The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*

The outcome of hepatitis B virus (HBV) infection is determined by the complex interaction between the host's immune system and the virus and the proteins it produces, leading to the occurrence of acute and chronic liver diseases. In acute hepatitis B (AHB), the virus is cleared by the host through innate immunity and strong adaptive immunity. In chronic hepatitis B (CHB), both the innate and adaptive immunity of the host are continuously inhibited by HBV and the proteins it produces, which are not conducive to virus clearance. This article reviews the recent studies on innate immunity and adaptive immunity of acute and chronic viral hepatitis B, in order to provide ideas for further research and provide evidence for new clinical treatment method.

Objective:To summarize the clinical features and prognosis of acute kidney injury in patients with HBV related acute on chronic liver failure (ACLF).Methods:A total of 150 patients who developed acute kidney injury (AKI) in patients with HBV related ACLF from Sep. 2010 to Sep. 2019 were reviewed retrospectively, and the gender, age, laboratory examination, Child-pugh scores, and model for end-stage liver disease (MELD) were collected and the survival of the patients were followed up to analyze the prognosis.Results:Ninety-three percent of the patients were complicated with ascites, 81% with spontaneous peritonitis, 65% with hepatic encephalopathy and 58.7% with pulmonary infection; 60 patients (60.0%) were AKI stage 1, 44 patients (29.3%) were AKI stage 2, 16 patients (10.7%) were AKI stage 3. The patients with hyponatremia had lower albumin ( t=2.571, P=0.011), higher blood urea nitrogen, serum potassium and white blood cell levels than those without hyponatremia ( t=3.184, P=0.002; t=2.069, P=0.040; t=2.251, P=0.026); 74.7% of the patients died within 30 days, and the 90 days survival rate was 16.7%. The 30 days and 90 days mortality of patients with hyponatremia was higher than that of patients without hyponatremia ( χ2=4.11, P=0.044; χ2=3.901, P=0.049 7). Kaplan-Meier analysis revealed that the patients who had abnormal uric acid pre-diagnosis of AKI, hyponatremia when diagnosis of AKI, organ damage other than liver and kidney, metabolic acidosis, upper gastrointestinal tract bleeding, hepatic encephalopathy had a poor survival. Cox regression analysis showed that other organ function damage other than liver and kidney, metabolic acidosis, and the old age, were independent risk factors of death. Conclusions:Most of the AKI patients with HBV related ACLF had ascites and spontaneous bacterial peritonitis when AKI occurred, and AKI stage 1 was common. The mortality of patients with hyponatremia was high, and the risk of death was high in patients with severe organ damage other than liver and kidney, metabolic acidosis and the old age.

