Investigation of the correlation between platelet antibodies and peripheral blood cytopenia in patients with hepatocellular carcinoma.

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.

Efficacy and safety of Lenvatinib-based combination therapies for patients with unresectable hepatocellular carcinoma: a single center retrospective study.

Background: Reports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies. Methods: This was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR). Results: Of 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, P=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE. Conclusion: Our study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.

Synergy of Adsorption and Photocatalytic Reduction for Efficient Removal of Cr(VI) with Polyvinylidene Fluoride@Polyvinyl Alcohol-FeC2O4/Bi2.15WO6.

Although the photocatalytic reduction of Cr(VI) to Cr(III) by traditional powder photocatalysts is a promising method, the difficulty and poor recovery of photocatalysts from water hinder their wide practical applications. Herein, we present that FeC2O4/Bi2.15WO6 (FeC2O4/BWO) composites were tightly bonded to modified polyvinylidene fluoride (PVDF) membranes by chemical grafting with the aid of polyvinyl alcohol (PVA) to form photocatalytic composite membranes (PVDF@PVA-FeC2O4/BWO). The contact angle of PVDF@PVA-FeC2O4/BWO (0.06 wt % of FeC2O4/BWO) is 48.0°, which is much lower than that of the pure PVDF membrane (80.5°). Meanwhile, the permeate flux of 61.43 g m-2 h-1 and water flux of 250.60 L m-2 h-1 were observed for PVDF@PVA-FeC2O4/BWO composite membranes. The tensile strength of composite membranes reached 48.84 MPa, which was 9.8 times higher than that of PVDF membrane. It was found that the PVDF@PVA-FeC2O4/BWO membrane exhibited excellent photocatalytic Cr(VI) reduction performance under both simulated and real sunlight irradiation. The adsorption for Cr(VI) by PVDF@PVA-FeC2O4/BWO can reach 47.6% in the dark process within 30 min, and the removal percentage of Cr(VI) could reach 100% with a rate constant k value of 0.2651 min-1 after 10 min of light exposure, indicating a synergistic effect of adsorption and photoreduction for Cr(VI) removal by the composite membrane. The PVDF@PVA-FeC2O4/BWO membrane had good stability and reusability after seven consecutive cycles. Most importantly, the influences of foreign ions on Cr(VI) reduction were investigated to mimic real sewage, which revealed that no obvious adverse effects can be found with the presence of common foreign ions in sewage. The photocatalytic membrane material developed in this study provides a new idea for treating Cr(VI)-containing wastewater and has a more significant application prospect.

Highly Efficient Luminescence from a Red Thermally Activated Delayed Fluorescence Emitter with Flexible Conformation of Ancillary Groups.

Robust scaffolds were typically applied in thermally activated delayed fluorescence (TADF) molecules to suppress the non-radiative decay, trigger the fast spin-flipping, and enhance the light out-coupling efficiency. Herein, we disclosed for the first time the positive effect of flexible conformation of ancillary groups on the photophysical properties of TADF emitter. The red TADF emitter Ph-TPA with flexible conformation demonstrated small excited-state structural distortion and low reorganization energy compared to the counterpart Mc-TPA with a rigid macrocycle. Consequently, Ph-TPA showed an excellent photoluminescent quantum yield (PLQY) of 92 % and a state-of-the-art external quantum efficiency (EQE) of 30.6 % at 630 nm. This work could deepen our understanding of structure-property relationships of organic luminophores and help us to rationalize the design of efficient TADF materials.

QTL-seq and transcriptomic integrative analyses reveal two positively regulated genes that control the low-temperature germination ability of MTP-maize introgression lines.

