Metabolomic Profiling Reveals the Quality Variations in Citri Reticulatae Pericarpium (Citrus reticulata Blanco cv. Chachiensis) with Different Storage Ages in Response to "Candidatus Liberibacter Asiaticus" Infection.

Citri Reticulatae Pericarpium, especially the pericarp of Citrus reticulata Blanco cv. Chachiensis (PCRC), is an important edible and medicinal ingredient for health and pharmacological properties. Citrus Huanglongbing, a devastating disease that currently threatens the citrus industry worldwide, is caused by a phloem-limited alpha-proteobacterium, "Candidatus Liberibacter asiaticus" (CLas). The industry of cultivar Chachiensis has been suffering from HLB. Although HLB affected the quality of citrus fruit, whether the quality of PCRC was affected by HLB remains unclear. In this study, we compared the metabolite profiles between HLB-affected and healthy PCRC from three sources: fresh, 6-month-old, and 9-year-old PCRC, through the untargeted LC-MS method. Compared to healthy controls, various types of bioactive compounds, mainly flavonoids, terpenoids, alkaloids, coumarins, polysaccharides, and phenolic acids, accumulated in HLB-affected PCRC, especially in the HLB-affected 9-year PCRC. In particular, isorhamnetin, isoliquiritigenin, luteolin 7-O-beta-D-glucoside, limonin, geniposide, pyrimidodiazepine, scoparone, chitobiose, m-coumaric acid, malonate, and pantothenic acid, which contributed to the pharmacological activity and health care effects of PCRC, were highly accumulated in HLB-affected 9-year-old PCRC compared to the healthy control. Multibioassay analyses revealed that HLB-affected 9-year-old PCRC had a higher content of total flavonoids and total polyphenols and exhibited similar antioxidant capacity as compared to healthy controls. The results of this study provided detailed information on the quality of HLB-affected PCRC.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

Response of nitrite accumulation, sludge characteristic and microbial transition to carbon source during the partial denitrification (PD) process.

Partial denitrification (PD, nitrate (NO3--N) â†’ nitrite (NO2--N)) as a novel pathway for NO2--N production has been widely concerned, but the specific conditions for highly efficient and stable nitrite maintenance are not yet fully understood. In this study, the effects of carbon sources (acetate, R1; propionate, R2; glucose, R3) on NO2--N accumulation was discussed without seeding PD sludge and the mechanism analysis related to sludge characteristic and microbial evolution were elucidated. The optimal NO2--N, nitrate-to-nitrite transformation ratio (NTR) and nitrite removal efficiency (NRE) reached up to 32.10 mg/L, 98.01 %, and 86.95 % in R1. However, due to the complex metabolic pathway of glucose, the peak time of NO2--N production delayed from 30 min to 60 min. The sludge particle size decreased from 154.2 µm (R1), 130.8 µm (R2) to 112.6 µm (R3) with the increasing extracellular polymeric substances (EPS) from 80.75-85.44 mg/gVSS, 82.68-92.75 mg/gVSS to 106.31-110.25 mg/gVSS, where the ratio of proteins/polysaccharides (PN/PS) was proved to be closely associated with NO2--N generation. For the microbial evolution, Saccharimonadales (70.42 %) dominated the glucose system, while Bacillus (7.42-21.63 %) and Terrimonas (4.24-5.71 %) were the main contributors for NO2--N accumulation in the acetate and propionate systems. The achievement of PD showed many advantages of lower carbon demand, minimal sludge production, lesser greenhouse gas emission and prominent nutrient removal, offering an economically and technically attractive alternative for NO3--N containing wastewater treatment.

Pathogenicity and Transcriptomic Analyses of Two "Candidatus Liberibacter asiaticus" Strains Harboring Different Types of Phages.

