High-dose pulse methylprednisolone vs. dexamethasone standard therapy for severe and critical COVID-19 pneumonia: Efficacy assessment in a retrospective single-centre experience from Malaysia.

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP. MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups). RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23). CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.

[A new concept from a global perspective for expanding the treatment of chronic hepatitis B].

The global chronic hepatitis B (CHB) guidelines have gradually expanded treatment indications in order to accelerate the elimination and improve the treatment rate of hepatitis B virus (HBV) infection. This article analyzes the new treatment concepts for chronic hepatitis B at home and abroad from two aspects: expanding treatment by paying more attention to the long-term prognosis of the disease and maximizing the use of existing drugs in order to achieve the early goal of the World Health Organization's of eliminating viral hepatitis by 2030.

[Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines].

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

[Histopathological evaluation of cirrhosis reversal].

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

[Different treatment strategies in patients with HBeAg-positive and negative chronic hepatitis B].

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Serum fibrinogen-like protein 1 as a novel biomarker in polycystic ovary syndrome: a case-control study.

PURPOSE: To investigate the relationship between fibrinogen-like protein 1 (FGL-1) concentrations and various metabolic characteristics in patients with polycystic ovary syndrome (PCOS) and explore whether FGL-1 could be a predictive biomarker for PCOS. METHODS: This case-control study included 136 patients with PCOS and 34 normal controls recruited in the Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital between May 2017 and June 2021. Anthropometric characteristics, metabolic parameters, and reproductive hormones were collected. Serum FGL-1 measurement was conducted using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum FGL-1 concentrations were higher in patients with PCOS than in control subjects in body mass index (BMI) subgroups, insulin resistance (IR) subgroups, and hepatic function subgroups, respectively. Serum FGL-1 concentrations were significantly associated with BMI, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-c), and serum uric acid (SUA) in all individuals. The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff value for FGL-1 levels to predict PCOS was 21.02 ng/ml with a sensitivity of 74.3% and a specificity of 70.6%. Both univariate and multiple logistic regressions indicated that the odds ratio (OR) for PCOS significantly increased in the subjects with high levels of FGL-1. CONCLUSION: In our study, FGL-1 was associated with serum aminotransferase and various metabolic indexes. Moreover, the high risk of PCOS was independently associated with the increased FGL-1 levels, which suggested that FGL-1 could be a predictive biomarker for PCOS.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

[Paying attention to other systemic diseases of hepatic manifestations: a return to common sense in clinical practice].

Liver have complex functions with a high workload. Various liver diseases are the result of the interaction of diverse genetic and environmental factors. Moreover, other systemic diseases may also affect liver, producing corresponding manifestations, such as abnormal liver function tests, portal vein or hepatic vein thrombosis, portal hypertension, hepatosplenomegaly and liver space-occupying lesions. Therefore, it is extremely important for hepatologists to have an in-depth understanding of other systemic diseases of hepatic manifestations, especially hematologic, connective tissue, endocrine, and circulatory, in order to improve the level of clinical diagnosis and treatment.

[Expanding antiviral therapy for chronic hepatitis B: scale up screening and treatment].

The Chinese Society of Hepatology, Chinese Medical Association published "Expert Opinions on Expanding Antiviral Therapy for Chronic Hepatitis B" in 2022, with a focus on "active screening of the existing patients, paying attention to the potential risk of disease progression, and active intervening of the low level viremia," and recommended that specific actions be taken to further optimize the expanding screening, widening the antiviral indications, and scale up the diagnosis and treatment of low level viremia.

[Reversal of hepatic fibrosis: more evidence and more challenges].

Hepatic fibrosis is a response to various types of hepatic injury, which can lead to cirrhosis and its complications. In recent years, in patients with viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, autoimmune liver disease and others the fibrosis or even early cirrhosis can be regressed if the etiology are controlled. Liver biopsy is still the gold standard for assessing fibrosis reversal, but non-invasive methods such as transient elastography hold great promise due to the ease to use for dynamic monitoring. Mechanisms of hepatic fibrosis reversal include extracellular matrix degradation, hepatocyte regeneration, and vascular remodeling. Presently, novel agents targeting the steps of fibrosis are urgently need for achieving regression of liver fibrosis.

[Analysis of change in esophageal varices and clinical characteristics in hepatitis B virus-related cirrhosis after antiviral therapy].

Objective: To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis. Methods: Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data. Results: All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% (χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices (χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion: After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

[Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatment].

Objective: Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients. Methods: Treatment-naïve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis. Results: Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably (P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression (OR=0.887, 95%CI: 0.802-0.981, P=0.020). Conclusions: After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis.

