Xia-Yu-Xue Decoction Inhibits Intestinal Epithelial Cell Apoptosis in CCl4-Induced Liver Fibrosis

Background/Aims: Intestine-derived endotoxin is thought to play a role in the development of liver fibrosis. However, the pathological change in the intestine during liver fibrosis is still poorly understood. Here, we investigated the effects of Xia-yu-xue decoction (XYXD) on intestinal inflammation, apoptosis, and tight junction integrity in the carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Murine liver fibrosis was developed by CCI4 treatment three times per week over a 6-week period. The CCl4-treated mice were divided into two groups: the CCl4-water group (n=8, CCl4) and the CCl4-XYXD group (n=8, CCl4+XYXD). The CCl4+XYXD mice were treated with XYXD from the beginning of the first week. The expression of inflammatory cytokines and apoptotic molecules were examined using immunohistochemistry, real-time PCR, and western blot. The intestinal epithelial cell apoptosis was examined by TUNEL staining. The tight junction-related molecules, such as ZO-1, claudin, and occludin in the gut were measured by real-time PCR. Results: In CCl4-treated mice damage of the intestinal epithelia and infiltration of inflammatory cells into the lamina propria and muscular layer were observed. Proinflammatory markers MCP-1, TNF-α, CXCL11, IL-6, and CD68 were significantly increased in the intestinal epithelia in CCI4-treated mice. The expression of pro-apoptotic molecules including Fas and Bax was increased in the intestinal epithelia in CCI4-treated mice compared with that in control. The number of TUNEL-positive intestinal epithelial cells was also markedly increased in CCl4-treated mice. The expression of the tight junction proteins including ZO-1, claudin, and occludin was significantly decreased in CCI4-treated mice compared with that in control mice. Notably, XYXD treatment ameliorated increased inflammatory markers and apoptosis-related molecules and decreased tight-junction proteins in CCl4-treated mice. Conclusion: CCl4-treatment increased expression of proinflammatory cytokines and pro-apoptotic molecules and disrupted tight junction integrity in the intestine. XYXD treatment ameliorated intestinal inflammation, cell death, and tight junction disintegrity induced by CCl4 treatment, suggesting that XYXD inhibits CCl4-mediated liver fibrosis at least in part by ameliorating the intestinal epithelial damage

Nomogram for Individualized Prediction of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis on Conservative Treatment

Background. Portal vein tumor thrombosis (PVTT) is one of the major predictive factors for patients with hepatocellular carcinoma (HCC). The objective of this study was to establish a prognostic nomogram for identifying individual survival outcomes in patients with HCC and PVTT on conservative treatment based on specific factors. Methods. Two hundred and ten patients with HCC and PVTT on conservative treatment in Beijing Ditan Hospital between June 2008 and May 2017 were studied retrospectively as a derivation cohort. We built a nomogram based on independent risk factors for survival prediction. The concordance index (c-index) and a calibration curve were used to evaluate the predictive accuracy. During the study, 102 patients were included at the Putuo Hospital and Third People’s Hospital of Changzhou as a validation cohort. Results. In the derivation cohort, the independent factors for overall survival were identified by multivariate analysis, namely, aspartate aminotransferase ≥119 IU/L, gamma-glutamyl transferase ≥115 IU/L, Child–Pugh class C liver function, creatinine ≥91 μmoI/L, α-fetoprotein ≥400 ng/ml, and largest tumor diameter ≥5 cm. The nomogram had a c-index of 0.737 (95% confidence interval, 0.692–0.782) and the calibration curves fitted well. The median survival time was 4.2 months in the derivation cohort, with an MST of 5 months for BCLC C stage and 1.8 months for BCLC D stage patients. Kaplan–Meier analysis showed significant statistical differences in the 6-month overall survival rates of the primary and validation cohorts after the total scores were divided into three quartiles (low risk: 0–85; intermediate risk: 86–210; high risk: ≥211; p<0.0001 in both cohorts). Conclusions. The nomogram can be a more accurate and individualized prediction for 6-month overall survival of patients with HCC and PVTT on conservative treatment, and it is possible to consider further active interventions for patients in the low-risk group (0–85 scores) to achieve the aim of prolonging survival

Application of fine nursing management for patients undergoing simultaneous bilateral lobectomy (精细化护理干预在同期双侧肺叶切除术患者中的应用)

Objective To investigate the effect of f fine nursing management for patients undergoing simultaneous bilateral lobectomy. Methods Totally 52 patients under simultaneous bilateral lobectomy were randomly divided into the control group and observation group, with 26 cases in each group. The control group received routine nursing interventions during perioperative period. The observation group was given fine nursing management. The indwelling time of catheter, length of postoperative hospital stay, hospitalization costs and postoperative complications were recorded. Results The indwelling time of drainage tube and length of postoperative hospital stay in the observation group were shorter than those in the control group(P＜0. 05). There was a case of pneumothorax, 1 case of stage I pressure injury, 5 cases of arrhythmia, 2 cases of breathing difficulties and 2 cases of incision infection in the observation group. There was a case of pneumothorax, 3 cases of stage I pressure injury, 5 cases of arrhythmia, 1 case of breathing difficulties, 5 cases of incision infection and 1 case of death in the control group. Conclusion Implementation of fine nursing management is effective to shorten indwelling time of drainage tube and length of postoperative hospital stay of patients undergoing simultaneous bilateral lobectomy. (目的 探讨同期双侧肺叶切除围手术期实施精细化护理干预的效果。方法 选取2015年1月—2021年12月医院收治的行同期双侧肺叶切除患者52例, 随机分为对照组和观察组, 各26例。对照组围手术期采取常规护理, 观察组围术期采取精细化护理干预。记录和分析两组患者引流管留置时间、术后平均住院日、住院费用和术后并发症。结果 观察组患者引流管留置时间、术后平均住院日较对照组缩短, 差异有统计学意义(P＜0. 05)。观察组术后发生气胸1例, I期压疮1例, 心律失常5例, 呼吸困难2例, 切口感染2例; 对照组术后气胸1例, I期压疮3例, 心律失常5例, 呼吸困难1例, 切口感染5例, 死亡1例。结论 同期双侧肺叶切除围手术期实施精细化护理干预, 能缩短患者引流管留置时间和术后平均住院日, 对促进患者术后康复具有积极意义。

Phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen worldwide

ABSTRACTAlthough rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended

Neutrophil infiltration leads to fetal growth restriction by impairing the placental vasculature in DENV-infected pregnant miceResearch in context

Summary: Background: Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown. Methods: The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1−/−) mice. The histopathological changes in the placentas were analyzed by morphological techniques. A mouse inflammation array was used to detect the cytokine and chemokine profiles in the serum and placenta. The infiltration characteristics of inflammatory cells in the placentas were evaluated by single-cell RNA sequencing. Findings: Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae. Interpretation: Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection. Funding: The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.)

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.

ObjectivesWe assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients.MethodsA total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis.ResultsWe showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p &lt; 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3.ConclusionUsing serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients