Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). However, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear. AIM: To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders. METHODS: Liver samples were collected from 16 healthy donors (HDs) and 17 advanced HBV-ACLF patients who were eligible for liver transplantation. The mitochondrial ultrastructure, metabolic characteristics, and immune microenvironment of the liver were assessed. More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF. RESULTS: Compared with HDs, there was extensive hepatocyte necrosis, immune cell infiltration, and ductular reaction in patients with ACLF. In patients, the liver suffered severe hypoxia, as evidenced by increased expression of hypoxia-inducible factor-1α. Swollen mitochondria and cristae were observed in the liver of patients. The number, length, width, and area of mitochondria were adaptively increased in hepatocytes. Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased, while anaerobic glycolysis was enhanced in patients with HBV-ACLF. These findings suggested that, to a greater extent, hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source. Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate, which stimulates peripheral monocyte infiltration into the liver. Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68+ HLA-DR+ macrophages and elevated levels of both interleukin-1ß and transforming growth factor-ß1 in their livers. The abundance of CD206+ CD163+ macrophages and expression of interleukin-10 decreased. The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines. CONCLUSION: The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling, leading to advanced HBV-ACLF. These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.

Treatment of functional dyspepsia in Chinese adult patients with domperidone: A multicenter, randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis.

BACKGROUND: Twist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial. AIM: To investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer. METHODS: Published literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated by I 2 statistics. RESULTS: Eleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69, I 2 = 68.6%), and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84 (95%CI: 1.12-3.02, I 2 = 67.1%), suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients. In addition, overexpression of Twist was correlated with T stage (T3 + T4 vs T1 + T2, RR = 1.38, 95%CI: 1.14-1.67), lymph node metastasis (yes vs no, RR = 1.34, 95%CI: 1.11-1.60), distant metastasis (yes vs no, RR = 1.18, 95%CI: 1.02-1.35), tumor, node and metastasis (TNM) stage (III + IV vs I + II, RR = 1.35, 95%CI: 1.14-1.60), and clinical stage (III + IV vs I + II, RR = 1.58, 95%CI: 1.34-1.87). However, no correlation between Twist expression and age, gender, tumor location, differentiation, or venous invasion was observed. CONCLUSION: High expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.

[Medication regularity of combination of traditional Chinese medicine and Western medicine in treating Helicobacter pylori-related gastropathy based on literatures].

The medication rules of combination of traditional Chinese medicine( TCM) and Western medicine in treating Helicobacter pylori-related gastropathy are analyzed to provide reference for clinical Helicobacter pylori-related gastropathy. Relevant literatures on integrated traditional Chinese and Western medicine in the treatment of Helicobacter pylori-related gastropathy were collected in CNKI,Wan Fang,VIP and CBM. Excel software and traditional Chinese medicine inheritance support system were used to establish a prescription database for data mining and analysis of the medication rules. A total of 178 literatures were selected,77 of them indicated TCM syndromes,and the syndrome of dampness-heat in the spleen and stomach had the highest frequency. A total of 207 prescriptions were used,including 100 classic prescriptions,and Banxia Xiexin Decoction had the highest frequency. Traditional Chinese medicine materials were used for 3 027 times,involving 207 herbs,and the top three mostly frequently used herbs were Glycyrrhiza uralensis,Coptis chinensis,and Pinellia ternata. The herbs mostly featured cold and warm properties in four natures,and bitterness and pungent in five flavors,and enter spleen,stomach and liver meridians. Totally 21 core drug combinations and 12 new prescriptions were obtained. According to data mining,the treatment of Helicobacter pylori-related gastropathy gives priority to " dispelling evil" " tonifying deficiency" and regulating Qi. The medication rules were the combination of cold and warm herbs and the compatibility of acrid opening and bitter down-bearing herbs. This provides a certain reference for optimizing clinical prescriptions,improving efficacy,and developing new drugs.

[Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease].

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×109/L. CD4+T cells in two patients were less than 200×106/L. Four patients had elevated serum cytomegalovirus DNA. The level of ß-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

A novel fully automated system for quantification of Hepatitis B virus DNA using magnetic bead-based method combined with real-time PCR.

BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem and causes liver damage as cirrhosis of the liver or liver cancer. Development of an accurate, sensitive and reproducible detection method for detecting and monitoring HBV DNA is very necessary and urgent. OBJECTIVES: The aims were to evaluate the analytical performances of the fully automated Pre-NAT system comparing to domestic assay, and to explore the role of highly sensitive quantification of HBV DNA in the management of chronic HBV infection. STUDY DESIGN: Pseudo-viral particles at high HBV DNA concentration were serially diluted to assess linear range. Accuracy and lower limit of detection were assessed by determining a panel of HBV standard substance. HBV DNA positive clinical specimen and internal quality control were measured 20 times to evaluate precision and reproducibility. 20 non HBV-infected specimens were used for the specificity assay. 96 chronic hepatitis B samples were quantified for HBV DNA to evaluating the correlation between the new test and Da-an assay. HBV serological markers were detected using ELISA method. RESULTS: Pre-NAT quantitated HBV DNA levels covered a wide dynamic range (10 logs) with a close correlation between expected and observed values (r=0.999, P<0.05), satisfactory precision and higher specificity. The lower detection limit was 20IU/mL. Comparability assay showed Pre-NAT had a good agreement with but more sensitive than Da-an assay (t=0.149, P>0.05). HBV DNA level was partially correlated to but more reliable and sensitive than serological evidence in reflecting the viral level. CONCLUSION: This novel fully-automated real-time PCR assay exhibits good analytical and clinical performances for highly sensitive detection of HBV DNA. It is well suited for monitoring antiviral responses and making treatment strategies according to current clinical practice guidelines for the management of chronic HBV infection.

Differentiation of mass-forming intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma: based on the multivariate analysis of contrast-enhanced computed tomography findings.

PURPOSE: We aim to gain further insight into identifying differential radiological features of mass-forming intrahepatic cholangiocarcinoma (mICC) from poorly differentiated hepatocellular carcinoma (pHCC) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS: 107 patients with pathologically confirmed mICC (n = 48) and pHCC (n = 59) who had undergone preoperative contrast-enhanced CT were enrolled. Qualitative analysis of CT images were evaluated for tumor demarcation, shape, presence of satellite nodules, capsular retraction, biliary involvement, intratumoral arteries, tortuous tumoral vessels, vascular invasion, portal vein tumor thrombus, arterial enhancement pattern, portal venous phase enhancement, and washout pattern. Quantitative analysis was performed for mean attenuation of tumor and tumor-to-liver contrast during each phase. The degree of arterial enhancement was graded based on quantitative measurements. RESULTS: A lobulated shape, indistinct margin, peripheral rim enhancement in the arterial phase, and the presence of bile duct dilatation were CT features favoring mICC, whereas a round shape, partially indistinct margin, heterogeneous enhancement in the arterial phase, washout pattern and the presence of tortuous tumoral vessels were CT features favoring pHCC in the univariate analysis (P < 0.05). Tumor-to-liver contrast of pHCC was greater than that of mICC during the arterial phase (P = 0.015). In the multivariate analysis, bile duct dilatation, tortuous tumoral vessels, and a washout pattern were independent CT features for distinguishing between the two types. (P = 0.003, P = 0.003, P = 0.044, respectively). CONCLUSION: The absence of a washout pattern and tortuous tumoral vessels and presence of bile duct dilatation are more indicative of mICC than of pHCC on contrast-enhanced CT.

Endoscopic ultrasound in restaging and predicting pathological response for advanced gastric cancer patients after neoadjuvant chemotherapy.

AIM: To evaluate the role of endoscopic ultrasound (EUS) in restaging and predicting response after neoadjuvant chemotherapy in patients with advanced gastric cancer. METHODS: In all, 48 advanced gastric cancer patients were recruited from June 2007 to December 2010 after providing their written, informed consent. All patients underwent an EUS before and after three cycles of neoadjuvant chemotherapy (FOLFOX 6), and then a radical resection was performed 3-4 weeks after chemotherapy. The results of EUS were compared to the pathological results of the resected specimens. RESULTS: After chemotherapy, the overall sensitivity of EUS for T classification was 63 percent (T2: 44%, T3: 68%, T4: 90%), and overstaging (31%) was more frequent than understaging (6%). The sensitivity and specificity of EUS for N classification were 56 and 50 percent, respectively (N0: without lymph node metastasis, N1: with lymph node metastasis), with 15 percent overstaged and 32% understaged. EUS revealed that T and/or N downstaging occurred in 46 percent (22/48) of patients after chemotherapy, most of whom had a favorable pathological response to the chemotherapy compared with other patients without T and/or N downstaging. No T or N upstaging was observed after neoadjuvant chemotherapy. CONCLUSIONS: The accuracy of restaging by EUS for T and N classification was not as good as pathological data for locally advanced gastric cancer patients after neoadjuvant chemotherapy. However, T and/or N downstaging confirmed by EUS correlated well with the degree of pathological response to chemotherapy.