KEY MESSAGE: Two candidate genes (ZmbZIP113 and ZmTSAH1) controlling low-temperature germination ability were identified by QTL-seq and integrative transcriptomic analyses. The functional verification results showed that two candidate genes positively regulated the low-temperature germination ability of IB030. Low-temperature conditions cause slow maize (Zea mays L.) seed metabolism, resulting in slow seedling emergence and irregular seedling emergence, which can cause serious yield loss. Thus, improving a maize cultivar's low-temperature germination ability (LTGA) is vital for increasing yield production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant of cold stress and can thus be used to improve the LTGA of maize. In a previous study, the genetic bridge MTP was constructed (from maize, T. dactyloides, and Z. perennis) and used to obtain a highly LTGA maize introgression line (IB030) by backcross breeding. In this study, IB030 (Strong-LTGA) and Mo17 (Weak-LTGA) were selected as parents to construct an F2 offspring. Additionally, two major QTLs (qCS1-1 and qCS10-1) were mapped. Then, RNA-seq was performed using seeds of IB030 and the recurrent parent B73 treated at 10 °C for 27 days and 25 °C for 7 days, respectively, and two candidate genes (ZmbZIP113 and ZmTSAH1) controlling LTGA were located using QTL-seq and integrative transcriptomic analyses. The functional verification results showed that the two candidate genes positively regulated LTGA of IB030. Notably, homologous cloning showed that the source of variation in both candidate genes was the stable inheritance of introgressed alleles from Z. perennis. This study was thus able to analyze the LTGA mechanism of IB030 and identify resistance genes for genetic improvement in maize, and it proved that using MTP genetic bridge confers desirable traits or phenotypes of Z. perennis and tripsacum essential to maize breeding systems.

Prognostic Analysis of Single Large Hepatocellular Carcinoma Following Radical Resection: A Single-Center Study.

Objective: To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection. Methods: Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors. Results: A total of 485 cases were included. The average age was 51.2±11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8±3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥17.1 µmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) >60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) >225 U/L (HR=1.442, P=0.007), blood loss ≥400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P<0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT >60 U/L (HR=1.512, P=0.003), LDH >225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659-0.724) and 0.659 (95% CI: 0.623-0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms. Conclusion: Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥17.1 µmol/L, GGT>60 U/L, LDH>225 U/L, blood loss≥400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.

Moving to a healthier city? An analysis from China's internal population migration.

A healthy urban environment is considered as an important issue for the amenity and equity of migrants. China has one of the largest internal population movements in the world, and the environmental health of its migrants becomes a growing concern. Based on the 1‰ microdata from the 2015 1% population sample survey, this study uses the spatial visualization and spatial econometric interaction model to reveal intercity population migration patterns and the role of environmental health in China. The results are as follows. First, the main direction of population migration is toward economically developed high class cities, especially the eastern coast where the intercity population migration is most active. However, these major destinations are not necessarily the healthiest areas for the environment. Second, environmentally friendly cities are mainly located in the southern region. Among them, the areas with less serious atmospheric pollution are mainly distributed in the south, climate comfort zones are mainly located in the southeastern region, but areas with more urban green space are mainly distributed in the northwestern region. Third, compared with socioeconomic factors, environmental health factors have not yet become a major driver of population migration. Migrants often place higher value on income than on environmental health. The government should focus not only on the public service wellbeing of migrant workers, but also on their environmental health vulnerability.

QTL Mapping and a Transcriptome Integrative Analysis Uncover the Candidate Genes That Control the Cold Tolerance of Maize Introgression Lines at the Seedling Stage.

Chilling injury owing to low temperatures severely affects the growth and development of maize (Zea mays.L) seedlings during the early and late spring seasons. The existing maize germplasm is deficient in the resources required to improve maize's ability to tolerate cold injury. Therefore, it is crucial to introduce and identify excellent gene/QTLs that confer cold tolerance to maize for sustainable crop production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant to cold and can be used to improve the cold tolerance of maize. In a previous study, a genetic bridge among maize that utilized Z. perennis and T. dactyloides was created and used to obtain a highly cold-tolerant maize introgression line (MIL)-IB030 by backcross breeding. In this study, two candidate genes that control relative electrical conductivity were located on MIL-IB030 by forward genetics combined with a weighted gene co-expression network analysis. The results of the phenotypic, genotypic, gene expression, and functional verification suggest that two candidate genes positively regulate cold tolerance in MIL-IB030 and could be used to improve the cold tolerance of cultivated maize. This study provides a workable route to introduce and mine excellent genes/QTLs to improve the cold tolerance of maize and also lays a theoretical and practical foundation to improve cultivated maize against low-temperature stress.

Using azaacene as an acceptor unit to construct an ultraefficient red fluorophore with an EQE over 40.

Azaacenes, which have been known for a long time, are of scientific and practical importance in organic electronics. Azaacenes once shone as the luminophore in organic light-emitting diodes (OLEDs). However, due to the low exciton utilization efficiency and/or the aggregation induced quenching (ACQ) effect, N-heteroacene based OLEDs generally showed inferior device performance. In this work, azaacene has been revisited and applied as an acceptor for a red fluorophore (AZA-TPA), where the judicious connection pattern between donor and acceptor maximized the harvest of singlet and triplet excitons, resulting in a high photoluminescence efficiency of 94.6% in doped films (3 wt%). In addition, the linearly-fused polycyclic structure contributed to a high horizontal emitting dipole ratio (Θ‖ = 90%). As a result, an AZA-TPA-based OLED achieved an unprecedented external quantum efficiency of 41.30% at 610 nm. This work will pave a new path for the development of efficient N-heteroacene-based fluorophores.