AIMS: This study aimed to compare the bone mineral densities (BMDs) among male patients with latent autoimmune diabetes in adults (LADA), classical type 1 diabetes (T1DM), and type 2 diabetes (T2DM), and to examine the risk factors for developing low BMD in these patients. PATIENTS AND METHODS: Between January 2017 and October 2020, a total of 57, 67, and 223 male patients with LADA, classical T1DM, and T2DM, respectively, were recruited from the endocrinology department of Shanghai Tenth People's Hospital. Hormonal markers of bone metabolism, lipid profiles, uric acid, glycosylated hemoglobin A1c (HbA1c), and beta-cell function were measured using blood samples. BMD was measured at the lumbar spine, femoral neck, and right hip by dual-energy X-ray absorptiometry. RESULTS: The mean BMD values from all three skeletal sites in male patients with LADA were comparable to those with classical T1DM but were much lower than those with T2DM. After adjusting for confounding factors, multiple linear regression analysis demonstrated that in all male patients with diabetes, body mass index (BMI), uric acid, and fasting C-peptide showed significant positive associations with BMD at all three skeletal sites; however, osteocalcin showed a negative association at all three sites. CONCLUSIONS: Compared with male patients with T2DM, lower BMDs were observed in patients with LADA and T1DM. Low BMI, uric acid, C-peptide levels, and high osteocalcin levels are risk factors for developing low BMD in male patients with diabetes.

[Low-level viremia-induced liver fibrosis and hepatocellular carcinoma in chronic hepatitis B].

Low-level viremia after antiviral therapy has gradually attracted attention due to its relation to liver fibrosis progression, hepatocellular carcinoma occurrence and long-term survival rate reduction in patients with chronic hepatitis B. In addition, it should be used as a risk factor for intervention during antiviral therapy in order to achieve complete virological response and improve the long-term prognosis of patients.

[A 2020 update on the progress of treatment and new drug clinical trials for hepatitis B].

Long term antiviral therapy with nucleos(ti)ide analogues could suppress HBV viral load thereby prevent the progression to cirrhosis and hepatocellular carcinoma. Interferon-based therapy could result in sustained virological response in a fair proportion of patients and even HBsAg loss in a small proportion of them. Novel therapies aiming at functional cure (loss of HBsAg) are under active development. Among the categories of many, HBV core protein inhibitors are safe and could suppress the HBV DNA and HBV RNA, but only with modest effect on the level of HBsAg; silencing of HBV mRNA by siRNA or antisense oligonucleotides could produce meaningful and sustainable declining in HBsAg levels; immune modulators with different mode of action showed modest effect on the reduction of HBsAg, but with noticeable adverse event (especially transaminase flares) related to the mode of action. Novel clinical trial design on the combination or sequential use of innovative molecules will ultimately lead to the functional cure of CHB in the near future.

Regulation of DGKε Activity and Substrate Acyl Chain Specificity by Negatively Charged Phospholipids.

Diacylglycerol kinase ε (DGKε) is a membrane-bound enzyme that catalyzes the ATP-dependent phosphorylation of diacylglycerol to form phosphatidic acid (PA) in the phosphatidylinositol cycle. DGKε lacks a putative regulatory domain and has recently been reported to be regulated by highly curved membranes. To further study the effect of other membrane properties as a regulatory mechanism of DGKε, our work reports the effect of negatively charged phospholipids on DGKε activity and substrate acyl chain specificity. These studies were conducted using purified DGKε and detergent-free phospholipid aggregates, which present a more suitable model system to access the impact of membrane physical properties on membrane-active enzymes. The structural properties of the different model membranes were studied by means of differential scanning calorimetry and 31P-NMR. It is shown that the enzyme is inhibited by a variety of negatively charged phospholipids. However, PA, which is a negatively charged phospholipid and the product of DGKε catalyzed reaction, showed a varied regulatory effect on the enzyme from being an activator to an inhibitor. The type of feedback regulation of DGKε by PA depends on the particular PA molecular species as well as the physical properties of the membrane that the enzyme binds to. In the presence of highly packed PA-rich domains, the enzyme is activated. However, its acyl chain specificity is only observed in liposomes containing 1,2-dioleoyl PA in the presence of Ca2+. It is proposed that to endow the enzyme with its substrate acyl chain specificity, a highly dehydrated (hydrophobic) membrane interface is needed. The presence of an overlap of mechanisms to regulate DGKε ensures proper phosphatidylinositol cycle function regardless of the trigged stimulus and represents a sophisticated and specialized manner of membrane-enzyme regulation.