"Candidatus Liberibacter asiaticus" is one of the putative causal agents of citrus Huanglongbing (HLB), a highly destructive disease threatening the global citrus industry. Several types of phages had been identified in "Ca. Liberibacter asiaticus" strains and found to affect the biology of "Ca. Liberibacter asiaticus." However, little is known about the influence of phages in "Ca. Liberibacter asiaticus" pathogenicity. In this study, two "Ca. Liberibacter asiaticus" strains, PYN and PGD, harboring different types of phages were collected and used for pathogenicity analysis in periwinkle (Catharanthus roseus). Strain PYN carries a type 1 phage (P-YN-1), and PGD harbors a type 2 phage (P-GD-2). Compared to strain PYN, strain PGD exhibited a faster reproduction rate and higher virulence in periwinkle: leaf symptoms appeared earlier, and there was a stronger inhibition in the growth of new flush. Estimation of phage copy numbers by type-specific PCR indicated that there are multiple copies of phage P-YN-1 in strain PYN, while strain PGD carries only a single copy of phage P-GD-2. Genome-wide gene expression profiling revealed the lytic activity of P-YN-1 phage, as evidenced by the unique expression of genes involved in lytic cycle, which may limit the propagation of strain PYN and lead to a delayed infection in periwinkle. However, the activation of genes involved in lysogenic conversion of phage P-GD-1 indicated it could reside within the "Ca. Liberibacter asiaticus" genome as a prophage form in strain PGD. Comparative transcriptome analysis showed that the significant differences in expression of virulence factor genes, including genes associated with pathogenic effectors, transcriptional factors, the Znu transport system, and the heme biosynthesis pathway, could be another major determinant of virulence variation between two "Ca. Liberibacter asiaticus" strains. This study expanded our knowledge of "Ca. Liberibacter asiaticus" pathogenicity and provided new insights into the differences in pathogenicity between "Ca. Liberibacter asiaticus" strains. IMPORTANCE Citrus Huanglongbing (HLB), also called citrus greening disease, is a highly destructive disease threatening citrus production worldwide. "Candidatus Liberibacter asiaticus" is one of the most common putative causal agents of HLB. Phages of "Ca. Liberibacter asiaticus" have recently been identified and found to affect "Ca. Liberibacter asiaticus" biology. Here, we found that "Ca. Liberibacter asiaticus" strains harboring different types of phages (type 1 or type 2) showed different levels of pathogenicity and multiplication patterns in the periwinkle plant (Catharanthus roseus). Transcriptome analysis revealed the possible lytic activity of type 1 phage in a "Ca. Liberibacter asiaticus" strain, which could limit the propagation of "Ca. Liberibacter asiaticus" and lead to the delayed infection in periwinkle. The heterogeneity in the transcriptome profiles, particularly the significant differences in expression of virulence factors genes, could be another major determinant of difference in virulence observed between the two "Ca. Liberibacter asiaticus" strains. These findings improved our understanding of "Ca. Liberibacter asiaticus"-phage interaction and provided insight into "Ca. Liberibacter asiaticus" pathogenicity.

SATB1/SLC7A11/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection.

Neuronal damage after ischemic stroke (IS) is frequently due to ferroptosis, contributing significantly to ischemic injury. However, the mechanism against ferroptosis in IS remained unclear. The aim of this study was to investigate the potential mechanism of Danhong injection (DHI) and the critical transcription factor SATB1 in preventing neuronal ferroptosis after ischemic stroke in vivo and in vitro. The results showed that DHI treatment significantly reduced the infarct area and associated damage in the brains of the pMCAO mice, and enhanced the viability of OGD-injured neurons. And several characteristic indicators of ferroptosis, such as mitochondrial necrosis and iron accumulation, were regulated by DHI after IS. Importantly, we found that the expression and activity of SATB1 were decreased in the pMCAO mice, especially in neuron cells. Meanwhile, the SATB1/SLC7A11/HO-1 signaling pathway was activated after DHI treatment in ischemic stroke and was found to improve neuronal ferroptosis. Inhibition of SATB1 significantly reduced SLC7A11-HO-1 and significantly attenuated the anti-ferroptosis effects of DHI in the OGD model. These findings indicate that neuronal ferroptosis after IS can be alleviated by DHI through SATB1/SLC7A11/HO-1 pathway, and SATB1 may be an attractive therapeutic target for treating ischemic stroke.

