Expression, purification and characterization of CTP synthase PyrG in Staphylococcusaureus.

Staphylococcus aureus (S. aureus) presents a significant challenge in both nosocomial and community settings due to its pathogenicity. The emergence of drug-resistant strains exacerbates S. aureus infections, leading to increased mortality rates. PyrG, a member of the cytidine triphosphate (CTP) synthase family, serves as a crucial therapeutic target against S. aureus due to the pivotal role of CTP in cellular metabolism. However, the structural and mechanistic details of S. aureus PyrG remains unknown. Here, we successfully expressed and purified monomeric PyrG. Mutational experiments were conducted based on the results of molecular docking. Based on the results of the molecular docking, we carried out mutation experiments and found that Q386A dramatically decreased the CTP synthase activity compared to the wild-type protein, while Y54A almost completely abolished the activity. Exposure of S. aureus to the kinase inhibitor crizotinib increased expression of gene pyrG. Our results identify the two key sites on PyrG for the CTP synthase activity, and present PyrG gene expression increased during the treatment of crizotinib, which may eventually provide valuable guidance for the development of new drugs against S. aureus infections.

Characteristics and Differences in Mpox Patients with and without HIV Infection: A Retrospective Cross-Sectional Study in Chengdu, China.

Purpose: To date, there are few reports about mpox case series in China, and scarce information is available about the in-vivo kinetics of T-cell responses in the early stage of mpox infection. This study aims to investigate the clinical difference among mpox patients with and without human immunodeficiency virus (HIV) infection. Patients and Methods: A total of 56 patients diagnosed with mpox by Chengdu Center for Disease Control and Prevention (CDC) and hospitalized in Public Health Clinical Center of Chengdu were retrospectively included and divided into an HIV-infected group (n=23) and a non-HIV-infected group (n=33). Clinical characteristics and serum chemistry findings of mpox patients were collected in order to analyze the differences between the HIV-infected group and the non-HIV-infected group. Results: Multiple laboratory abnormalities, including elevated C-reactive protein (69.1%), hypocalcemia (50.9%), elevated CD3+CD8+T counts (47.0%) and inverted ratio of CD3+CD4+T to CD3+CD8+T (64.7%) were common in mpox cases. There were statistically significant differences (all P < 0.05) in age, serum calcium levels, CD3+CD4+T counts, the ratio of CD3+CD4+T to CD3+CD8+T, proportion with >10 rashes, incidence of proctitis anus and time from rash growth to rash scab shedding between HIV-infected group and non-HIV-infected group. In the early stage of mpox infection, the median of CD3+CD8+T counts in the non-HIV-infected group was significantly higher than that in healthy donors (P<0.001), and the median of CD3+CD4+T/CD3+CD8+T ratio was significantly lower (P<0.001). The median of CD3+CD4+T counts in mpox patients co-infected with HIV significantly decreased compared to the pre-infection level (p =0.033). Conclusion: Our study indicates that mpox co-infected with HIV patients have longer lasting rash lesions and a higher incidence of proctitis anus. T-cell responses may be different between HIV-infected and non-HIV-infected individuals in the early stage of mpox infection.

Impact of diabetes itself and glycemic control status on tuberculosis.

Objectives: To explore the impact of diabetes itself and glycemic control status on tuberculosis (TB). Methods: A total of 3393 patients with TB and diabetes mellitus (DM) who were hospitalized in the Public Health Clinical Center of Chengdu from January 1, 2019, to December 31, 2021, were retrospectively included and divided into three groups according to baseline glycemic control status: two groups according to glycemic status at discharge, two groups according to cavity occurrence, three groups according to sputum results, and three groups according to lesion location. The influencing factors and the differences in cavity occurrence, sputum positivity and lesion location among different glycemic control groups or between different glycemic status groups were analyzed. Results: In this TB with DM cohort, most of the subjects were male, with a male to female ratio of 4.54:1, most of them were 45-59 years old, with an average age of 57.44 ± 13.22 years old. Among them, 16.8% (569/3393) had cavities, 52.2% (1770/3393) were sputum positive, 30.4% (1030/3393) had simple intrapulmonary lesions, 68.1% (2311/3393) had both intra and extrapulmonary lesions, only 15.8% (537/3393) had good glycemic control,16.0% (542/3393) and 68.2% (2314/3393) had fair and poor glycemic control, respectively. Compared with the non-cavity group, the sputum-negative group and the extrapulmonary lesion group, the cavity group, sputum-positive group, intrapulmonary lesion group and the intra and extrapulmonary lesion group all had higher fasting plasma glucose (FPG) and glycosylated hemoglobin A 1c (HbA1c) and lower good glycemic control rates at admission (all P<0.001). Another aspect, compared with the good glycemic control group, the poor glycemic control group had a higher cavity occurrence rate, sputum positive rate, and greater proportion of intrapulmonary lesions. Moreover, FPG and HbA1c levels and poor glycemic control were significantly positively correlated with cavity occurrence, sputum positivity, and intrapulmonary lesions and were the main risk factors for TB disease progression. On the other hand, cavity occurrence, sputum positivity, and intrapulmonary lesions were also main risk factors for hyperglycemia and poor glycemic control. Conclusion: Diabetes itself and glycemic control status could impact TB disease. Good glycemic control throughout the whole process is necessary for patients with TB and DM to reduce cavity occurrence and promote sputum negative conversion and lesion absorption.

How immune breakthroughs could slow disease progression and improve prognosis in COVID-19 patients: a retrospective study.

Background: Previous infections and vaccinations have produced preexisting immunity, which differs from primary infection in the organism immune response and may lead to different disease severities and prognoses when reinfected. Objectives: The purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19. Methods: A retrospective cohort study was conducted on 1513 COVID-19 patients in Chengdu Public Health Clinical Medical Center from January 2020 to November 2022. All patients were divided into the no immunity group (primary infection and unvaccinated, n=1102) and the immune breakthrough group (previous infection or vaccination, n=411). The immune breakthrough group was further divided into the natural immunity subgroup (n=73), the acquired immunity subgroup (n=322) and the mixed immunity subgroup (n=16). The differences in clinical and outcome data and T lymphocyte subsets and antibody levels between two groups or between three subgroups were compared by ANOVA, t test and chi-square test, and the relationship between T lymphocyte subsets and antibody levels and the disease progression and prognosis of COVID-19 patients was assessed by univariate analysis and logistic regression analysis. Results: The total critical rate and the total mortality rate were 2.11% and 0.53%, respectively. The immune breakthrough rate was 27.16%. In the no immunity group, the critical rate and the mortality rate were all higher, and the coronavirus negative conversion time was longer than those in the immune breakthrough group. The differences in the critical rate and the coronavirus negative conversion time between the two groups were all statistically significant (3.72% vs. 0.24%, 14.17 vs. 11.90 days, all p<0.001). In addition, in the no immunity group, although lymphocyte counts and T subsets at admission were higher, all of them decreased consistently and significantly and were significantly lower than those in the immune breakthrough group at the same time from the first week to the fourth week after admission (all p<0.01). The total antibody levels and specific Immunoglobulin G (IgG) levels increased gradually and were always significantly lower than those in the immune breakthrough group at the same time from admission to the fourth week after admission (all p<0.001). Moreover, in the natural immunity subgroup, lymphocyte counts and T subsets at admission were the highest, and total antibody levels and specific IgG levels at admission were the lowest. Then, all of them decreased significantly and were the lowest among the three subgroups at the same time from admission to one month after admission (total antibody: from 546.07 to 158.89, IgG: from 6.00 to 3.95) (all p<0.001). Those in the mixed immunity subgroup were followed by those in the acquired immunity subgroup. While lymphocyte counts and T subsets in these two subgroups and total antibody levels (from 830.84 to 1008.21) and specific IgG levels (from 6.23 to 7.51) in the acquired immunity subgroup increased gradually, total antibody levels (from 1100.82 to 908.58) and specific IgG levels (from 7.14 to 6.58) in the mixed immunity subgroup decreased gradually. Furthermore, T lymphocyte subsets and antibody levels were negatively related to disease severity, prognosis and coronavirus negative conversion time. The total antibody, specific IgM and IgG levels showed good utility for predicting critical COVID-19 patients and dead COVID-19 patients. Conclusion: Among patients with COVID-19 patients, immune breakthroughs resulting from previous infection or vaccination, could decelerate disease progression and enhance prognosis by expediting host cellular and humoral immunity to accelerate virus clearance, especially in individuals who have been vaccinated and previously infected. Clinical trial registry: Chinese Clinical Trial Register ChiCTR2000034563.

Structural and Functional Insights into the Stealth Protein CpsY of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is an important and harmful intracellular pathogen that is responsible for the cause of tuberculosis (TB). Mtb capsular polysaccharides can misdirect the host's immune response pathways, resulting in additional challenges in TB treatment. These capsule polysaccharides are biosynthesized by stealth proteins, including CpsY. The structure and functional mechanism of Mtb CpsY are not completely delineated. Here, we reported the crystal structure of CpsY201-520 at 1.64 Å. CpsY201-520 comprises three ß-sheets with five α-helices on one side and three on the other. Four conserved regions (CR1-CR4) are located near and at the base of its catalytic cavity, and three spacer segments (S1-S3) surround the catalytic cavity. Site-directed mutagenesis demonstrated the strict conservation of R419 at CR3 and S1-S3 in regulating the phosphotransferase activity of CpsY201-520. In addition, deletion of S2 or S3 (∆S2 or ∆S3) dramatically increased the activity compared to the wild-type (WT) CpsY201-520. Results from molecular dynamics (MD) simulations showed that S2 and S3 are highly flexible. Our study provides new insights for the development of new vaccines and targeted immunotherapy against Mtb.

Monomer and Oligomer Transition of Zinc Phthalocyanine Is Key for Photobleaching in Photodynamic Therapy.

Photodynamic therapy (PDT) is recognized as a powerful method to inactivate cells. However, the photosensitizer (PS), a key component of PDT, has suffered from undesired photobleaching. Photobleaching reduces reactive oxygen species (ROS) yields, leading to the compromise of and even the loss of the photodynamic effect of the PS. Therefore, much effort has been devoted to minimizing photobleaching in order to ensure that there is no loss of photodynamic efficacy. Here, we report that a type of PS aggregate showed neither photobleaching nor photodynamic action. Upon direct contact with bacteria, the PS aggregate was found to fall apart into PS monomers and thus possessed photodynamic inactivation against bacteria. Interestingly, the disassembly of the bound PS aggregate in the presence of bacteria was intensified by illumination, generating more PS monomers and leading to an enhanced antibacterial photodynamic effect. This demonstrated that on a bacterial surface, the PS aggregate photo-inactivated bacteria via PS monomer during irradiation, where the photodynamic efficiency was retained without photobleaching. Further mechanistic studies showed that PS monomers disrupted bacterial membranes and affected the expression of genes related to cell wall synthesis, bacterial membrane integrity, and oxidative stress. The results obtained here are applicable to other types of PSs in PDT.

Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in patients with COVID-19.

