ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization.

Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.

Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection.

BACKGROUND AND AIMS: We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. METHODS: In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. RESULTS: A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. CONCLUSION: This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.

Ozone exposure associates with sperm quality indicators: Sperm telomere length as a potential mediating factor.

Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 µg/m3 increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis.

BACKGROUND: Only a few cases of chronic hepatitis B (CHB) with primary biliary cholangitis (PBC) have been reported based on histological evidence from liver biopsies. AIM: To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC. METHODS: Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital, affiliated with Jiangsu University, and Wuxi Fifth People's Hospital, from January 2005 to September 2020, were selected. All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC. RESULTS: Only five had elevated alkaline phosphatase levels, nine were positive for anti-mitochondrial antibody (AMA)-M2, and two were negative for AMA-M2. Two had jaundice and pruritus symptoms, 10 had mildly abnormal liver function, and one had severely elevated bilirubin and liver enzyme levels. The pathological characteristics of CHB complicated by PBC overlapped with those of PBC-autoimmune hepatitis (AIH). When necroinflammation of the portal area is not obvious, the pathological features of PBC are predominant, similar to the features of PBC alone. When the interface is severe, biliangitis will occur, with a large number of ductular reactions in zone 3. Unlike the PBC-AIH overlap pathology, this pathology is characterized by a small amount of plasma cell infiltration. Unlike PBC, lobulitis is often observed. CONCLUSION: This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

TCS01 Two-Component System Influenced the Virulence of Streptococcus pneumoniae by Regulating PcpA.

Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.

Successful treatment of invasive liver abscess syndrome caused by Klebsiella variicola with intracranial infection and septic shock: A case report.

BACKGROUND: Klebsiella variicola (K. variicola) is a member of the Klebsiella genus and is often misidentified as Klebsiella pneumoniae. In this report, we present a rare case of invasive liver abscess caused by K. variicola. CASE SUMMARY: We report a rare case of liver abscess due to K. variicola. A 57-year-old female patient presented with back pain for a month. She developed a high-grade fever associated with chills, and went into a coma and developed shock. The clinical examinations and tests after admission confirmed a diagnosis of primary liver abscess caused by K. variicola complicated by intracranial infection and septic shock. The patient successfully recovered following early percutaneous drainage of the abscess, prompt appropriate antibiotic administration, and timely open surgical drainage. CONCLUSION: This is a case of successful treatment of invasive liver abscess syndrome caused by K. variicola, which has rarely been reported. The findings of this report point to the need for further study of this disease.

Multiple immune function impairments in diabetic patients and their effects on COVID-19.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.

Nitroglycerin ameliorates liver injury and regulates adaptive immunity in mice.

This study aimed to assess the protective effect of nitroglycerin, a commonly used drug in cardiovascular diseases, on mice with acute liver injury induced by carbon tetrachloride (CCl4 ). The mice were randomly divided into three groups: control, CCl4 , and CCl4 + nitroglycerin. They were killed at 0, 6, 12, 24, and 48 h after treatment. Blood and liver tissue samples were collected for analysis. Analysis of the amounts of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hepatic glutathione (GSH), and malondialdehyde (MDA) showed that nitroglycerin protected against CCl4 -induced acute liver injury. Liver histological analysis provided further evidence of the protective effect of nitroglycerin. Furthermore, we found that nitroglycerin suppressed the increase of T helper 17 (Th17) cells in CCl4 -induced acute liver injury mice. The results indicate that nitroglycerin is a potential candidate for hepatic disease.

Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. METHODS: PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7-10-day, 28-30-day and 90-180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger's and Begger's test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). RESULTS: Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93-1.12), p = 0.65]. Subgroup analysis revealed no difference of 7-10-day mortality [RR(95%CI)) = 0.89(0.54-1.49), p = 0.66], 28-30-day mortality[RR(95%CI) = 1.00(0.89-1.12), p = 0.98] and 90-180-day mortality [RR(95%CI) = 1.11(0.94-1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(- 0.12-0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.

Ductopenia and cirrhosis in a 32-year-old woman with progressive familial intrahepatic cholestasis type 3: A case report and review of the literature.

Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitive diagnosis of familial intrahepatic cholestasis type 3. Her symptoms and liver function improved after 3 mo of treatment with ursodeoxycholic acid.

LincRNA-p21 promotes mesenchymal stem cell migration capacity and survival through hypoxic preconditioning.

BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow have potent stabilizing effects for the treatment of acute respiratory distress syndrome (ARDS). However, low efficiency and survival in MSC homing to injured lung tissue remains to be solved. Therefore, the aim of this study was to assess whether large intergenic noncoding RNA (LincRNA)-p21 promote MSC migration and survival capacity through hypoxic preconditioning in vitro. METHODS: MSCs were cultured and divided into the normoxia culture group (20% O2) and hypoxia culture group (1% O2). To determine roles and mechanisms, lentivirus vector-mediated LincRNA-p21 knockdown of MSCs and hypoxia-inducible factor (HIF-1α) inhibitor KC7F2 were introduced. Additionally, MSC migration was analyzed by scratch test and transwell migration assays. MSC proliferation was tested by cell counting kit-8 and trypan blue dye. Apoptosis was detected by Annexin V-PE/7-AAD stained flow cytometry. Moreover, LincRNA-p21 and HIF-1α mRNA was measured by reverse transcription-polymerase chain reaction, and HIF-1α and CXCR4/7 protein were assayed by western blot (WB) or enzyme-linked immunosorbent assay (ELISA). Apoptosis protein caspase-3 and cleaved-caspase-3 were investigated by WB analysis. Considering interactions between VHL and HIF-1α under LincRNA-p21 effect, co-immunoprecipitation was detected. RESULTS: Hypoxic preconditioning MSC promoted migration capacity and MSC survival than normoxia culture group. MSCs induced by hypoxic preconditioning evoked an increase in expression of LincRNA-p21, HIF-1α, and CXCR4/7(both were chemokine stromal-derived factor-1(SDF-1) receptors). Contrarily, blockade of LincRNA-p21 by shRNA and HIF-1α inhibitor KC7F2 abrogated upregulation of hypoxic preconditioning induced CXCR4/7 in MSCs, cell migration, and survival. Furthermore, co-immunoprecipitation assay revealed that hypoxic preconditioning isolated VHL and HIF-1α protein by increasing HIF-1α expression. CONCLUSIONS: Hypoxic preconditioning was identified as a promoting factor of MSC migration and survival capacity. LincRNA-p21 promotes MSC migration and survival capacity through HIF-1α/CXCR4 and CXCR7 pathway under hypoxic preconditioning in vitro.

Identification of a novel torque teno mini virus in cerebrospinal fluid from a child with encephalitis.

Anelloviruses are single-strand circular DNA viruses and ubiquitous within the human population. Although there is no direct evidence, many studies have suggested the anelloviruses may be associated with a variety of diseases. In this study, a novel torque teno mini virus (TTMV) was detected in a child with unexplained encephalitis. The detected virus had a circular genome of 2943 nt in length and 3 open reading frames. It shared 45.4% - 35.9% nucleotide identities with known TTMV species and < 35% with the other species of anellovirus, which suggested it might belong to a new species within the genus Betatorquevirus. Phylogenetic analysis based on the amino acid sequences of ORF1 showed that this virus represented a distinct branch within the diversity of anellovirus. Whether this novel anellovirus strain is associated with encephalitis requires further study.

The effects of fluid resuscitation according to PiCCO on the early stage of severe acute pancreatitis.

OBJECTIVES: To evaluate the therapeutic effect of early fluid resuscitation under the guidance of Pulse indicator Continuous Cardiac Output (PiCCO) on patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 18 SAP patients (the study group), who had undergone fluid resuscitation under the guidance of PiCCO from October 2011 to October 2013, were analyzed prospectively. Clinical data of 25 cases (control group) who had undergone fluid resuscitation without the guidance of PiCCO from January 2009 to September 2011 were collected. Then, retrospective and prospective case-control study was carried out. RESULTS: During the first 6 h, 0-24 h, 24-48 h, and 0-72 h of admission, the study group received more volume of fluid than the control group. There were significantly faster decline of APACHE II score and the value of blood lactate in study group, as well as the length of ICU stay and the proportion of renal failure at 72 h of admission. According to the 2012 Atlanta classification, six cases in study group turned into moderate SAP (33.30%), significantly higher than the control group (8.00%) (p = 0.0049). The volume of fluid infusion and clinical parameters were linearly relative. CONCLUSIONS: The PiCCO device may be a useful adjunct for fluid resuscitation monitoring in patients with SAP in the early stage. Early fluid resuscitation under the guidance of PiCCO can improve tissue perfusion, reduce the SIRS persistence time and the length of ICU stay. This program did not increase the risk of respiratory failure and influence the mortality.

Characterization of Full-Length Genomes of Hepatitis B Virus Quasispecies in Sera of Patients at Different Phases of Infection.

Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.

N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape.

BACKGROUND & AIMS: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. METHODS: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. RESULTS: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. CONCLUSIONS: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area.

T helper cell dysregulation with hepatitis B and rebalance with glucocorticoids.

AIM: To investigate T helper 17/regulatory T cell alterations in early severe hepatitis B and the effect of glucocorticoids. METHODS: The study included 20 patients in the early stage of severe hepatitis B (SHB) and 11 healthy controls. All patients had elevated T helper 17 (Th17) levels, decreased regulatory T (Treg) cell levels, and significant Th17/Treg ratios. RESULTS: After glucocorticoid treatment, 16 patients showed improvement with significant decreases in Th17 levels, increases in Treg, and rebalanced Th17/Treg ratios. The four patients who showed no improvement had increases in both Th17 and Treg levels and an even higher Th17/Treg ratio than before. CONCLUSION: Glucocorticoid treatment can rectify Th17/Treg dysregulation in patients with SHB.