Colonization with Carbapenem-Resistant Enterobacteriaceae Contributes to Unfavorable Outcomes in End-Stage Liver Disease Patients.

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the relationship between CRE colonization, infection, and prognosis in patients with ESLD. A total of 311 patients with ESLD were screened for CRE colonization by fecal swabs from October 2020 to January 2022. Antimicrobial susceptibility was tested using the broth microdilution method. Carbapenem resistance genes, multilocus sequence type, and capsular serotype were analyzed by polymerase chain reaction (PCR). Seventeen CRE strains were detected, among which the most common was Klebsiella pneumoniae. The CRE colonization rate was 5.5%. Artificial liver support was an independent risk factor for CRE colonization. Compared to the non-CRE colonization group, the colonization group had a higher incidence of CRE infection and a worse prognosis. Furthermore, these strains were not closely related, and all were sensitive to polymyxin and tigecycline. There was a high colonization rate in ESLD patients, and colonization strains were highly diverse. CRE colonization deserves attention in these patients, especially when treated with artificial liver support.

Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy.

Cerebral ischemia/reperfusion (I/R) injury is the result of ischemic stroke, a serious threat to public health. I/R injury can damage the blood-brain barrier (BBB), adversely affecting the brain environment and aggravating the injury. Cyclo-(Phe-Tyr) (sparganin C, SC) is a small molecule derived from the Chinese yam Dioscorea opposita Thunb. or Sparganii rhizoma. In our previous study, SC mitigates I/R injury both in vivo and in vitro through the action of JUNB and SOX5. However, the exact pharmacological effects of SC on BBB protection after an I/R injury remain unclear. We constructed a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) injury to evaluate the therapeutic actions of SC, and the integrity of the BBB was evaluated by ELISA, western blotting, and Evans blue staining. It was found that SC significantly reduced the amount of Evans blue staining in the brain, inhibited the expression of inflammatory factors IL-6, IL-1ß, IL-17, IL-23, and TNF-α as well as TIPM1/MMP proteins, and promoted the expression of the tight junction proteins occludin, ZO-1, and claudin-5. SC was found to inhibit the excess autophagy induced by I/R injury to protect BBB integrity through the PI3K/AKT/mTOR pathway, and the PI3K inhibitor LY294002 significantly reduced the SC-mediated protection. Overall, this is the first demonstration of the alleviation of BBB damage caused by I/R injury by SC and suggests a potential treatment for the effects of an ischemic stroke.

Severe skin and subcutaneous pythiosis in China: Metagenomic identification and characterization of Pythium insidiosum.

Pythium insidiosum is a rare fungus-like pathogen that is known to cause pythiosis in mammals with high morbidity and mortality. Identification of the pathogen is essential for timely treatment and rational use of antibiotics. However, Pythium insidiosum is difficult to detect via conventional microbiological tests. The current gold standard is polymerase chain reaction, which is lacking in most hospitals since human pythiosis is rare in China. In this study, we used metagenomic Next-Generation Sequencing and identified Pythium insidiosum in a 56-year-old Chinese male who was hospitalized due to severe edema in the right lower limb with scattered darkening indurations. The patient had a history of cirrhosis and occupational exposure to swamp water. Serological level of immune biomarkers indicated immunodeficiency, and Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody was positive. Surgical incision of the lesions revealed radiating and reticular cutaneous ulcers. Microbial infections were suspected but conventional tests failed to discover the etiology. Empirical use of penicillin, vancomycin, and ceftriaxone had no effect. As a result, the peripheral blood and tissue biopsies were sent for metagenomic Next-Generation Sequencing, which reported Pythium insidiosum. This finding was corroborated by pathological staining, whole-genome sequencing, and internal transcribed spacer sequencing. Notably, antifungal treatment was ineffective, but the patient responded well to oral trimethoprim-sulfamethoxazole, which may be due to the folp gene found in Pythium insidiosum genome. Our study prompts future studies to determine the optimal treatment of skin pythiosis.

