Humans ; COVID-19 ; Alanine Transaminase ; Aspartate Aminotransferases ; Prognosis

L-glutamic acid is the world's largest bulk amino acid product that is widely used in the food, pharmaceutical and chemical industries. Using Corynebacterium glutamicum G01 as the starting strain, the fermentation by-product alanine content was firstly reduced by knocking out the gene encoding alanine aminotransferase (alaT), a major by-product related to alanine synthesis. Secondly, since the α-ketoglutarate node carbon flow plays an important role in glutamate synthesis, the ribosome-binding site (RBS) sequence optimization was used to reduce the activity of α-ketoglutarate dehydrogenase and enhance the glutamate anabolic flow. The endogenous conversion of α-ketoglutarate to glutamate was also enhanced by screening different glutamate dehydrogenase. Subsequently, the glutamate transporter was rationally desgined to improve the glutamate efflux capacity. Finally, the fermentation conditions of the strain constructed using the above strategy were optimized in 5 L fermenters by a gradient temperature increase combined with a batch replenishment strategy. The glutamic acid production reached (135.33±4.68) g/L, which was 41.2% higher than that of the original strain (96.53±2.32) g/L. The yield was 55.8%, which was 11.6% higher than that of the original strain (44.2%). The combined strategy improved the titer and the yield of glutamic acid, which provides a reference for the metabolic modification of glutamic acid producing strains.
Glutamic Acid ; Corynebacterium glutamicum/genetics* ; Ketoglutaric Acids ; Metabolic Engineering ; Alanine

OBJECTIVE: To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. METHODS: Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. RESULTS: No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). CONCLUSION A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.
Pregnancy ; Humans ; Female ; Infertility, Female/genetics* ; Endometrium/metabolism* ; Amino Acids/metabolism* ; Gene Expression ; Carnitine ; Alanine/metabolism* ; Valine/metabolism*

OBJECTIVES: To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration. METHODS: A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment. RESULTS: After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05). CONCLUSIONS A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.
Humans ; Child ; Hepatolenticular Degeneration/therapy* ; Alanine Transaminase ; Copper ; Food ; Aspartate Aminotransferases

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

OBJECTIVE: To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice. METHODS: The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury. RESULTS: A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest. CONCLUSIONS The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.
Humans ; Prognosis ; Retrospective Studies ; Interleukin-6 ; ROC Curve ; Sepsis/diagnosis* ; Heat Stroke/complications* ; Risk Factors ; Alanine Transaminase ; Creatine Kinase, MB Form ; Lactic Acid ; Creatine Kinase

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.
Female ; Humans ; Pregnancy ; Infant ; Blood Pressure ; Pre-Eclampsia/diagnosis* ; Prospective Studies ; Gestational Age ; Alanine Transaminase ; Hemoglobins

This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Chlorogenic Acid ; Acetaminophen ; Chemical and Drug Induced Liver Injury, Chronic ; Alanine Transaminase ; MicroRNAs

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.
Female ; Humans ; Child ; Glucocorticoids ; Retrospective Studies ; Hepatitis, Autoimmune/drug therapy* ; Alanine Transaminase ; Osteomyelitis/drug therapy*

Objective: To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B (CHB) and further explore the optimal ALT threshold strategy for initiating antiviral therapy. Methods: Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected. Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes (≥G2/S2). Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis ≥ S2. Results: A total of 447 eligible CHB patients, with a median age of 38.0 years and 72.9% males, were included. During ALT normalization, there was significant liver inflammation (≥G2) and fibrosis (≥S2) in 66.9% and 53.0% of patients, respectively. With an ALT rise of 1-2×ULN, the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2% and 60.0%, respectively. After adjusting for confounding factors, higher ALT levels (> 29 U/L) were found to be associated with significant liver inflammation (OR: 2.30, 95% CI: 1.11 ~ 4.77) and fibrosis (OR: 1.84, 95% CI: 1.10 ~ 3.09). After the measurement of glutamyltransferase-platelet ratio (GPR), the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards, and in particular, the erroneous evaluation of liver fibrosis≥S2 was significantly improved (33.5% to 57.5%). Conclusion: More than half of CHB patients have a normal ALT or one within 2 × ULN, regardless of whether or not there is apparent inflammation and fibrosis. GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.
Male ; Humans ; Adult ; Female ; Hepatitis B, Chronic/complications* ; Alanine Transaminase ; Retrospective Studies ; Liver/pathology* ; Liver Cirrhosis/complications* ; Inflammation/pathology* ; Hepatitis B e Antigens