autoimmune disorder, most common in adult women. • There is no known etiology or cure for Sjogren’s syndrome. • Sjogren’s syndrome is characterized by debilitating ocular and oral manifestations. • Early diagnosis and palliation are critical. • Nutrition implications are similar to those for patients undergoing oral cancer and head and neck radiation. • Omega-3 fatty acids have been implicated as a potential therapeutic agent.

Background: Bleeding on probing (BOP) is a frequent observation in patients with Sjögren′s syndrome and a sialagogue is routinely prescribed for these patients. Objective: The objective of this study was to evaluate the effect of sialagogue (muscarinic cholinergic agonists) on BOP in patients with Sjögren′s syndrome. Materials and Methods: This observational study included 57 subjects. Study population was divided into two groups: Subjects on sialagogue (n = 32) and subjects not on sialagogue due to their side-effects (non-sialagogue, n = 25). The number of sites with BOP was recorded on all teeth. Results: The subjects on sialagogue had a significantly lower mean (standard error) number of sites with BOP 22.97 (2.65) as compared with the non-sialagogue group 46.59 (6.20), P < 0.001. After adjusting for the use of remineralizing rinse the subjects on sialagogue had a significantly lower number of sites with BOP (P < 0.001). Conclusion: In this observational study treatment with sialagogue may prevent BOP in patients with Sjögren′s syndrome.

The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures.On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety.Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P.0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups.PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits.Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.