Bidirectional mRNA transfer between Cuscuta australis and its hosts.

The holoparasitic dodder (Cuscuta spp.) is able to transfer mRNA and certain plant pathogens (e.g., viruses and bacteria) from the host plant. "Candidatus Liberibacter asiaticus," the phloem-limited causative agent of citrus Huanglongbing, can be transferred from citrus to periwinkle (Catharanthus roseus) mediated by dodder. However, characterization of mRNA transport between dodder and citrus/periwinkle remains unclear. In this study, we sequenced transcriptomes of dodder and its parasitizing host, sweet orange (Citrus sinensis "Newhall") and periwinkle (Catharanthus roseus), to identify and characterize mRNA transfer between dodder and the host plant during parasitism. The mRNA transfer between dodder and citrus/periwinkle was bidirectional and most of the transfer events occurred in the interface tissue. Compared with the citrus-dodder system, mRNA transfer in the periwinkle-dodder system was more frequent. Function classification revealed that a large number of mRNAs transferred between dodder and citrus/periwinkle were involved in secondary metabolism and stress response. Dodder transcripts encoding proteins associated with microtubule-based processes and cell wall biogenesis were transferred to host tissues. In addition, transcripts involved in translational elongation, plasmodesmata, and the auxin-activated signaling pathway were transmitted between dodder and citrus/periwinkle. In particular, transcripts involved in shoot system development and flower development were transferred between the host and dodder in both directions. The high abundance of dodder-origin transcripts, encoding MIP aquaporin protein, and S-adenosylmethionine synthetase 1 protein, in citrus and periwinkle tissues indicated they could play an important biological role in dodder-host interaction. In addition, the uptake of host mRNAs by dodder, especially those involved in seed germination and flower development, could be beneficial for the reproduction of dodder. The results of this study provide new insights into the RNA-based interaction between dodder and host plants.

Cyclo-(Phe-Tyr) as a novel cyclic dipeptide compound alleviates ischemic/reperfusion brain injury via JUNB/JNK/NF-κB and SOX5/PI3K/AKT pathways.

Ischemic/reperfusion (IR) can cause adverse reactions including apoptosis, oxidative stress, and inflammation, but the existing therapeutic strategies have been limited. Moreover, the regulation of microglia plays an important role in brain injury after reperfusion. Hence, it is imperative to find new and effective drugs for modulating microglia to treat IR brain injury. Cyclic peptide compound cyclo-(Phe-Tyr) (Sparganin C, SC) is a compound isolated from Sparganii Rhizoma. However, the protective effects of SC on the central nervous system are rather unclear. In an attempt to elucidate the protective effects and mechanism of SC on cerebral damage induced by the IR, we used a middle cerebral artery occlusion reperfusion (MCAO/R) model in rats and discovered that SC significantly decreased the size of cerebral infarcts, improved neurological scores, and blocked inflammatory and oxidative factor release. Using RNA-Seq and metabolomics association analyses, SC was shown to have a protective impact through the JUNB and SOX5-related pathways. Metabolomic analysis revealed twenty-eight differentially expressed biomarkers. In addition, the detection of SC content in brain tissue using LC/MS revealed that SC had blood-brain barrier penetration. To investigate the mechanism, we established an in vitro BV2 cell oxygen-glucose deprivation/reperfusion (OGD/R) model and used siRNA as well as an inhibitor. The protective effects of SC were dependent on the JUNB and SOX5 to inhibit inflammation and apoptosis in microglia. Our findings revealed for the first that SC against IR injury by reducing inflammation and apoptosis while simultaneously acting as potential therapeutic lead compound for ischemic stroke.