Background: Organism can lead to excessive nutrient consumption in the infected state and increase nutritional risk, which is detrimental to the control of the infection and can further aggravate the disease. Objectives: To investigate the impact of nutritional risk and the NRS2002 score on disease progression and prognosis in patients with COVID-19. Methods: This was a retrospective cohort study including 1,228 COVID-19 patients, who were divided into a with-nutritional risk group (patients with NRS2002 score ≥ 3) and a without-nutritional risk group (patients with NRS2002 score < 3) according to the NRS2002 score at admission. The differences in clinical and outcome data between the two groups were compared, and the relationship between the NRS2002 score and the disease progression and prognosis of COVID-19 patients was assessed. Results: Of 1,228 COVID-19 patients, including 44 critical illness patients and 1,184 non-critical illness patients, the rate of harboring nutritional risk was 7.90%. Compared with those in the without-nutritional risk group, patients in the with-nutritional risk group had a significantly longer coronavirus negative conversion time, significantly lower serum albumin (ALB), total serum protein (TP) and hemoglobin (HGB) at admission, discharge or 2 weeks, a significantly greater proportion with 3 or more comorbidities, and a significantly higher rate of critical illness and mortality (all p < 0.001). Multiple regression analysis showed that nutritional risk, NRS2002 score and ALB at admission were risk factors for disease severity. In addition, nutritional risk, NRS2002 score and TP at admission were risk factors for prognosis. The NRS2002 score showed the best utility for predicting critical illness and death in COVID-19 patients. Conclusion: Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in COVID-19 patients. For patients with NRS2002 score > 0.5, early intervention of malnutrition is needed to reduce the occurrence of critical disease. Additionally, for patients with NRS2002 score > 5.5, continuous nutritional support therapy is needs to reduce mortality and improve prognosis.Clinical Trial registration: [https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2000034563], identifier [Chinese Clinical Trial Register ChiCTR2000034563].

Glucose metabolism continuous deteriorating in male patients with human immunodeficiency virus accepted antiretroviral therapy for 156 weeks.

BACKGROUND: The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus (PLWH) who accepted primary treatment with the efavirenz (EFV) plus lamivudine (3TC) plus tenofovir (TDF) (EFV + 3TC + TDF) regimen are unclear and warrant investigation. AIM: To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV + 3TC + TDF regimen for 156 wk. METHODS: This study was designed using a follow-up design. Sixty-one male treatment-naive PLWH, including 50 cases with normal glucose tolerance and 11 cases with prediabetes, were treated with the EFV + 3TC + TDF regimen for 156 wk. The glucose metabolism dynamic characteristics, the main risk factors and the differences among the three CD4+ count groups were analyzed. RESULTS: In treatment-naive male PLWH, regardless of whether glucose metabolism disorder was present at baseline, who accepted treatment with the EFV + 3TC + TDF regimen for 156 wk, a continuous increase in the fasting plasma glucose (FPG) level, the rate of impaired fasting glucose (IFG) and the glycosylated hemoglobin (HbA1c) level were found. These changes were not due to insulin resistance but rather to significantly reduced islet ß cell function, according to the homeostasis model assessment of ß cell function (HOMA-ß). Moreover, the lower the baseline CD4+ T-cell count was, the higher the FPG level and the lower the HOMA-ß value. Furthermore, the main risk factors for the FPG levels were the CD3+CD8+ cell count and viral load (VL), and the factors contributing to the HOMA-ß values were the alanine aminotransferase level, VL and CD3+CD8+ cell count. CONCLUSION: These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased islet ß cell function during antiretroviral therapy with the EFV + 3TC + TDF regimen for long-term application.

High Number and Specific Comorbidities Could Impact the Immune Response in COVID-19 Patients.

Background: Cellular immunodeficiency and comorbidities are common in COVID-19 patients. Aim: The purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients. Methods: The research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated. Results: Compared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P<0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P<0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively. Conclusions: High numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients. Clinical Trial Registry: https://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.

Follow-Up Study of the Cardiopulmonary and Psychological Outcomes of COVID-19 Survivors Six Months After Discharge in Sichuan, China.

