Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

IL-22-producing CD3 + CD8- T cells increase in immune clearance stage of chronic HBV infection and correlate with the response of Peg-interferon treatment.

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in. chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells.

Tea consumption is inversely associated with depressive symptoms in the elderly: A cross-sectional study in eastern China.

BACKGROUND: Epidemiological studies suggest that higher tea consumption was associated with lower risk of depressive symptoms, but this has not been found consistently. Moreover, the effect of different types of tea on depressive symptoms needs to be further explored. This study aimed to examine the association between tea consumption and depressive symptoms in Chinese elderly. METHODS: We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program including 9371 participants. Depressive symptoms was assessed through the application of Patient Health Questionnaire-9 scale (PHQ-9). Logistic regression models, controlled for an extensive range of potential confounders, were generated to evaluate the association between tea consumption and risk of depressive symptoms. RESULTS: The black tea drinkers had a significantly decreased risk of depressive symptoms (p<0.01), whereas no association was found in green tea drinkers. Compared with non-drinkers, the adjusted ORs (95% CIs) were 0.48 (0.23, 0.99) and 0.35 (0.17, 0.72) for participants consuming <3 cups and ≥3 cups of black tea per day, respectively (P for trend: <0.01). A linear association between concentration of black tea and depressive symptoms was also confirmed in our study. LIMITATIONS: Cross-sectional data could not make a causation conclusion, and the observed association in our study could not be ascribed to any specific component in tea. CONCLUSIONS: Our results indicated that higher black tea consumption was associated with a lower prevalence of depressive symptoms in the elderly.

Pharmacokinetic study of four flavones of Glycyrrhiza in rat plasma using HPLC-MS.

AIM OF THE STUDY: This study aimed to develop a specific HPLC-MS method for simultaneous quantification of four flavones of Glycyrrhiza in rat plasma after oral administration and to describe the pharmacokinetics of four flavones in rat plasma. MATERIALS AND METHODS: A simple, sensitive and selective method for simultaneous determination of four flavones of Glycyrrhiza in rat plasma, i.e., liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin, by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) with negative electrospray ionization mode, was developed and validated. The method was applied to investigate the pharmacokinetics of four flavones in rat plasma after oral administration of Glycyrrhiza flavones. Chromatographic separation was accomplished on an Agilent TC-C18 column (4.6mm×250mm, and 5µm), with gradient elution by using a mixture of methanoic acid (A) and acetonitrile (B) as the mobile phase at a flow rate of 0.8mL/min. RESULTS: The calibration curves for four flavones had good linearity higher than 0.997 in the measured range. Relative standard deviations (RSDs) of the intra- and inter-day precision at different levels were all less than 4.8%. The pharmacokinetic profile of four flavones in rat plasma was fitted with a two-compartment model detected by a simple, rapid and accurate HPLC-MS method. Time (h) to reach peak concentration (µg/mL) of liquiritin (2.69±0.04), isoliquiritin (10.16±0.02), liquiritigenin (2.83±0.02), and isoliquiritigenin (0.28±0.01) was 2.02±0.23, 1.97±0.20, 0.48±0.02, and 1.93±0.36, respectively. The distribution and elimination half-life (h) and area under the concentration-time curve (µg/mL-h) from t=0 to last time of liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin were 1.02±0.48/2.27±0.53/16.97±0.43, 2.04±1.01/2.38±0.80/69.20±5.24, 0.35±0.10/4.26±0.16/14.83±0.11, and 1.18±0.32/3.04±0.22/2.10±0.09, respectively. Isoliquiritin presented the phenomenon of double peaks and the others appeared together in a single and plateau absorption phase. Isoliquiritigenin had the lowest oral bioavailability because of Cmax and AUC0-∞. Liquiritigenin had the fastest absorption and distribution rate and the lowest elimination rate according to Tmax, t1/2α, and t1/2ß. CONCLUSIONS: This paper first reported on identification and determination of four flavones of Glycyrrhiza in rat plasma and their respective pharmacokinetic characteristics. The results provided a meaningful basis for better understanding the absorption mechanism of Glycyrrhiza and evaluating the clinical application of this medicine.

Simultaneous quantitative determination of nine active chemical compositions in traditional Chinese medicine Glycyrrhiza by RP-HPLC with full-time five-wavelength fusion method.

A new, simple, accurate and reliable full-time five-wavelength fusion method for the simultaneous separation and determination of nine active chemical compositions (liquiritin apioside, liquiritin, isoliquiritin apioside, ononin, isoliquiritin, liquiritigenin, calycosin, isoliquiritigenin, Glycyrrhizic acid monoammonium salt) in traditional Chinese medicine Glycyrrhiza was developed using reverse phase high-performance liquid chromatography (RP-HPLC) coupled with a diode-array detector (DAD). The chromatographic separation was performed on an Agilent TC-C18 column with gradient elution using 0.04% methanoic acid (A) and acetonitrile (B) at a flow rate of 1.0 mL min(-1) and UV detection at 248 nm, 250 nm, 276 nm, 362 nm, 370 nm. The standard curves were linear over the range of 2.1379-12.8272 µg for liquiritin apioside, 3.9299-23.5794 µg for liquiritin, 1.0432-6.2592 µg for isoliquiritin apioside, 0.8764-5.8584 µg for ononin, 1.0701-6.4205 µg for isoliquiritin, 1.3685-8.2111 µg for liquiritigenin, 0.3927-2.3563 µg for calycosin, 0.2498- 1.4986 µg for isoliquiritigenin, 2.0094-12.0564 µg for Glycyrrhizic acid monoammonium salt, respectively (r(2) > 0.9997). The recoveries and relative standard deviation (RSD) varied from 95.09% to 103.54% and 1.09% to 2.36%, respectively. The precision for all the analytes was less than 2.52%. The method indicated good performance in terms of precision, accuracy and linearity. The method enabled the simultaneous determination of nine active chemical compositions for quality control of Glycyrrhiza.

Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice.

AIM: To investigate the anti-tumor effect of Chinese medicine Gecko on human esophageal carcinoma cell lines and xenografted sarcoma 180 in Kunming mice and its mechanism. METHODS: The serum pharmacological method was used in vitro. The growth rates of the human esophageal carcinoma cells (EC9706 or EC1) were measured by a modified 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transplanted tumor model of the mouse S180 sarcoma was established. Fifty mice were randomly divided into five groups (n=10). Three Gecko groups were treated respectively with oral administration of Gecko powder at a daily dose of 13.5 g/kg, 9 g/kg, and 4.5 g/kg. The negative group (NS group) was treated with oral administration of an equal volume of saline and the positive group (CTX group) was treated with 100 mg/kg Cytoxan by intraperitoneal injection at the first day. After 2 wk of treatment, the anti-tumor activity was evaluated by tumor tissue weighing. The impact on immune organ was detected based on the thymus index, spleen index, phagocytic rate and phagocytic index. The protein expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by immunohistochemistry. The cell apoptotic rate was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The OD value in each group treated with Gecko after 72 h was reduced significantly in EC9706 and in EC1. The tumor weight in each group of Gecko was decreased significantly (1.087+/-0.249 vs 2.167+/-0.592; 1.021+/-0.288 vs 2.167+/-0.592; 1.234+/-0.331 vs 2.167+/-0.592; P<0.01, respectively). However, the thymus index and Spleen index of mice in Gecko groups had no significant difference compared with the NS group. The immunoreactive score of VEGF and bFGF protein expression of each Gecko group by immunohistochemical staining were lowered significantly. The apoptosis index (AI) of each group was increased progressively with increase of dose of Gecko by TUNEL. CONCLUSION: Gecko has anti-tumor effects in vitro and in vivo; induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF may be contributed to anti-tumor effects of Gecko.

[Comparison of the anti-fertility effects of four extracts from the roots of Rhynchosia volubilis Lour].

OBJECTIVE: To compare the anti-fertility effects of the four extracts from the roots of Rhynchosia volubilis Lour on male mice, that is, ethanolic extract, ethyl acetate extract, n-butanol extract and aqueous extract. METHODS: Four extracts from the roots of Rhynchosia volubilis Lour (1%, 0.1 ml/10 g), were administered orally for 11 weeks to adult male mice. The fertility and testicular function of the mice were assessed by mating tests and analyses of sperm motility in cauda epididymides and biochemical and histological indexes in the blood samples and reproductive organs. RESULTS: The four extracts, especially aqueous extract, gradually decreased the pregnancy rate of the experimental mice from the 77th day of the treatment, with an obvious reduction in the number of spermatozoa. Morphological observation of the reproductive organs by light microscopy showed that the numbers of the secondary spermatocytes and spermatids were decreased in varied degrees, and the seminiferous tubules were disarranged, while the numbers and shapes of and spermatids were decreased in varied degrees, and the seminiferous tubules were disarranged, while the numbers and shapes of spermatogonia, Sertoli cells and Leydig cells remained unchanged. CONCLUSION: The four extracts from the roots of Rhynchosia volubilis Lour all have anti-fertility effects on male mice, and that of the aqueous extract is more obvious.

[Inhibitory effect on male mouse procreation and chemical composition analysis of Rhynchosia volubilis ethyl acetate extract].

OBJECTIVE: To study the effect of Rhynchosia volubilis Lour ethyl acetate extract (RVLEAE) on male mouse procreation and analyse their chemical composition. METHOD: With the method of solvent extraction, RVLEAE was extracted and concentrated. In the experiment of mice, 80 male mice were randomly and equally divided into four groups: Normal Saline control, positive control with 0.1% triperygium wilfordii glycoside, 100 mg x kg(-1) x d(-1) RVLEAE and 400 mg x kg(-1) x d(-1) RVLEAE. Every mouse was fed with drug 0.01 mL x g(-1), once a day, ig, for eleven consecutive weeks. After two and 10 weeks, male and female mouse naturally mated for one week. The pregnancy rate, number of fetus and nonviable fetus, the viability of spermatozoon in the epididymis cauda, pathological change of testis and epididymis were observed in this experiment. In the analysis of chemical composition, RVLEAE were separated with column chromatography, and chemical compositions were identified with thinlayer chromatography, infrared chromatography and nuclear magnetic resonance. RESULT: The pregnancy rate of mice was markedly decreased. The number and viability of spermatozoon were slightly reduced in I and II after two and 10 weeks, but the pathological changes of testis and epididymis were markedly occurred. Main chemical compositions were identified as saccharide, glycosides especially analog of fucose, alcohols, and phenols. CONCLUSION: RVLEAE can inhibit the procreation of male mice, and inhibitory target tissue may be the epididymis. Active mechanism of RVLEAE may be that glycosides interfere the maturation of spermatozoon in the epididymis cauda.