The American College of Gastroenterology published the clinical guideline on alcohol-associated liver disease(ALD)in January 2024 in American Journal of Gastroenterology.This guideline elaborates on the epidemiology and disease burden of ALD and alcohol use disorder,the risk factors for ALD,the diagnosis and treatment of alcohol use disorder,the disease spectrum of ALD,the management of ALD,and public policy and prevention.This article gives an excerpt of the recommendations and key points/statements in this guideline.

OBJECTIVE: To carry out genetic analysis for 21 patients with methylmalonic acidemia (MMA) and provide genetic counseling for their families. METHODS: Next generation sequencing (panel) was used to detect the pathogenic variants underlying the disease. RESULTS: In total 29 variant sites of MMUT, MMAA, MMUT were identified in the 21 patients, with common variants including c.323G>A (10%), c.917C>T (10%), c.984delC (10%) of MMUT gene, and c.609G>A (45%), c.80A>G (10%) , c.567dupT (10%) of MMACHC gene. Among these, c.2000A>G of MMUT, c.298G>T of MMACHC and c.734-7A>G of MMAA gene were unreported previously. CONCLUSION Genetic testing for MMA patients can clarify the cause of the disease and provide a basis for the clinical diagnosis. Discovery of novel variants has enriched the mutational spectrum of MMA.
Amino Acid Metabolism, Inborn Errors/genetics* ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Oxidoreductases/genetics*

Background Essential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. Objective To evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. Methods A prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. Results The positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. Conclusion Exposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.

Humans ; Air Pollutants ; Sleep Apnea, Obstructive ; Polysomnography ; Sleep ; Pulmonary Disease, Chronic Obstructive

The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep under-standing of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provided the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16％and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNA genes were identified. They were associated with effector, exhausted, and regulatory T cell states. Moreover, 84 of them were functionally annotated based on the co-expression networks, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.

Gilbert’s syndrome is a kind of benign inherited disease of bilirubin binding disorder, mainly due to the homozygous polymorphism A(TA)7TAA in the promoter of the gene for uridine diphosphate -glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter, designated as UGT1A1*28, with UGT activity reduction to 30% of the normal value. Therefore, circulating fat-soluble unconjugated bilirubin cannot be converted into water-soluble conjugated bilirubin, leading to unconjugated hyperbilirubinemia. Bilirubin has a strong affinity for erythrocyte phospholipids, which interferes with membrane composition and dynamics, resulting in increased erythrocytes fragility, easy rupture, and gradual shortening of survival time. However, there are no obvious sign of hemolysis or abnormal iron metabolism, erythrocytes and bone marrow morphology. A small amount of chronic hemolysis stimulates extramedullary (normal bone marrow morphology) hematopoiesis, ensuing compensatory increase in circulating erythrocytes and hemoglobin. Hyperbilirubinemia may also weaken gastrointestinal motility, increase passive diffusion and absorption across the intestinal mucosal epithelium by 1.5 to 2 times, thereby aggravating or worsening hyperbilirubinemia mainly with unconjugated bilirubin circulation, which indicates that there is a causal relationship between the circulating bilirubin concentration and rapid erythrocytes turnover and hemolysis rate in patients with Gilbert’s syndrome. Interestingly, bilirubin also has significant antioxidant and anti-mutagenic activities, and the potential health benefits of mild hyperbilirubinemia in Gilbert's syndrome include reduced prevalence of cardiovascular disease, type 2 diabetes mellitus (and related risk factors), certain cancers, and cardiovascular-related and all-cause mortality. Exogenous bilirubin and biliverdin supplements in intestinal epithelial cells can be absorbed and may increase circulating concentration of these antioxidant compounds. With this information, we hope to raise awareness of the potentially harmful and beneficial effects of benign hyperbilirubinemia, and explore and develop beneficial medical interventions.

Non-alcoholic fatty liver disease and alcohol (ethanol)-related liver disease is a global epidemic of chronic liver disease and the main cause of fatty liver. Non-alcoholic fatty liver patients sometimes ingest different types of alcohol. Therefore, when obesity coexist with alcohol consumption, it is more difficult to diagnose the cause of fatty liver. The amount of alcohol consumption and alcohol drinking pattern and chronic liver injury, type 2 diabetes mellitus, cardiovascular disease and other metabolic-related diseases may have J-type correlation; that is to say, a light to moderate amount of alcohol consumption may bring certain benefits to the above diseases, but excessive alcohol consumption may promote the development of obesity, aggravate liver disease, metabolic abnormalities, and increase the risk of tumors. Screening for metabolic-related disease risk should be considered in addition to the assessment of changing liver lesions when obesity coexists with alcohol consumption. Changing bad living habits, losing weight and abstaining from alcohol are still the basis of treating fatty liver and metabolic disorders. Carefully selecting patients and communicating with them about the risk and benefit of drugs are important indicators of drug therapy. Patients with end-stage liver disease can be considered for liver transplantation and postoperative lifestyle improvement should be emphasized.

Rapid progression or aggravation of jaundice, coagulation abnormalities and liver-related complications in patients with alcoholic hepatitis indicates that they may develop severe alcoholic hepatitis. Some of these patients can progress acute-on-chronic liver failure with acute insults, such as infection and binge drinking and binge, showing as acute decompensation, organ failure and high 28-day mortality rate. Early identification and effective intervention can improve the prognosis of acute-on-chronic liver failure. Intestinal barrier dysfunction and liver-gut axis imbalance play an important role in the development of severe alcoholic hepatitis and acute-on-chronic liver failure. It is important to improve the basic nutritional status of patients. Effective drug therapies are limited in improving the condition and prognosis of acute-on-chronic liver failure. Early liver transplantation can bring great benefits to these patients.

Objective To explore the protective effect and mechanism of hydrogen-rich water (HRW) on ethanol-induced acute gastric injury.Methods The experimental study was conducted.Forty kunming mice were divided into the 4 groups by random number table method:normal control group [0.01 mL/g normal saline (NS)+ 0.03 mL/g NS],HRW group (0.01 mL/g NS +0.03 mL/g HRW),ethanol model group (0.01 mL/g 56°alcoholic drinks +0.03 mL/g NS),HRW treated group (0.01 mL/g 56°alcoholic drinks +0.03 mL/g HRW).Ten mice in each group were administrated twice a day for 7 days.Testing indicators:(1) gastric ulcer index was measured,(2) pathological examination of gastric tissues,(3) activity of serum superoxide dismutase (SOD) and expressions of malondialdehyde (MDA),interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were measured,(4) expressions of SOD and MDA in gastric tissues were measured,(5) protein expressions of apoptosis related factors (caspase-3,bax,caspase-9,fas and caspase-8) in gastric tissues were measured by immunohistochemistry,(6) relative expressions of mRNA of apoptosis related factors (caspase-3,bax,caspase-9,fas and caspase-8) in gastric tissues were measured by realtime polymerase chain reaction (RT-PCR).Measurement data with normal distriburion were presented as (x)±s.Comparisons among groups were done using the one-way ANOVA and comparison between groups was done using the LSD-t test.Results (1) Gastric ulcer index was measured:gastric ulcer index of mice in the normal control group,HRW group,ethanol model group and HRW treated group were respectively 0,0,10.40± 1.64 and 3.92 ± 0.23,with statistically significant differences (F=175.050,P＜0.05).There was a statistically significant difference between the ethanol model group and normal control group or HRW treated group (t =19.835,12.352,P＜ 0.05).(2) Pathological examination pathological examination of gastric tissues:① Macropathology of gastric tissues:the surface of the gastric mucosa was normal and smooth in the normal control group and the HRW group,without ulcer,erosion and inflammation.The partial gastric mucosal erosion and ulcer in the ethanol model group was large and very severe.Compared with the ethanol model group,the area of gastric mucosal lesion was reduced in the HRW treated group.② Results of pathological examination of gastric tissues:gastric mucosa in the normal control group and HRW group were integrity.Compared with the normal control group,the partial gastric surface epithelium was degenerate and impaired in the ethanol model group.Compared with the ethanol model group,the gastric mucosal erosion and inflammatory cell infiltration were alleviated in the HRW treated group.(3) Expressions of serum SOD,MDA,IL-6 and TNF-α:expressions of serum SOD,MDA,SOD/MDA and IL-6 were respectively (70±6)U/mL,(7.52±0.23) μmol/L,9.40 ± 1.07,(6.3 ± 1.8) ng/L in the normal control group and (74 ± 4) U/mL,(7.61 ±0.91) μmol/L,9.91 ± 1.55,(5.1 ± 1.6)ng/ L in the HRW group and (101 ± 4) U/mL,(16.95 ± 0.66) μmol/L,5.99±0.17,(19.2±4.9) ng/L in the ethanol model group and (115±5) U/mL,(14.02±0.58) μmol/L,8.23±0.32,(7.1±1.8)ng/L in the HRW treated group,with statistically significant differences among the 4 groups (F=97.405,269.950,16.486,25.663,P＜0.05).The serum TNF-α levels were respectively (53± 14) ng/L,(67± 17) ng/L,(52± 13) ng/L,(58±21) ng/L in the above 4 groups,with no significant difference (F=0.862,P＞0.05).(4) Expressions of SOD and MDA in gastric tissues were measured:expressions of SOD and MDA and SOD/MDA were respectively (93 ± 18) U/mL,(7.90± 1.72) μmol/L,12.48±4.54 in the normal control group and (93±13) U/mL,(6.96± 1.49) μmol/L,13.83±3.40 in the HRW group and (121±31) U/mL,(17.10±4.88) μmoL/L,7.88± 3.70 in the ethanol model group and (143 ± 26) U/mL,(7.31 ± 1.58) μmoL/L,20.00±4.68 in the HRW treated group,with statistically significant differences among the 4 groups (F=5.463,15.051,7.388,P＜ 0.05).(5) The expressions of apoptosis related factors in gastric tissues:the results of immunohistochemistry showed that the levels of caspase-3,bax and fas were repectively 0.065 5± 0.003 7,0.065 7±0.003 0,0.225 4±0.024 3 in the normal control group and 0.065 7±0.002 7,0.064 9±0.003 0,0.246 0±0.022 3 in the HRW group and 0.330 7±0.017 3,0.335 4±0.033 3,0.397 0±0.028 5 in the ethanol model group and 0.096 7±0.003 0,0.084 8±0.001 7,0.375 0±0.035 6 in the HRW treated group,showing statistically significant differences among the 4 groups (F=1 004.222,309.171,48.555,P＜0.05).The levels of caspase-9 and caspase-8 were respectively 0.049 2±0.000 4,0.151 5±0.010 2 in the normal control group and 0.047 9±0.002 0,0.154 00.013 5 in the HRW group and 0.047 0±0.003 7,0.157 2±0.006 2 in the ethanol model group and 0.048 7±0.000 8,0.153 9±0.006 3 in the HRW treated group,with no statistically significant difference among the 4 groups (F=0.998,0.297,P＞0.05).(6) The mRNA expressions of apoptosis related factors in gastric tissues:resutls of RT-PCR showed that relative expressions of mRNA of caspase-3,bax,caspase-9 and fas were respectively 1.00±0.00,1.00±0.00,1.00±0.00,1.00±0.00 in the normal control group and 0.72±0.43,0.66±0.26,1.57±0.31,0.50±0.19 in the HRW group and 3.19±0.87,1.58±0.76,3.04± 1.15,2.84±0.98 in the ethanol model group and 0.49±0.16,0.69±0.25,2.98±0.85,0.53±0.24 in the HRW treated group,showing statistically significant differences among the 4 groups (F=32.106,5.038,9.706,23.387,P＜0.05).The mRNA levels of caspase-8 were respectively 1.00±0.00,1.50±0.60,1.36±0.34,1.32±0.43 in normal control group,HRW group,ethanol model group and HRW treated group,with no significant difference among the 4 groups (F=1.337,P＞0.05).Conclusions Hydrogen-rich water could alleviate ethanolinduced acute gastric injury by antioxidant,anti-inflammatory and anti-apoptosis.Hydrogen-rich water is safe and reliable,without toxic and side effects on the body.

Objective To assess the effectiveness of iterative metal artifact reduction (IMAR) on metal artifacts reduction in thorax scan.Methods Thoracic phantom with two pedicle screws implanted in both sides of the T5 vertebrae was used,with the scan parameters of 130 kV and CARE Dose 4D,the phantom was scanned with and without the screws respectively.Images without screws were reconstructed with FBP.Images with screws were reconstructed with FBP and IMAR respectively.Three ROIs were selected on tissues including aorta,pulmonary and paravertebral soft tissue on image slice adjacent to the screws.The CT value and standard deviations (noise) of ROIs were measured,and the deviation of CT value (△HU) was calculated as the difference between CT values in images with and without screws.Twenty-six cases who received chest CT examination and with pedicle screw implant in scanning range were collected.The scanning parameters and image reconstruction methods were the same as phantom scan.The CT value (HU) of metal artifacts adjacent to vertebrae and dorsal soft tissue was measured,and the image quality of reconstructed image by two skilled radiologists independently was evaluated.Results In the phantom after implanted screws,the noise were significantly reduced by IMAR compared to FBP in all the three ROIs of aorta,pulmonary and paravertebral soft tissue (P＜0.05),and the △HU was significantly smaller in IMAR compared to that with FBP (P＜0.01).In 26 patients,there were significant differences in CT value of vertebral bone tissue and dorsal soft tissue between FBP and IMAR (P＜0.05),and the subjective evaluation scores of the two image reconstruction methods showed a statistically significant difference (P＜0.05).Conclusion IMAR can significantly reduce streak artifacts of metal implant and adjuste the CT values of artifact affected tissues to make it more close to the true value without metal implant.