PURPOSE: Some studies have shown that patients with coronavirus disease 2019 (COVID-19) still have sequelae after discharge. However, little is known about the long-term physical and psychological sequelae of patients, especially factors that influenced the prognosis. PATIENTS AND METHODS: Patients with COVID-19 were followed up for 6 months. The psychological status of patients was evaluated by DASS-21 questionnaire, while physical functions were determined using medical history, laboratory examination, thoracic computed tomography (CT), and echocardiography. RESULTS: Fifty patients infected with COVID-19 were enrolled, and 11 (22%) patients still showed symptoms related to COVID-19. The mean contents (cells/ul) of CD3+ cells, CD4+ and CD8+ T, B lymphocytes and NK cells of the survivors elevated significantly after 6-month discharge (P < 0.001). The frequency of ground-glass opacities and consolidations decreased from 90% to 42% (P < 0.001), and 54% to 20%, (P = 0.001), respectively, while the changes of reticulation and bronchiectasis were insignificant (P > 0.05). The frequency of left ventricular diastolic dysfunction decreased from 40% to 15% (P = 0.002). Depression was observed in 5 (12.5%) participants, stress in 3 (7.5%), anxiety in 6 (15%), and among them 1 (2.5%) showed extremely severe anxiety. Covariation analysis elucidated age might be a risk factor (OR: 1.09, 95% CI: 1.01-1.18, P = 0.038), while NK cell was a good prognostic factor for pulmonary recovery. The comorbidities were significantly positive correlated with persist pulmonary damage (r = 0.33, P = 0.020). Compared with patients with antiviral therapy, patients without antiviral therapy had higher anxiety score (3 vs 0, P = 0.033). CONCLUSION: After 6-month discharge, the persisting cardiopulmonary damage was observed in recovery patients, and psychological implications should not be ignored. Age, comorbidities, NK cell and antiviral therapy might be associated with the prognosis of COVID-19.

Gradual increasing dyslipidemia in treatment-naive male patients with human immunodeficiency virus and treated with tenofovir plus lamivudine plus efavirenz for 3 years.

INTRODUCTION: Since the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric acid monitoring. METHODS: A prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with human immunodeficiency virus (HIV) were divided into three groups based on their baseline CD4+ cell count (26, 12, and 23 patients in the < 200, 200 to 350, and > 350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed. RESULT: Within 144 weeks, TG, LDL-c, TC and HDL-c gradually increased, especially TC and HDL-c (P = 0.001, 0.000, respectively). Moreover, the percentages of hyper-cholesterolemia, hyper LDL cholesterolemia, hyper-triglyceridemia and low HDL cholesterolemia also gradually increased, especially low HDL cholesterolemia significantly increased (P = 0.0007). The lower the baseline CD4+ cell counts were, the higher the TG levels and the lower the TC, LDL-c and HDL-c levels were. But there was significant difference of only baseline LDL-c levels between the three groups (P = 0.0457). No significant difference of the UA level and the percentages of hyperuricemia was found between the different follow-up time point groups or between the three CD4+ cell counts groups (all P > 0.05). The risk factors for dyslipidemia included age, anthropometric parameters and follow-up weeks, and for hyperuricemia was virus load. CONCLUSIONS: Gradual increasing dyslipidemia was found in male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz for 3 years. There-fore lipid metabolism parameters should be closely monitored during long-term ART with the TDF plus 3TC plus EFV regimen.

Significantly Decreased Islet ß Cell Function is Closely Associated with Hyperglycemia in Chronic Hepatitis B Patients.

AIM: This study is aimed at the characteristics of glucose metabolism and islet ß cell function evaluated by the homeostasis model assessment of ß cell function (HOMA-ß) value and its risk factors in chronic hepatitis B (CHB) patients. METHOD: This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index under the same glucose metabolism status. The risk factors, characteristics, and differences in glucose metabolism and HOMA-ß values between the two groups were analyzed. RESULTS: The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) or hepatitis B envelope antigen (HBeAg) (-) status. In addition, under the same glucose metabolism status, the fasting plasma glucose (FPG) levels and 2-hour postprandial plasma glucose (2h-PG) levels in the CHB group were higher, while the HOMA-ß values were significantly lower and the homeostasis model assessment of insulin resistance (HOMA-IR) value was not higher than that in the non-HBV group (all P < 0.0001). Further analyses revealed that the main risk factors for abnormal glucose metabolism were HBeAg (-) status and hepatitis B envelope antibody levels. But HBV serological and virological indicators had no effects on the HOMA-ß values. CONCLUSION: Islet ß cell function in patients with CHB was compromised, which is closely associated with fasting and postprandial hyperglycemia in chronic hepatitis B patients. Further research should be done to verify the compromised islet ß cell function and then to investigate the mechanisms behind the effect of hepatitis B virus infection on islet ß cell function in CHB patients.

