Pooled sputum testing by Xpert® MTB/RIF Ultra for active tuberculosis case finding among high-risk groups in a low-incidence area: a prospective study.

BACKGROUND: Early detection and treatment of tuberculosis (TB) are of great importance to stop its spread. However, optimising the active case findingstrategy is critical to improving its feasibility in regions where TB is epidemic. METHOD: The different pooled ratios between TB-positive and TB-negative sputum specimens were evaluated and a pooling ratio of 5:1 was used for the active case finding screening by Xpert MTB/RIF Ultra among high-risk groups in Beijing. RESULTS: The sensitivity of pooling ratio at 5:1 was 97.5% (39/40). Between October 2022 and March 2023, among 17,681 participants, 1729 metthe active case finding criteria and were screened by 350 5:1 sputum pools by Xpert MTB/RIF Ultra. Four pools (1.1%) tested positive and were further confirmed as definite active TB cases. In our study population with high TB incidence (231/100,000), the cost for detection of individual patients was reduced by 77.4% at a 5:1 pooling ratio. CONCLUSIONS: pooled sputum testing at a suitable ratio using Xpert MTB/RIF Ultra provides a rapid, efficient, and cost-effective method for active TB case finding among high-risk groups in a low-incidence area.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Accuracy of Xpert® MTB/RIF Ultra test for posterior oropharyngeal saliva for the diagnosis of paucibacillary pulmonary tuberculosis: a prospective multicenter study.

BACKGROUND: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. METHODS: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. FINDINGS: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8-83.8] and 56.4% (95% CI: 49.7-62.9), respectively; the specificities were 96.6% (95% CI: 94.3-98.1) for X-Ultra and 97.6 (95CI: 95.5-98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5-61.2; 193/345) and 40.0% (95% CI: 34.8-45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. CONCLUSIONS: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

Metal-phenolic networks acted as a novel bio-filler of a barrier membrane to improve guided bone regeneration via manipulating osteoimmunomodulation.

A guided bone tissue regeneration membrane (GBRM) is traditionally viewed as an inert physical barrier to isolate soft tissue from the bone defect area. However, as a "foreign body", the implantation of a GBRM would inevitably modulate immune response and subsequently affect bone dynamics. Herein, we developed strontium ion (Sr2+)-based metal-phenolic network complexes (MPNs) as a novel type of bio-filler to manipulate the osteoimmunomodulation of the advanced GBRM. For controllable delivery of Sr2+ depending on the difference in affinity between phenolic ligands and Sr2+, tannic acid (TA), epigallocatechin gallate (EGCG), and epigallocatechin (EGC) were selected to chelate with Sr2+. The formed MPNs were incorporated into PCL nanofibrous membranes by blending electrospinning. Among them, TA/Sr based MPN particles displayed the most sustainable release profile of phenolic ligands and Sr2+. Further investigations demonstrated that Sr2+ could not only directly promote osteogenic differentiation of BMSCs, but also manipulate an anti-inflammatory osteoimmune microenvironment in a synergistic manner with TA, thus enhancing osteogenesis and inhibiting bone resorption. The rat alveolar bone defect model also confirmed that the TA/Sr nanoparticle modified membrane displayed better bone regeneration performance than the pure PCL membrane via inhibiting bone resorption. This work provides a new platform for controllable delivery of bioactive nutrient elements, and holds great promise for advancing multi-functional biocomposites.

An Efficient Time-Domain End-to-End Single-Channel Bird Sound Separation Network.

