Long-term oral administration of Huaier granules improves survival outcomes in hepatocellular carcinoma patients within Milan criteria following microwave ablation: a propensity score matching and stabilized inverse probability weighting analysis.

Objective: This study aimed to elucidate the therapeutic effects of Huaier granules on hepatocellular carcinoma (HCC) within the Milan criteria in patients who underwent microwave ablation (MWA). Materials and methods: A total of 228 patients were included, with 97 in the Huaier group and 131 in the control group. We evaluated progression-free survival (PFS), overall survival (OS), and extrahepatic metastasis survival (EMS) using Kaplan-Meier (KM) curves with a log-rank test. Propensity Score Matching (PSM) and Stabilized Inverse Probability of Treatment Weighting (IPTW) were performed to minimize selection and confounding biases. Results: Following PSM, the 1-, 3-, and 5-year PFS rates in the Huaier and control groups were 83.5% vs 70.7%, 57.7% vs 42.6%, and 43.6% vs 31.9% (p = 0.030), respectively. The 1-, 3-, and 5-year OS rates were 98.9% vs 95.6%, 83.9% vs 72.3%, and 72.2% vs 53.7% (p = 0.023), respectively. The corresponding 1-, 3-, and 5-year EMS rates were 98.9% vs 93.4%, 91.7% vs 83.7%, and 91.7% vs 78.5% (p = 0.039), respectively. Stabilized IPTW analysis of KM curves yielded results similar to those of the PSM analysis. Additionally, administering Huaier granules for at least 6 months significantly improved PFS and OS. Conclusion: Huaier granules can reduce the risk of recurrence and improve the OS of patients with HCC within the Milan criteria following MWA. Administering Huaier granules for over 6 months proved beneficial.

Predictive nomograms based on gamma-glutamyl transpeptidase to prealbumin ratio for prognosis of hepatocellular carcinoma patients without microvascular invasion.

BACKGROUND: Hepatocellular carcinoma (HCC) presents a significant threat to individuals and healthcare systems due to its high recurrence rate. Accurate prognostic models are essential for improving patient outcomes. Gamma-glutamyl transpeptidase (GGT) and prealbumin (PA) are biomarkers closely related to HCC. This study aimed to investigate the predictive value of the GGT to PA ratio (GPR) and to construct prognostic nomograms for HCC patients without microvascular invasion. METHODS: We retrospectively analyzed data from 355 HCC patients who underwent radical hepatectomy at Shengjing Hospital of China Medical University between December 2012 and January 2021. Patients were randomly assigned to a training cohort (n = 267) and a validation cohort (n = 88). The linearity of GPR was assessed using restricted cubic spline (RCS) analysis, and the optimal cut-off value was determined by X-tile. Kaplan-Meier survival curves and log-rank tests were used to investigate the associations between GPR and both progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis identified independent risk factors, enabling the construction of nomograms. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the accuracy of the nomograms. Decision curve analysis (DCA) assessed the predictive value of the models. RESULTS: Patients were categorized into GPR-low and GPR-high groups based on a GPR value of 333.33. Significant differences in PFS and OS were observed between the two groups (both P < 0.001). Cox multivariate analysis identified GPR as an independent risk factor for both PFS (OR = 1.80, 95% CI: 1.24-2.60, P = 0.002) and OS (OR = 1.87, 95% CI: 1.07-3.26, P = 0.029). The nomograms demonstrated good predictive performance, with C-index values of 0.69 for PFS and 0.76 for OS. Time-dependent ROC curves and calibration curves revealed the accuracy of the models in both the training and validation cohorts, with DCA results indicating notable clinical value. CONCLUSIONS: GPR emerged as an independent risk factor for both OS and PFS in HCC patients without microvascular invasion. The nomograms based on GPR demonstrated relatively robust predictive efficiency for prognosis.

Aquaporin ZmTIP2;3 Promotes Drought Resistance of Maize through Symbiosis with Arbuscular Mycorrhizal Fungi.

Arbuscular mycorrhizal fungi symbiosis plays important roles in enhancing plant tolerance to biotic and abiotic stresses. Aquaporins have also been linked to improved drought tolerance in plants and the regulation of water transport. However, the mechanisms that underlie this association remain to be further explored. In this study, we found that arbuscular mycorrhiza fungi symbiosis could induce the gene expression of the aquaporin ZmTIP2;3 in maize roots. Moreover, compared with the wild-type plants, the maize zmtip2;3 mutant also showed a lower total biomass, colonization rate, relative water content, and POD and SOD activities after arbuscular mycorrhiza fungi symbiosis under drought stress. qRT-PCR assays revealed reduced expression levels of stress genes including LEA3, P5CS4, and NECD1 in the maize zmtip2;3 mutant. Taken together, these data suggest that ZmTIP2;3 plays an important role in promoting maize tolerance to drought stress during arbuscular mycorrhiza fungi symbiosis.

The tumor burden score may be a discriminator in microwave ablation versus liver resection for hepatocellular carcinoma within the Milan criteria: a propensity score matching and inverse probability of treatment weighting study.