Overall reduced lymphocyte especially T and B subsets closely related to the poor prognosis and the disease severity in severe patients with COVID-19 and diabetes mellitus.

BACKGROUND: A dysregulated host immune response is common in patients with COVID-19. AIM: In this study, we aimed to define the characteristics of lymphocyte subsets and their relationship with disease progression in COVID-19 patients with or without diabetes mellitus (DM). METHODS: The baseline peripheral lymphocyte subsets were compared between 55 healthy controls and 95 patients with confirmed COVID-19, and between severe and non-severe COVID-19 patients with or without DM. RESULTS: The prevalence of DM in the COVID-19 group was 20%, and patients with severe COVID-19 had a higher prevalence of DM than those with non-severe disease (P = 0.006). Moreover, a significantly poor prognosis and a higher rate of severity were found in those with DM relative to those without DM (P = 0.001, 0.003). Generally, all lymphocytes and subsets of lymphocytes, especially B and T cells, were significant reduced in COVID-19 patients, particularly in those with DM. Patients with severe COVID-19 and DM had the lowest lymphocyte counts compared with those with severe COVID-19 without DM, and those with non-severe COVID-19 with or without DM. Partially decreased lymphocyte subsets, age and DM were closely related to disease progression and prognosis. CONCLUSIONS: These findings provide a reference for clinicians that immunomodulatory treatment may improve disease progression and prognosis of COVID-19 patients, especially those with severe disease with DM. Trial registration Chinese Clinical Trial Register ChiCTR2000034563.

Not Only High Number and Specific Comorbidities but Also Age Are Closely Related to Progression and Poor Prognosis in Patients With COVID-19.

Background: Some patients with comorbidities and rapid disease progression have a poor prognosis. Aim: We aimed to investigate the characteristics of comorbidities and their relationship with disease progression and outcomes of COVID-19 patients. Methods: A total of 718 COVID-19 patients were divided into five clinical type groups and eight age-interval groups. The characteristics of comorbidities were compared between the different clinical type groups and between the different age-interval groups, and their relationships with disease progression and outcomes of COVID-19 patients were assessed. Results: Approximately 91.23% (655/718) of COVID-19 patients were younger than 60 years old. Approximately 64.76% (465/718) had one or more comorbidities, and common comorbidities included non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes mellitus (DM), chronic hepatitis B (CHB), hyperuricaemia, and gout. COVID-19 patients with comorbidities were older, especially those with chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Hypertension, DM, COPD, chronic kidney disease (CKD) and CVD were mainly found in severe COVID-19 patients. According to spearman correlation analysis the number of comorbidities was correlated positively with disease severity, the number of comorbidities and NAFLD were correlated positively with virus negative conversion time, hypertension, CKD and CVD were primarily associated with those who died, and the above-mentioned correlation existed independently of age. Risk factors included age, the number of comorbidities and hyperlipidaemia for disease severity, the number of comorbidities, hyperlipidaemia, NAFLD and COPD for the virus negative conversion time, and the number of comorbidities and CKD for prognosis. Number of comorbidities and age played a predictive role in disease progression and outcomes. Conclusion: Not only high number and specific comorbidities but also age are closely related to progression and poor prognosis in patients with COVID-19. These findings provide a reference for clinicians to focus on not only the number and specific comorbidities but also age in COVID-19 patients to predict disease progression and prognosis. Clinical Trial Registry: Chinese Clinical Trial Register ChiCTR2000034563.