Bird sounds have obvious characteristics per species, and they are an important way for birds to communicate and transmit information. However, the recorded bird sounds in the field are usually mixed, which making it challenging to identify different bird species and to perform associated tasks. In this study, based on the supervised learning framework, we propose a bird sound separation network, a dual-path tiny transformer network, to directly perform end-to-end mixed species bird sound separation in the time-domain. This separation network is mainly composed of the dual-path network and the simplified transformer structure, which greatly reduces the computational resources required of the network. Experimental results show that our proposed separation network has good separation performance (SI-SNRi reaches 19.3 dB and SDRi reaches 20.1 dB), but compared with DPRNN and DPTNet, its parameters and floating point operations are greatly reduced, which means a higher separation efficiency and faster separation speed. The good separation performance and high separation efficiency indicate that our proposed separation network is valuable for distinguishing individual birds and studying the interaction between individual birds, as well as for realizing the automatic identification of bird species on a variety of mobile devices or edge computing devices.

A Pooling Strategy for Detecting Carbapenem Resistance Genes by the Xpert Carba-R Test in Rectal Swab Specimens.

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from individual specimens when positive pools were subsequently retested. All individual specimens in the 61 negative pools were retested as negative by Carba-R. Among the 34 Carba-R-positive samples, 30 and four were positive and negative, respectively, by culture and sequencing. The remaining 381 Carba-R-negative specimens were also negative by culture and sequencing. Overall sensitivity, specificity, positive predictive value, and negative predictive value of the 5:1 pooled screening were 100.0% (95% confidence interval [CI] = 85.9% to 100%), 99.0% (95% CI = 97.2% to 99.7%), 88.2% (95% CI = 71.6% to 96.2%), and 100.0% (95% CI = 98.8% to 100%), respectively. Using the 5:1 pooling strategy, our study completed CRG screening in 414 patients with 193 reagents with significant cost savings. The 5:1 pooling strategy using the Carba-R test showed a potential method for screening CRG from rectal swabs with good sensitivity and decreased cost.

Unidirectional vortex waveguides and multistable vortex pairs in polariton condensates.

Vortices carrying quantized topological charges have potential applications in information processing. In this work, we investigate vortex carriers and waveguides in microcavity polariton condensates, nonresonantly excited by a homogeneous pump with intensity grooves. An intensity groove with a ring shape in the pump gives rise to dark-ring states of the condensate with a π-phase jump, akin to dark solitons. The dark-ring states can be destroyed by a stronger density of the surrounding condensate and reduce into vortex-antivortex pairs. Multiple vortex-pair states are found to be stable in the same dark ring of the pump. When the pump ring is broader, higher-order dark states with multiple π-phase jumps can be obtained, and interestingly they can be used to construct vortex waveguides. If a single vortex is imprinted in such waveguides, it can travel in a particular direction, showing one-way transportation. In other words, an imprinted vortex with a certain charge in a specifically designed higher-order dark state is only allowed to propagate unidirectionally.

Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine.

Implanted bone scaffolds or their biodegradation products may disturb the sequential functions of distinct macrophage phenotypes and cause improper timing of macrophage activation, resulting in delayed or dysfunctional bone regeneration. Although spatiotemporal manipulation of the immune response has been recognized as a promising strategy to address this issue, developing satisfactory drug delivery systems with the function of proper timing control on the macrophage phenotype transformation from pro-inflammatory M1 to anti-inflammatory M2 phenotype still remains a challenge. Here, we propose an amphiphilic nanomedicine with dual anti-inflammatory functions and inflammation-responsive drug release properties to spatiotemporally manage the osteoimmunomodulation of the bone scaffold. The nanomedicine enables the modified scaffold to manipulate the immune response in a staged manner, not only avoiding the overinhibition of M1 macrophages in the initial phase but also facilitating its polarization to M2 phenotype, as well as exhibiting full-course inhibition on later biodegradation-induced inflammation. The described immunomodulatory manner attempts to conform to the principle of osteoimmunomodulation, consequently resulting in better in vivo osteogenesis compared with traditional drug delivery systems. We anticipate that this strategy might aid the development of advanced immunomodulatory bone biomaterials.

Parallel Validation of the NG-Test Carba 5 and the Xpert Carba-R for Detection and Characterization of Carbapenem-Resistant Enterobacterales Causing Bloodstream Infections.