Intramolecular charge transfer effect for highly efficient deep red and near infrared thermally activated delayed fluorescence.

Thermally activated delayed fluorescence (TADF) materials with emission in the deep red and near infrared (DR/NIR) region are underresearched due to the limited choice of strong donor/acceptor units. The current mainstream strategy for the design of DR/NIR TADFs is to increase the acceptor strength via the introduction of multiple sub-acceptor units, thereby narrowing the bandgap. In this work, the intramolecular charge transfer (ICT) effect was applied for the development of acceptor units to achieve efficient DR/NIR TADFs. The ICT effect within the acceptor unit enhanced the π-electron delocalization, lowered the LUMO and redshifted the emission wavelength. In addition, the fusion of the donor unit into the planar acceptor skeleton rigidified the molecular structure and reduced the non-radiative decay. This proof-of-concept study demonstrated that ICT is an undoubtedly effective strategy for the rational design of efficient DR/NIR TADFs.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients.

BACKGROUND: Early singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features. METHODS: We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models. RESULTS: Our RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort. CONCLUSIONS: Compared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients' outcomes.

Primary hepatic paraganglioma mimicking hepatocellular carcinoma: a case report.

Background: Primary hepatic paraganglioma (HPGL) originates from sympathetic nervous tissue in the liver. It is one of an exceedingly rare kind of sympathetic paragangliomas. The radiological features and clinical characters of HPGL can be easily confused with hepatocellular carcinoma (HCC). We present a case of HCC that was preoperatively diagnosed as hepatic paraganglioma, however, was pathologically verified as hepatic paraganglioma after surgery. Case Description: The present case reported a 47-year-old female with a very rare HPGL without any clinical symptoms, except for hyper menorrhagia and paroxysmal hypertension. The Spiegelman lobe of the liver underwent hepatic magnetic resonance imaging, which revealed a 3.2×3.8 cm mass, with uneven arterial phase wash-in and rapid portal and delayed phase wash-out. According to the imaging results, the patient was first diagnosed with hepatocellular carcinoma, and a radical hepatectomy was performed. However, the blood pressure of the patient displayed dramatic changes when the tumor was stimulated in operation. There were no substantial abnormalities found in the bilateral renal and adrenal glands. Therefore, we presumed that the tumor was related to functional pheochromocytoma. The tumor tissue was shown to be positive for chromogranin A, synaptophysin, CD56, and vimentin by immunohistochemical analysis. As a result, the patient was diagnosed with HPGL after this pathologic evaluation. Conclusions: There are several similarities between HPGL and HCC. For the treatment of hepatic paraganglioma, surgical excision is the recommended practice. Although the majority of paragangliomas are benign, long-term monitoring is required to differentiate benign from malignant paragangliomas.

One- versus two-stage partial hepatectomy for large resectable solitary hepatocellular carcinomas determined preoperatively to have a narrow resection margin: a propensity score matching analysis.

Background: For patients with a large but resectable solitary hepatocellular carcinoma (HCC) of >5 cm in diameter, it is often difficult to achieve a sufficient resection margin. There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial. Methods: From August 2014 to February 2017, patients with a large but resectable solitary HCC of >5 cm and a preoperative estimated resection margin of <1.0 cm were retrospectively studied. They were divided into one- and two-stage resection groups. A retrospective analysis was performed, followed by propensity score matching (PSM) analysis. Disease recurrence, survival, intraoperative and postoperative data were compared. Results: Before PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.3%, 31.7%, 24.3%, 19.2% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.007). The corresponding OS rates were 61.0%, 45.2%, 43.8%, 38.4% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.029). After PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.0%, 31.5%, 27.3%, 21.0% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.013). The corresponding OS rates were 62.5%, 41.1%, 41.1%, 37.5% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.038). Differences in the resection margins between the one- and two-stage groups before [0.3 (0-0.5) versus 1.2 (0.8-2.2) cm] and after [0.2 (0-0.5) versus 1.2 (0.8-2.2) cm] PSM were also significant. Conclusions: Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of >5 cm, and resulted in significantly better long-term survival outcomes after partial hepatectomy.

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma: a randomized comparative study.