Objective Antiviral therapy should be adopted for chronic hepatitis B (CHB) patients with significant liver fibrosis to decrease the risk of liver related complications.Fibrosis assessment during antiviral treatment is a key step in antiviral therapy evaluation.Liver biopsy is the gold standard for assessing the degree of liver fibrosis.However,liver biopsy is difficult to perform more than one time after a long-term effective treatment because of the cost and risk of life-threatening complications.In this study we aimed to evaluate changes of liver fibrosis during 4 years of entecavir(ETV) treatment by non-invasive fibrosis markers in CHB patients who need antiviral therapy.Methods Totally 268 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy were performed before starting antiviral therapy in this study.Totally173 patients who needed antiviral therapy (liver fibrosis stages≥ F2,Metavir scoring system) were treated with ETV for at least 4 year.A clinical and virological evaluation was performed at baseline and again at 12,24,36 and 48 months during ETV treatment.Fibrosis-4 (FIB-4) index was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1,2,3 and 4 years of ETV treatment.Results Liver biopsy was performed for all enrolled patients at baseline.According to Metavir fibrosis stages,numbers of patients with FI,F2,F3 and F4 were 95,108,50 and 15,respectively.The FIB-4 index enabled the effective identification of patients with severe fibrosis (Metavir F3-F4) with an area under the ROC curve of 0.775 (95％CI 0.716-0.834).The FIB-4 values significantly decreased in F2 and F3 patients after 1 and 2 years ETV therapy (P＜0.01),respectively.But for F4 patients,FIB-4 values decreased significantly at year 4 (P＜0.05).Conclusions FIB-4 values decreased significantly during 4-year ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Objective:To investigate the association between the pathogenesis of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and the frequency and function of plasmacytoid dendritic cell (pDC) in patients HBeAg-positive chronic hepatitis B virus infection.Methods:A total of 49 HBeAg (+ ) patients with chronic hepatitis B virus infection in immune tolerance phase (IT) and 100 patients in immune clearance phase (IC) were enrolled. The viral serological indicators and liver function were detected. Peripheral venous blood samples were collected. The peripheral blood pDC frequency and the quantitative expression of co-stimulatory molecule CD86 were detected by flow cytometry, and the correlation between the onset of chronic hepatitis B and the frequency and function of pDC was analyzed.Results:In IC group, hepatitis B surface antigen (HBsAg) levels, HBeAg levels and hepatitis B virus (HBV) DNA loads were significantly lower than those in IT group, and alanine aminotransferase (ALT) levels in IC group were significantly higher than that in IT group; pDC% in IC group was significantly lower than that in IT group; CD86 + pDC% and CD86 mean fluorescentintensity (MFI) showed no significant difference between the two groups. In the IC group, the baseline pDC% was negatively correlated with ALT levels, while CD86 + pDC%, CD86MFI, and CD86 antibody binding capacity (ABC) had no remarkable correlation with ALT levels. Conclusions:The frequency of pDC was correlated with the pathogenesis of CHB. The lower the frequency of pDC in patients with CHB, the more prone to hepatitis. Therefore, increasing the frequency of pDC may inhibit the occurrence of hepatitis.

Objective: We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy. Methods: Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment. Results: All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05). Conclusions APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Objective: To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg positive chronic hepatitis B (CHB) patients. Method: HBeAg positive CHB patients treated with nucleoside analogue (NA) treatment received PEG-IFN α-2a 180 μg subcutaneously once weekly.NA was continually used with PEG-IFNα-2a during the first 12 weeks. HBsAg/HBeAg level and HBV DNA load were observed in the sequential pre-treatment (baseline) period, 12 th, 24 th, 36 th, 48 th and 72 nd weeks of sequential therapy in all patients. Result: Of the 56 HBeAg-positive CHB patients, 5 (23.1%) achieved HBsAg loss/seroconversion, the baseline HBsAg level in HBsAg loss/seroconversion group was lower than that of the patients in the group that did not achieve HBsAg loss/seroconversion (2.750 lg IU/ml vs. 3.699 lg IU/ml, t=0.955, P=0.000); the difference was statistically significant in HBsAg decreased at the 12 th, 24 th, 36 th, 48 th week in the course of sequential therapy (0.913 vs 0.149, 2.847 vs 0.189, 4.378 vs 0.248, 4.587 vs 0.274 lg IU/ml) (t=-2.950, P=0.040; t=-8.732, P=0.009; t=-8.483, P=0.001; t=-8.214, P=0.003); 11(19.6%) achieved HBeAg loss/ seroconversion, the HBeAg baseline level in HBeAg loss/seroconversion group was lower than the patients in the group that not achieved HBeAg loss/seroconversion (1.217 lgS/CO vs 1.884 lgS/CO, t=2.061, P=0.044); the difference was statistically significant in HBsAg, HBeAg decreased at 24 th, 36 th, 48 th week in the course of sequential therapy between the two groups (1.330 vs 0.205, 2.084 vs 0.258, 1.972 vs 0.284, lg IU/ml; 1.168 vs 0.455, 1.363 vs 0.461, 1.177 vs 0.447, lg S/CO) (t=2.238, P=0.049; t=2.619, P=0.025; t=2.278, P=0.048); (t=2.273, P=0.043; t=3.415, P=0.001; t=2.271, P=0.049). Conclusions To HBeAg-positive CHB, lower baseline HBsAg, HBeAg level and HBsAg, HBeAg decreased earlier were could predict easier achievement of HBs(e)Ag loss/seroconversion.

Objective: To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV). Methods: Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed. Results: Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes. Conclusions ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.

Objective: To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B. Methods: Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation. Results: Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response. Conclusions The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.