Lymphocyte subsets with the lowest decline at baseline and the slow lowest rise during recovery in COVID-19 critical illness patients with diabetes mellitus.

BACKGROUND: Host dysregulation of immune response was highly involved in the pathological process of Coronavirus disease 2019 (COVID-19), especially COVID-19 severe cases with DM. AIM: In this study we aimed at the dynamic change of peripheral lymphocyte and subsets during COVID-19 covery. METHODS: The peripheral lymphocyte and subsets of 95 confirmed cases with COVID-19 from baseline to four weeks were compared between critical illness and non-critical illness cases with or without DM. RESULTS: The dynamic characteristics of lymphocyte and subsets in COVID-19 patients was that it reduced significantly at one week, rapidly elevated to the peak at two weeks after onset, then gradually declined during recovery. The COVID-19 critical illness patients with DM had the lowest decline at one week and the slow lowest rise at two weeks after onset, while COVID-19 non-critical illness patients with DM had the rapid highest rise at two weeks after onset, both of them had similar lymphocyte and subsets at five weeks after onset and lower than those patients without DM. CONCLUSIONS: These findings provide a reference for clinicians that for COVID-19 patients with DM and the lowest decline of lymphocyte and subsets, immunomodulatory therapy as soon as possible might avoid or slow down disease progression; moreover for COVID-19 critical illness patients with or without DM and non-critical illness patients with DM, continuous immunomodulatory therapy in later stages of disease might speed up virus clearance, shorten hospital stay, improve disease prognosis in COVID-19 critical illness patients with DM.

[Difference of Liver Enzymes in Different Metabolism States of Chronic Hepatitis B].

OBJECTIVE: To analyze the difference of liver enzymes in different metabolism state groups of chronic hepatitis B (CHB). METHODS: We use prospective cross-sectional study to analyze the difference of liver enzymes in different metabolism state groups in 110 cases of CHB, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl transferase (GGT). RESULTS: Regardless of the presence or absence of fatty liver, the levels of ALP and GGT were increased along with the deterioration of glucose metabolism (P<0.05).The levels of ALP and GGT in the presence of fatty liver group were higher than those in the absence of fatty liver group (P<0.05). The levels of AST, ALP and GGT showed the trend of increasing along with the increase of HOMA-IR and the decrease of HOMA-ß. There was no difference of liver enzymes among the groups with or without other metabolism disorder (P>0.05). CONCLUSION: In CHB, abnormal glucose metabolism and fatty liver can lead to the increase of ALP and GGT. The increase of HOMA-IR and the decrease of HOMA-ß may lead to the increase of AST, ALP and GGT. Other metabolism disorder did not show any effect on the level of liver enzymes.

[Predicting visceral and abdominal subcutaneous adipose areas with anthropometric parameters in Chinese male patients with type 2 diabetes].

OBJECTIVE: To predict the abdominal subcutaneous adipose area (SA) and visceral adipose area (VA) with simple anthropometric parameters in Chinese male patients with type 2 diabetes. METHODS: The SA and VA were measured by Computed Tomography (CT) in 91 Chinese male patients with type 2 diabetes. The anthropometric parameters used in predicting the SA and VA included weight (W), height (H), body mass index (BMI), waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR). The multiple stepwise regression analysis was undertaken in a randomly selected sample with 77 subjects (80% of total subjects) to establish predictive equations between the SA or VA and the anthropometric parameters. The equations were then cross-validated in the remaining 14 subjects (20% of total subjects) that had not been included in the regression analysis. RESULTS: The BMI and WC entered into the final predictive equation for the SA, while the BMI remained to be the only variable for predicting the SA. The differences between the predicted values and the observed values were 2.06% and 4.34% for the VA and SA respectively. CONCLUSION: The VA and SA in Chinese male patients with type 2 diabetes can be well predicted by anthropometric measurements.