Background: Both portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant (FLR). Methods: This study was a single-center, prospective randomized comparative study. Patients with the diagnosis of hepatitis B related hepatocellular carcinoma (HCC) were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints were tumor resection and three-year overall survival (OS) rates. Results: Between November 2014 to June 2016, 76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n=38) and TACE + PVE groups (n=38). Thirty-seven patients (97.4%) in the ALPPS group compared with 25 patients (65.8%) in the TACE + PVE group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI: 1.17-1.87, P<0.001). The three-year OS rate of the ALPPS group (65.8%) (95% CI: 50.7-80.9) was significantly better than the TACE + PVE group (42.1%) (95% CI: 26.4-57.8) (HR 0.50, 95% CI: 0.26-0.98, two-sided P=0.036). However, no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found (HR 0.80, 95% CI: 0.35-1.83, two-sided P=0.595). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the TACE + PVE group (risk ratio 2.70, 95% CI: 1.17-6.25, P=0.007). Conclusions: ALPPS resulted in significantly better intermediate-term OS outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with TACE + PVE in patients who had initially unresectable HBV-related HCC.

Circulating Tumor Cells Expressing Krüppel-Like Factor 8 and Vimentin as Predictors of Poor Prognosis in Pancreatic Cancer Patients.

BACKGROUND: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). METHODS: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8+ and vimentin+ CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. RESULTS: Patients with CTCs (n = 30) had a higher relapse rate compared to those without (n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8+/vimentin+ CTCs to total CTCs was inversely related to TTR (r = -0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8+/vimentin+ (P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8+/vimentin+ CTCs (both P < 0.05). CONCLUSION: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

Prediction of Patient Survival Following Hepatic Resection in Early-Stage Hepatocellular Carcinoma with Indexed Ratios of Aspartate Aminotransferase to Platelets: A Retrospective Cohort Study.

PURPOSE: To predict patient survival in early-stage hepatocellular carcinoma (HCC) following hepatic resection. We evaluated the prognostic potential of the aspartate aminotransferase to platelet ratio index (APRI) in order to use it to model a nomogram. PATIENTS AND METHODS: We randomized 901 early-stage HCC patients treated with hepatic resection at our center into training and validation cohorts that were followed from January 2009 to December 2012. X-tile software was used to establish the APRI cut-off threshold in the training cohort. The validation cohort was subsequently assessed to determine threshold value accuracy. Data generated from the multivariate analysis in the training cohort were used to design a prognostic nomogram. Decision curve analyses (DCA), concordance index values (C-index) and calibration curves were used to determine the performance of the nomogram. RESULTS: X-tile software revealed that the optimal APRI cut-off threshold in the training cohort that distinguished between patients with different prognoses was 0.9. We, therefore, validated its prognostic value. Multivariate analyses showed that poor overall survival was associated with APRI above 0.9, blood loss of more than 400 mL, liver cirrhosis, multiple tumors, tumor size greater than 5 cm, microvascular invasion and satellite lesions. When the independent risk factors were integrated into the prognostic nomogram, it performed well with accurate predictions. Indeed, the performance was better than comparative prognosticators (P<0.05 for all) with 0.752 as the C-index (95% CI: 0.706-0.798). These results were verified by the validation cohort. CONCLUSION: APRI was a noninvasive and accurate predictive indicator for patients with early-stage HCC. Following hepatic resection to treat early-stage HCC, individualized patient survival predictions can be aided by the nomogram based on APRI.

Dynamic monitoring of serum liver function indexes in patients with COVID-19.

BACKGROUND: Some patients with the novel 2019 coronavirus disease (COVID-19) display elevated liver enzymes. Some antiviral drugs that can be used against COVID-19 are associated with a risk of hepatotoxicity. AIM: To analyze the clinical significance of the dynamic monitoring of the liver function of patients with COVID-19. METHODS: This was a retrospective study of patients diagnosed with COVID-19 in January and February 2020 at the Department of Infection, Shantou Central Hospital. The exclusion criteria for all patients were: (1) History of chronic liver disease; (2) History of kidney disease; (3) History of coronary heart disease; (4) History of malignancy; or (5) History of diabetes. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase, and total bilirubin of patients with COVID-19 were measured on days 1, 3, 7 and 14 after admission, and compared to non-COVID-19 patents. RESULTS: Twelve patients with COVID-19 (seven men and five women) and twelve controls (eight men and four women) were included. There were one, two, and nine patients with severe, mild, and moderate COVID-19, respectively. There were no differences in age and sex between the two groups (both P > 0.05). No significant differences were found in albumin, ALT, AST, γ-glutamyltransferase, or total bilirubin between the controls and the patients with COVID-19 on day 1 of hospitalization (all P > 0.05). Serum albumin showed a decreasing trend from days 0 to 7 of hospitalization, reaching the lowest level on day 7. Total bilirubin was higher on day 3 than on day 7. ALT, AST, and γ-glutamyltransferase did not change significantly over time. The severe patient was observed to have ALT levels of 67 U/L and AST levels of 75 U/L on day 7, ALT of 71 U/L and AST of 35 U/L on day 14, and ALT of 210 U/L and AST of 123 U/L on day 21. CONCLUSION: Changes in serum liver function indicators are not obvious in the early stage of COVID-19, but clinically significant changes might be observed in severe COVID-19.