[Relationship between serum HBV DNA level and follicular helper T lymphocyte in patients with chronic hepatitis B and its significance].

OBJECTIVE: To explore relationship between HBV DNA level and peripheral blood follicular helper T lymphocyte (Tfh) in patients with chronic hepatitis B (CHB) and its significance. METHODS: HBV DNA levels of 179 cases of CHB patients with positive HBV DNA, positive HBeAg and positive human leukocyte antigen(HLA)-A2 were tested with real time fluorescent quantitative PCR. Tfh and HBV specific CTL were tested with flow cytometry. IL-21 was also tested. 179 cases of CHB patients were divided into group A and group B based on HBV DNA levels, 86 cases in group A, HBV DNA levels were 10(4)-10(5) copies/ml, 93 cases in group B, HBV DNA levels were 10(6)-10(7) copies/ml. Above testing indexes of the two groups were compared. RESULTS: HBV DNA levels of group A were (4.85 +/- 0.37) log10 copies/ml, HBV DNA levels of group B were (6.83 +/- 0.31 ) log10 copies/ml, t = 27.31, P < 0. 001; Tfh of group A was (5.96 +/- 1.59)%, higher than that of group B (3.71 +/- 2.15)%, t = 4.92, P < 0.01; IL-21 of group A was (42.61 +/- 15.11)ng/L, higher than that of group B (14.91 +/- 3.15) ng/L, t = 8.62, P < 0.01; HBV specific CTL of group A was (0.36 +/- 0.08)%, higher than that of group B (0.18 +/- 0.06)%, t = 19.99, P < 0.001. CONCLUSION: Serum HBV DNA level of CHB patients is related to the level of peripheral blood Tfh level: patients with low HBV DNA level have high Tfh level, high IL-21 level and high HBV specific CTL level. Patients with high HBV DNA level have low Tfh level, low IL-21 level and low HBV specific CTL level. The mechanism of baseline HBV DNA level affecting anti-viral therapy may be related to Tfh level.

[Study on effects of kurarinol combined with glycyrrhizic acid on cellular immunity of patients with chronic hepatitis B].

OBJECTIVE: To explore effects of kurarinol combined with Diammonium Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis B (CHB). METHODS: Sixty-three CHB patients were randomly divided into two groups, 32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group (combined therapy group) were treated with 600 mg kurarinol glucose injection intravenously, once a day for one month, then 200 mg kurarinol capsule was used orally, three times a day for two months. 150 mg Diammonium Glycyrrhizinate for Injection was added to 250 ml 10% glucose injection for intravenous drip, once a day for one month, then 150 mg Diammonium Glycyrrhizinate capsule was used orally, three times a day for two months; 31 case in kurarinol group (single drug group) only used kurarinol, methods and dosage were the same as those of treatment group. HBV specific CTL, T cell subgroups, change of Th1 and Th2 level, HBV-DNA and HBeAg negative rate of the two groups were compared. RESULTS: Three months after treatment, HBV specific CTL, CD4 + and Th1 of combined therapy group were higher than those before treatment, and higher than those of single drug group after treatment (P < 0.01). CONCLUSION: HBV-DNA and HBeAg negative rate between the two groups had no statistic significance (P > 0.05). CONCLUSION: Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV specific CTL, CD4+ and Th1 level of CHB patients.

Effect of oxymatrine on specific cytotoxic T lymphocyte surface programmed death receptor-1 expression in patients with chronic hepatitis B.

BACKGROUND: Oxymatrine has certain antiviral effects in the treatment of chronic hepatitis B (CHB), but its exact mechanism is unclear. The objective of the present study was to explore oxymatrine's antiviral mechanism by studying its effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) expression in CHB patients. METHODS: Sixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg, positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x upper limit of normal value (ULN) were randomly divided into two groups: treatment group (n = 33), treated with an intravenous infusion of 600 mg oxymatrine in glucose solution once a day for a month, then with a 200 mg oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet three times a day; control group (n = 32) patients were treated only with silibin meglumine tablet, method and dosage were the same as those of treatment group. Three months later, peripheral blood HBV-specific CTL surface PD-1 expression, HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were analyzed and compared. RESULTS: Three months post-treatment, in the treatment group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 ± 15.94)%) decreased significantly compared to the pretreatment level ((31.30 ± 24.06)%; P < 0.05), and decreased significantly compared to that of control group three months after treatment ((29.45 ± 21.62)%; P < 0.05). HBV-specific CTL level ((0.42 ± 0.07)%) significantly increased compared with the pretreatment ((0.29 ± 0.15)%; P < 0.01), and the control group posttreatment level was (0.31 ± 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500 copies/ml, 33.33%), which was higher than that of the control group after treatment (two cases, 6.25%; χ(2) = 7.45, P < 0.01), HBeAg of nine cases turned negative (27.27%), which was higher than that of the control group after treatment (one case, 3.13%; χ(2) = 7.27, P < 0.01). CONCLUSION: Oxymatrine could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in CHB patients, increase HBV-specific CTL level, which may be one of the possible mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.