Purpose: This study aims to compare the prognostic outcome of resection (RES) and microwave ablation (MWA) in different tumor burden score (TBS) cohorts. Patients and Methods: We retrospectively analyzed 479 patients with primary hepatocellular carcinoma (HCC) who underwent RES (n = 329) or MWA (n = 150) with curative intent at our institution. We assessed their overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier curve. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to minimize selection and confounding biases. Multivariate Cox regression was used to define the association between surgical modalities and outcomes. Results: Following PSM, in the TBS ≤3 cohort, the cumulative 1-, 3-, 5- year OS in the RES and MWA groups were 92.5% vs. 98.8%, 82.7% vs. 90.0%, and 82.7% vs. 83.2% (P = 0.366), respectively. The corresponding PFS rates in the RES and MWA groups were 82.7% vs. 88.0%, 63.6% vs. 68.3% and 55.2% vs. 56.3, respectively (P = 0.218). In the TBS >3 cohort, the cumulative 1-, 3-, 5- year OS between the RES and MWA groups were 92.5% vs. 95.0%, 82.8% vs. 73.2% and 76.3% vs. 55.1%, (P = 0.034), respectively. The corresponding PFS rates in the RES and MWA groups were 78.0% vs. 67.5%, 63.6% vs. 37.5% and 55.2% vs. 37.1%, respectively (P = 0.044). The IPTW analysis showed similar results as shown in PSM analysis. The multivariate Cox regression indicated that the type of surgical modality was not associated with a poorer prognostic outcome in the TBS ≤3 cohort, unlike in the TBS >3 cohort. Conclusion: TBS, as a discriminator, might help guide treatment decision-making for HCC within the Milan criteria.

An Easy-to-Use Nomogram Based on SII and SIRI to Predict in-Hospital Mortality Risk in Elderly Patients with Acute Myocardial Infarction.

Aim: Inflammatory response is closely associated with poor prognosis in elderly patients with acute myocardial infarction (AMI). The aim of this study was to develop an easy-to-use predictive model based on medical history data at admission, systemic immune inflammatory index (SII), and systemic inflammatory response index (SIRI) to predict the risk of in-hospital mortality in elderly patients with AMI. Methods: We enrolled 1550 elderly AMI patients (aged ≥60 years) with complete medical history data and randomized them 5:5 to the training and validation cohorts. Univariate and multivariate logistic regression analyses were used to screen risk factors associated with outcome events (in-hospital death) and to establish a nomogram. The discrimination, calibration, and clinical application value of nomogram were evaluated based on receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Results: The results of multivariate logistic regression showed that age, body mass index (BMI), previous stroke, diabetes, SII, and SIRI were associated with in-hospital death, and these indicators will be included in the final prediction model, which can be obtained by asking the patient's medical history and blood routine examination in the early stage of admission and can improve the utilization rate of the prediction model. The areas under the ROC curve for the training and validation cohorts nomogram were 0.824 (95% CI 0.796 to 0.851) and 0.809 (95% CI 0.780 to 0.836), respectively. Calibration curves and DCA showed that nomogram could better predict the risk of in-hospital mortality in elderly patients with AMI. Conclusion: The nomogram constructed by combining SII, SIRI, and partial medical history data (age, BMI, previous stroke, and diabetes) at admission has a good predictive effect on the risk of in-hospital death in elderly patients with AMI.

LjAMT2;2 Promotes Ammonium Nitrogen Transport during Arbuscular Mycorrhizal Fungi Symbiosis in Lotus japonicus.

Arbuscular mycorrhizal fungi (AMF) are important symbiotic microorganisms in soil that engage in symbiotic relationships with legumes, resulting in mycorrhizal symbiosis. Establishment of strong symbiotic relationships between AMF and legumes promotes the absorption of nitrogen by plants. Ammonium nitrogen can be directly utilised by plants following ammonium transport, but there are few reports on ammonium transporters (AMTs) promoting ammonium nitrogen transport during AM symbiosis. Lotus japonicus is a typical legume model plant that hosts AMF. In this study, we analysed the characteristics of the Lotus japonicus ammonium transporter LjAMT2;2, and found that it is a typical ammonium transporter with mycorrhizal-induced and ammonium nitrogen transport-related cis-acting elements in its promoter region. LjAMT2;2 facilitated ammonium transfer in yeast mutant supplement experiments. In the presence of different nitrogen concentrations, the LjAMT2;2 gene was significantly upregulated following inoculation with AMF, and induced by low nitrogen. Overexpression of LjAMT2;2 increased the absorption of ammonium nitrogen, resulting in doubling of nitrogen content in leaves and roots, thus alleviating nitrogen stress and promoting plant growth.

Binding of cyclic diguanylate in the non-catalytic EAL domain of FimX induces a long-range conformational change.

FimX is a multidomain signaling protein required for type IV pilus biogenesis and twitching motility in the opportunistic pathogen Pseudomonas aeruginosa. FimX is localized to the single pole of the bacterial cell, and the unipolar localization is crucial for the correct assembly of type IV pili. FimX contains a non-catalytic EAL domain that lacks cyclic diguanylate (c-di-GMP) phosphodiesterase activity. It was shown that deletion of the EAL domain or mutation of the signature EVL motif affects the unipolar localization of FimX. However, it was not understood how the C-terminal EAL domain could influence protein localization considering that the localization sequence resides in the remote N-terminal region of the protein. Using hydrogen/deuterium exchange-coupled mass spectrometry, we found that the binding of c-di-GMP to the EAL domain triggers a long-range (∼ca. 70 Å) conformational change in the N-terminal REC domain and the adjacent linker. In conjunction with the observation that mutation of the EVL motif of the EAL domain abolishes the binding of c-di-GMP, the hydrogen/deuterium exchange results provide a molecular explanation for the mediation of protein localization and type IV pilus biogenesis by c-di-GMP through a remarkable allosteric regulation mechanism.