A High Preoperative Platelet-Lymphocyte Ratio Is a Negative Predictor of Survival After Liver Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma: A Retrospective Study.

Objective: To evaluate the importance of preoperative blood platelet to lymphocyte ratio (PLR) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver surgery and to examine the connection with CD8+ lymph cell infiltration. Methods: Between 2009 and 2014, consecutive HCC patients who received curative liver surgery were included into this retrospective study. Baseline clinicopathological characteristics were analyzed to identify predictors of recurrence-free and overall patient survival rate after liver resection. The samples of all patients were under Tissue Microarray (TMA) construction and immunohistochemical staining for CD8+.The association of the number of CD8+T-cells in the cancer nests and peritumoral stroma with PLR level was analyzed. Results: A total of 1,174 HBV-related HCC patients who received a liver resection without any peri-operative adjuvant therapy were enrolled into this retrospective study. Univariate and Multivariate analysis using Cox regression model showed that PLR was an independent factor affecting recurrence and overall survivals. The optimal cutoff of PLR using the receiver operating characteristic curve was 150. There were 236 patients (20.1%) who had a PLR of 150 or more. The 5-year survival rate after liver resection was 71.8% in patients with a PLR of < 150 and it was 57.2% in those with a PLR of 150 or more (P < 0.001). Both 5-year recurrence-free and overall survival rates in liver cancer stage A patients at Barcelona Clinic with different PLR group were also significantly different (P = 0.007 for recurrence and P = 0.001 for overall survival). Similar results were also observed in stage B patients (P < 0.001 for recurrence and P = 0.033 for overall survival). To determine the association between PLR and the severity of liver inflammation, an immuno-histological examination using CD8+ staining was performed on the liver specimens of 1,174 patients. Compared with low PLR (<150) group, more CD8+T-cells were found in the peritumoral tissue in high PLR (≥ 150) group. Conclusions: PLR played as an independent factor for predicting the survival after hepatectomy for HCC patients. A high PLR was associated with an accumulation of CD8+ T-cells in the peritumoral stroma.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Nomograms to predict the long-time prognosis in patients with alpha-fetoprotein negative hepatocellular carcinoma following radical resection.

BACKGROUND: To develop and validate nomograms that can be used to predict outcomes in individuals suffering alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) after radical resection. METHODS: A total of 509 AFP-negative HCC patients who received hepatectomy between January 2009 and March 2013 in our center were randomized into training and validation cohorts. Nomograms for both overall and recurrence-free survival (OS and RFS, respectively) were established based on the predictors in the training cohort. Nomograms performance and discriminative power were assessed with concordance index (C-index) values and decision curve analyses (DCA). The results were validated in the validation cohort. RESULTS: Alkaline phosphatase, liver cirrhosis, tumor size, satellite lesions, microvascular invasion, and Edmondson-Steiner grade were significantly linked to OS and RFS. Sex and tumor number were additional predictors for RFS. The OS nomogram had a C-index value of 0.742, which was better than that for the AJCC eighth edition (0.632), BCLC system (0.553), and JIS score (0.557) (all P < .001). The RFS nomogram C-index was 0.669, which was also superior to that of the AJCC eighth (0.608), BCLC stage (0.554), JIS score (0.551), and model of Gan et al (0.636) (P < .05 for all). Calibration curves indicated a good agreement between observed actual outcomes and predicted values. Kaplan-Meier curves and DCA indicated that nomograms were powerful in discrimination and clinical usefulness. These results were supported by the validation cohort. CONCLUSIONS: These nomograms presented more accurate prognostic prediction in patients with AFP-negative HCC after hepatectomy.