Autoimmune diseases in HIV-negative cryptococcal meningitis.

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

Integrated Analysis of the Cecal Microbiome and Plasma Metabolomics to Explore NaoMaiTong and Its Potential Role in Changing the Intestinal Flora and Their Metabolites in Ischemic Stroke.

Ischemic stroke (IS), as a leading cause of disability worldwide, affects intestinal bacterial communities and their metabolites, while recent discoveries have highlighted the importance of the intestinal microflora in the development of IS. Systematic investigations of complex intestinal bacterial communities and their metabolites during ischemic brain injury contribute to elucidate the promising therapeutic targets for IS. However, the associations between intestinal microbiota and related circulating metabolic processes in IS remained unclear. Hence, to identify the changed microflora and their metabolites in IS of NaoMaiTong (NMT), an effective clinical medication, we established the middle cerebral artery occlusion/reperfusion (MCAO/R) model using conventionalized and pseudo-germ-free (PGF) rats. Subsequently, we systematically screen the microflora and related metabolites changing in IS via an integrated approach of cecal 16S rRNA sequencing combined with plasma metabolomics. We found that NMT relied on intestinal flora to improve stroke outcome in conventionalized rats while the protection of NMT was reduced in PGF rats. Total 35 differential bacterial genera and 26 differential microbial metabolites were regulated by NMT. Furthermore, L-asparagine and indoleacetaldehyde were significantly negatively correlated with Lachnospiraceae_UCG.001 and significantly positively correlated with Lachnoclostridium. Indoleacetaldehyde also presented a negative correlation with Lactobacillus and Bifidobacterium. 2-Hydroxybutyric acid was strongly negatively correlated with Ruminococcus, Lachnospiraceae_UCG.001 and Lachnospiraceae_UCG.006. Creatinine was strongly negatively correlated with Akkermansia. In summary, the research provided insights into the intricate interaction between intestinal microbiota and metabolism of NMT in IS. We identified above differential bacteria and differential endogenous metabolites which could be as prebiotic and probiotic substances that can influence prognosis in stroke and have potential to be used as novel therapeutic targets or exogenous drug supplements.

Structural characterization, anti-inflammatory and glycosidase inhibitory activities of two new polysaccharides from the root of Pueraria lobata.

Diabetes seriously endangers public health and brings a heavy economic burden to the country. Inflammation is one of the main inducing factors of type-2 diabetes (T2D) and may cause some complications of diabetes, such as diabetic encephalopathy and peripheral neuropathy. In-depth research and development of drugs to cure diabetes and complications are of great significance. Pueraria lobate is a medicinal herb used in several countries to treat many diseases. Here, two new polysaccharides (PLB-1-1 and PLB-1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9.1 × 103 Da and 3.8 × 103 Da, respectively. The structure was evaluated by monosaccharide composition, GC-MS and NMR spectroscopy. It was determined that PLB-1-1 comprised →4)-α-d-Glcp-(1→, α-d-Glcp-(1→, →6)-ß-d-Galp-(1→, →3)-α-l-Araf-(1→, →3,6)-ß-d-Manp-(1→ and →4,6)-ß-d-Manp-(1→, and PLB-1-2 consisted of →4)-α-d-Glcp-(1→, ß-d-Glcp-(1→, →4,6)-ß-d-Glcp-(1→, →3,6)-ß-d-Manp-(1→ and α-l-Fucp-(1→. Furthermore, both PLB-1-1 and PLB-1-2 showed anti-inflammatory and inhibitory activities of α-glucosidase and α-amylase in vitro. Therefore, the new polysaccharides, i.e., PLB-1-1 and PLB-1-2, may be considered candidates for the treatment of diabetes and its related complications.

The Immunotherapeutic Effect of SIRPα-Silenced DCs against Cervical Cancer.