Pancreaticobiliary duct changes of periampullary carcinomas: quantitative analysis at MR imaging.

PURPOSE: To quantitatively analyse the pancreaticobiliary duct changes of periampullary carcinomas with volumetric interpolated breath-hold examination (VIBE) and true fast imaging with steady-state precession (true FISP) sequence, and investigate the value of these findings in differentiation and preoperative evaluation. MATERIALS AND METHODS: Magnetic resonance (MR) images of 71 cases of periampullary carcinomas (34 cases of pancreatic head carcinoma, 16 cases of intrapancreatic bile duct carcinoma and 21 cases of ampullary carcinoma) confirmed histopathologically were analysed. The maximum diameter of the common bile duct (CBD) and main pancreatic duct (MPD), dilated pancreaticobiliary duct angle and the distance from the end of the proximal dilated pancreaticobiliary duct to the major papilla were measured. Analysis of variance and the Chi-squared test were performed. RESULTS: These findings showed significant differences among the three subtypes: the distance from the end of proximal dilated pancreaticobiliary duct to the major papilla and pancreaticobiliary duct angle. The distance and the pancreaticobiliary duct angle were least for ampullary carcinoma among the three subtypes. The percentage of dilated CBD was 94.1%, 93.8%, and 100% for pancreatic head carcinoma, intrapancreatic bile duct carcinoma and ampullary carcinoma, respectively. And that for the dilated MPD was 58.8%, 43.8%, and 42.9%, respectively. CONCLUSION: Quantitative analysis of the pancreaticobiliary ductal system can provide accurate and objective assessment of the pancreaticobiliary duct changes. Although benefit in differential diagnosis is limited, these findings are valuable in preoperative evaluation for both radical resection and palliative surgery.

[Whole-liver perfusion scans with 64-slice spiral CT in patients with liver cirrhosis].

OBJECTIVE: To test the value of whole-liver perfusion in demonstrating liver angiography and assessing the degree of liver cirrhosis. METHODS: Forty patients with confirmed liver cirrhosis (patient group) and twenty patients without any liver abnormalities (control group) were prospectively enrolled in this study. All patients underwent whole-liver perfusion CT scans. The time density curve (TDC), hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP) and total liver perfusion (TLP) were measured using a special software for the whole-liver perfusion. The CTA imaging of hepatic vessels was obtained by reconstructing the single scanning images. The peak values and time to reach peak values of abdominal aorta and portal veins and the hepatic perfusion parameters were measured. The collateral vessels were observed. RESULTS: Delay in the time to reach peak values and reduced peak values of the abdominal aorta and portal veins in patients with live cirrhosis were observed compared to the controls (P < 0.05). The HAP value in Child A was higher than those in Child B, C and the controls (P < 0.05). The HPP and TLP values decreased gradually in Child A, B and C, all with significance compared to the controls (P < 0.05). The HPI values in Child C was higher than those in other groups (P < 0.05). Reconstructed CTA images showed that different collateral vessels were developed at the end-stage of chronic liver cirrhosis due to severe portal hypertension. The parameters of HPP and TLP in the group with more collateral vessels development were greater than those in other groups (P < 0.05). CONCLUSION: The whole-liver perfusion is valuable in evaluation the severity of liver cirrhosis. The CT angiography can precisely illustrate the hepatic vascular anatomy of liver and the collateral vessels.

Ectopic pancreaticobiliary drainage accompanied by proximal jejunal adenoma: a case report.

A patient with obstructive jaundice was examined by multidetector row helical computed tomography (MDCT) and magnetic resonance imaging (MRI), and his common bile duct was observed to be leading into the distal portion of the horizontal duodenum with a pancreaticobiliary union outside the duodenal wall. A mass was also found in the proximal jejunum. All the above findings were confirmed by subsequent surgery, thus contrast-enhanced MDCT and MRI with appropriate image post-processing could provide non-invasive and accurate information regarding anatomy and lesions of the pancreaticobiliary duct and duodenal union, which may improve the feasibility of surgery and reduce postoperative complications.

First-principles determinations and investigations of the electronic absorption and third-order polarizability spectra of electron donor-acceptor chromophores tetraalkylammonium halide/carbon tetrabromide.