Signal regulatory protein α (SIRPα), a transmembrane protein that is predominantly expressed in dendritic cells (DCs) or macrophages, interacts with CD47 that is overexpressed in almost all types of tumor cells. The interaction between SIRPα and CD47 leads to a negative signal that prevents the phenotypic and functional maturation of DC and inhibits phagocytosis. The SIRPα knockdown in DCs that were pulsed with a modified HPV16E7 (HPV16mE7) protein with enhanced antigenicity and reduced transformation activity results in increased cytokine (TNF-α/IL-12/IL-6) secretion, IFN-γ secretion by T lymphocytes, and in vitro/in vivo tumoricidal activity against cervical cancer cells. Taken together, these results suggest that SIRPα-silenced DC vaccination presented potential therapeutic implications against cervical cancer.

Rare Meningitis and Epileptic Seizure Infected with Brucella melitensis: a Case Report.

BACKGROUND: Although brucellosis is the most common zoonotic disease worldwide, human meningitis infected with Brucella melitensis is rare and difficult to diagnosis. Herein we describe the clinical aspects of a rare case of Brucella melitensis meningitis accompanied by epileptic seizure. METHODS: Bacterial culture of CSF was utilized to find the pathogen. Serum and CSF agglutination tests were used to detect the capacity of Brucella antigen. Bacterial clone was identified by the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Magnetic resonance imaging (MRI) was used to monitor the recovery changes for meningitis. RESULTS: The bacterial culture was positive for Brucella app. Antigen-antibody agglutination test was also positive with a titer more than 1/200. A reliable identification score of 2.8 for Brucella melitensis was obtained by MALDI-TOF. MRI showed obviously improved meningitis after therapy. CONCLUSIONS: The results of this study suggest the treatments for Brucella meningitis must be planned depending on the patient's clinical conditions and the laboratory identification of pathogen infection as early as possible.

Fasting Serum Low-Density Lipoprotein (LDL) Before Liver Transplantation Predicts Post-Transplant Survival.

BACKGROUND The disordered metabolism of liver function in liver cancer patients can affect postoperative survival after liver transplantation. We assessed whether the levels of various chemicals in liver metabolism prior to receiving a liver transplant were prognostic factors and metabolism markers in predicting survival rate. MATERIAL AND METHODS Seventy-seven patients received a donor liver transplant between June 2012 and April 2016. The basic level of fasting serum GLU, Crea, TBil, TC, TG, HDL, LDL, ApoA1, ApoB100, INR, and MELD scores of 77 patients were retrospectively analyzed. Each patient's survival was monitored to evaluate prognosis and long-term survival. RESULTS The overall survival rates of all patients post-transplant at 6-, 12-, 24-, and 36-month follow-up were 90.9%, 79.2%, 68.8%, and 64.9% respectively. Fasting serum levels of GLU (P=0.004), HDL (P=0.010), LDL (P=0.008), ApoA1 (P=0.028), and MELD scores (P=0.013) prior to liver transplantation were closely associated with the cumulative survival post-transplant in univariate analyses. Controlled fasting GLU of ≤5.12 mmol/L (P=0.019), LDL of ≤2.62 mmol/L (P=0.031), and MELD scores of ≤9 (P=0.013) before LT were significantly and independently associated with increased cumulative survival in the multivariate analyses. CONCLUSIONS Decreased fasting serum GLU, LDL, and MELD scores as independent risk factors prior to liver transplantation markedly increase cumulative survival.

Serum liver fibrosis markers discriminate significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase.