Calculations on donor-acceptor molecular pairs of tetraalkylammonium halide/carbon tetrabromide complexes are provided to investigate structure/property-related linear and nonlinear optical properties by using the time-dependent density functional theory technique coupled with the sum-over-states method. The calculated energies of the first allowed electronic transition decrease, and the nonresonant third-order polarizabilities at the THG, EFISHG, and DFWM optical processes increase progressively from [DBU-H+Br-.CBr(4) to [NPr(4)Br.CBr(4)] to [NMe(4)Br.CBr(4)]. The obtained electronic absorption spectra show a progressive red shift with increasing donor strength from Cl to I for [NR(4)h.CBr(4)] (h = Cl, Br, and I). The charge transfers from the halogen donor to the carbon tetrabromide acceptor make significant contributions to the electronic absorption spectra in the low-energy zone and the third-order polarizabilities in the nonresonant frequency region. The counterion indirectly affects the electronic absorption and third-order polarizability spectra through the interactions between the donor and acceptor.

From molecule to bulk material: optical properties of hydrogen-bonded dimers [C12H12N4O2AgPF6]2 and [C28H28N6O3AgPF6]2 depend on the arrangement of the oxime moieties.

The dependence of the optical properties of [C(12)H(12)N(4)O(2)AgPF(6)](2) (dimer-1) and [C(28)H(28)N(6)O(3)AgPF(6)](2) (dimer-2) on the arrangement of the oxime moieties in the molecule and in bulk crystals was investigated by means of time-dependent density functional theory. Dimer-1 with simple pyridine oxime ligands and a wavy arrangement has a smaller dipole moment and larger transition energy between the two states, and thus smaller third-order polarizabilities and two-photon absorption cross sections. Dimer-2 with extended pyridine oxime ligands and a ladder arrangement has a larger dipole moment and smaller transition energy between the two states, and thus larger third-order polarizabilities and two-photon absorption cross sections. The lowest energy absorption band is red-shifted for dimer-2 as compared with dimer-1, due to more pronounced pi-pi delocalization interactions and weaker hydrogen bonding in dimer-2. The electronic absorption spectra, frequency-dependent third-order polarizabilities, and two-photon absorption cross sections involve significant contributions from charge transfers from pi/pi* orbitals of the pyridine oxime ligands but no contribution from PF(6) (-) ions or H(2)O molecules in the wavelength range studied for the monomers and dimers of the C(12)H(12)N(4)O(2)AgPF(6) and C(28)H(28)N(6)O(3)AgPF(6) molecules. The third-order susceptibilities and two-photon absorption coefficients of bulk solids were estimated on the basis of the optical properties of the corresponding dimers, and the bulk material constructed from dimer-2 has the larger optical parameters of the two.

Synthesis, crystal structure, and optical properties of LiGd5P2O13, a layered lithium gadolinium phosphate containing one-dimensional Li chains.

A lithium gadolinium phosphate crystal, LiGd5P2O13, has been synthesized by a high temperature solution reaction and solved by single-crystal X-ray diffraction data. The structure is monoclinic, space group C2/m, with unit cell parameters a = 18.645(3), b = 5.6257(5), c = 12.014(2) A, beta = 117.55(6)degrees, V = 1117.3(3) A3, and Z = 4. LiGd5P2O13 presents a new structural type and is built up from [Gd5P2O13]- layers and one-dimensional Li chains with an unusual Li-Li distance. The optical properties were investigated in terms of the absorption and emission spectra. Additionally, the calculations of band structure, density of states, dielectric constants, and refractive indexes were performed with the density functional threory method. The obtained results tend to support the experimental data.

Theoretical study of two-photon absorption in donor-acceptor chromophores tetraalkylammonium halide/carbon tetrabromide.

Two-photon absorption properties of a series of donor-acceptor chromophores of tetraalkylammonium halide/carbon tetrabromide ([NR4h.CBr4], h = Cl, Br, I; R = Me, Et, Pr) complexes are investigated in terms of the calculated results by the time-dependent density functional theory (TDDFT) technique combined with the sum-over-states (SOS) method. The modeling two-photon absorption spectra show that these charge-transfer complexes have large two-photon absorption (TPA) cross sections and the [NEt4I.CBr4] has the largest TPA cross section delta with the value of 5.0 x 10(-45) cm4 s photon(-1). The maximum values of delta increase with increasing separations between the donor/acceptor in the order Cl...Br < Br...Br < I...Br for [NEt4h.CBr4] complexes; however, the TPA cross sections delta vary slightly as the size of the alkyl group increases from methyl to propyl for the bromide as a donor, and the maximum wavelength of the TPA peak lambdamax indicates a bathochromic shift. The charge transfers from the halide anion to the carbon tetrabromide make a significant contribution to the excited states, and the donor-acceptor charge transfer plays an important role in the TPA activity, whereas changes in size of alkyl group do not make a substantial contribution to TPA.