Chronic liver inflammation caused by chronic hepatitis B virus (CHB) infection leads to liver cirrhosis and hepatocellular carcinoma. Recently, the role of alanine aminotransferase (ALT) as a predictor of liver inflammation has been questioned. The aim of this study was to investigate the utility of noninvasive fibrosis markers including hyaluronic acid (HA), collagen type IV (CIV), N-terminal propeptide of type III procollagen (PIIINP), and laminin (LN) in identifying significant liver inflammation in patients with CHB, especially in patients with normal or near-normal ALT. A total of 242 CHB patients who underwent liver biopsy were enrolled. The serum levels of ALT, aspartate aminotransferase, HA, CIV, PIIINP, and LN were quantified and the relationship between histological staging and serum markers was systematically analyzed. Serum CIV, PIIINP, HA, and LN levels increased significantly along with the increasing severity of liver inflammation. Multivariate analysis showed that CIV and LN were independently associated with significant inflammation. CIV, PIIINP, HA, and LN levels were found to have high diagnostic values for predicting significant inflammation in patients with CHB (area under the curve, AUC = 0.807, 0.795, 0.767, and 0.703, respectively). The combined index for the identification of significant inflammation, including CIV, PIIINP, HA, and LN levels, significantly improved diagnostic performance (AUC = 0.851). Moreover, the combined index also achieved excellent diagnostic accuracy (AUC = 0.861) in patients with CHB with normal or near-normal ALT. In conclusion, the combined index may be a strong indicator for discriminating significant liver inflammation, especially in patients with CHB with normal or near-normal ALT.

Rapidly Progressive, Fata Infection Caused by Bacillus Cereus in a Patient with Acute Lymphoblastic Leukemia.

BACKGROUND: We herein report a fatal case of fulminant septicemia caused by Bacillus cereus in a 49-year-old female with T-cell acute lymphoblastic leukemia receiving chemotherapy. METHODS: Her two blood culture sets were positive for Gram-positive, rod-shaped bacterium. Bacillus cereus was identified by high-throughput MALDI-TOF mass spectrometry and 16S ribosomal RNA gene sequencing. RESULTS: The patient died within 12 hours from the onset of B cereus infection. CONCLUSIONS: Patients with acute leukemia presented with fever and unexplained multiple organ lesions, especially accompanied by CNS symptoms, should alert to the possibility of Bacillus cereus infection.

IL-32γ promotes integrin αvß6 expression through the activation of NF-κB in HSCs.

Hepatic stellate cell (HSC) activation is important in the pathogenesis of liver fibrosis. However, the molecular mechanism of HSC activation is not completely understood. In the present study, it was demonstrated that interleukin-32γ (IL-32γ) is capable of enhancing intefgrin αvß6 expression by inducing integrin αvß6 promoter activity in a dose-dependent manner in HSCs. Furthermore, it was determined that nuclear factor κB (NF-κB) activation is required for IL-32γ-induced integrin αvß6 expression. Increased integrin αvß6 expression is then able to activate HSCs. These results indicate that NF-κB activation is required for IL-32γ to induce integrin αvß6 expression and consequently promote HSC activation. Therefore, IL-32γ activates HSCs and therefore may be associated with hepatic fibrogenesis. These results may enable the development of novel effective strategies to treat hepatic fibrosis.

It was all planned now what? Claiming agency in later life in reforming China.

This study explores the social construction of agency and wellbeing among 20 Chinese urban retirees aged between 50 and 82 years old (averaging 67), with a special focus on the impact of earlier life experiences in shaping later-life pathways. Today's retirees in urban China have experienced the communist collectivist ideology during the Mao era as well as the changes to everyday life brought about by the economic transformation from centrally planned socialism to a market-orientated economy. Thereby, life in retirement for Chinese elders becomes more than just an issue of dealing with increases in discretionary time after exit from full-time work, but also one of making sense of their earlier life experiences in the midst of dramatic social changes. A grounded theory approach with semi-structured, in-depth, face-to-face interviews was used for data collection and analysis. Three interrelated themes emerged: (a) reminiscence as a mechanism of meaning-making, (b) discovery and exercise of agency in later life in contrast to a rigidly structured earlier life, and (c) varying pathways to constructing the life-stage of retirement. The findings have refuted gerontological literature and public discourse that often portray Chinese elders as passive care recipients or helpless dependants. Further, the present study has practical implications for developing policies, designing programmes and providing services to improve the quality of life for today's older Chinese people.