The rapid detection and characterization of carbapenemases in isolates of Enterobacterales are crucial for precise antibiotic administration and infection control. This article reports the findings from a parallel evaluation of the NG-Test Carba 5 (NG Biotech, Guipry, France) and Xpert Carba-R (Cepheid, Sunnyvale, CA) assays in the detection and differentiation of five carbapenemases [imipenem-resistant phenotype (IMP), Klebsiella pneumoniae carbapenemase, New Delhi metallo-ß-lactamase (NDM), oxacillin-hydrolyzing ß-lactamase (OXA)-48-like, and Verona integron-encoded metallo-ß-lactamase] or the genes that encode them. A total of 122 isolates recovered from blood cultures and 106 positive blood culture broth (BCB) specimens, including 134 Klebsiella pneumoniae, 54 Escherichia coli, 27 Enterobacter cloacae, 8 Klebsiella oxytoca, 2 Klebsiella aerogenes, and 3 Citrobacter freundii, were collected from two tertiary hospitals (Xi'an, China). Using PCR sequencing techniques, 89 isolates and 29 BCB specimens were determined to be Enterobacterales harboring carbapenem-resistance genes. In comparison to the PCR sequencing results, the specificities with both the NG-Test Carba 5 and Xpert Carba-R assays were 100%; the sensitivities were 92.1% and 100%, respectively, for recovered isolates and 79.3% and 100% for BCB specimens. The NG-Test Carba 5 missed eight NDM, four OXA-48-like, and one IMP ß-lactamases in specimens containing two or three carbapenemase types. In summary, the NG-Test Carba 5 assay may yield false-negative results if isolates or BCB specimens contain two or three carbapenemases.

Lipoprotein (a): a promising prognostic biomarker in patients with hepatocellular carcinoma after curative resection.

PURPOSE: This study aimed to explore serum lipoprotein (a) (Lp(a)) levels and investigate their prognostic value in hepatocellular carcinoma (HCC) patients after curative resection. MATERIALS AND METHODS: One cohort of 102 healthy individuals, one cohort of 172 HCC patients, and one cohort of 171 HCC patients undergoing curative resection were studied to evaluate serum Lp(a) levels and their prognostic significance, using Kaplan-Meier curves and log-rank tests. RESULTS: The Lp(a) levels in HCC patients were significantly lower than those in healthy individuals. Furthermore, the levels in HCC patients were significantly associated with recurrence. HCC patients were stratified into high Lp(a) (>20 mg/L) and low Lp(a) (≤20 mg/L) groups, using an optimal cutoff point for the Lp(a) of 20 mg/L. Low Lp(a) levels significantly correlated with tumor recurrence and survival time; HCC patients with low Lp(a) levels had higher recurrence rates and shorter survival time than those with high Lp(a) levels; Lp(a) was an independent prognostic factor for relapse-free survival and overall survival, and retained its prognostic value for α-fetoprotein ≤400 ng/mL and tumor size ≤5 cm subgroups in the training and validation cohorts. CONCLUSION: Lp(a) was a promising and useful marker for assessing and monitoring recurrence and prognosis of patients with HCC, and improving Lp(a) levels may be a promising therapeutic strategy in HCC patients.

Phosphorothioate-Modified AP613-1 Specifically Targets GPC3 when Used for Hepatocellular Carcinoma Cell Imaging.

Glypican-3 (GPC3), the cellular membrane proteoglycan, has been established as a tumor biomarker for early diagnosis of hepatocellular carcinoma (HCC). GPC3 is highly expressed in more than 70% HCC tissues detected by antibody-based histopathological systems. Recently, aptamers, a short single-strand DNA or RNA generated from systematic evolution of ligands by exponential enrichment (SELEX), were reported as potential alternatives in tumor-targeted imaging and diagnosis. In this study, a total of 19 GPC3-bound aptamers were successfully screened by capillary electrophoresis (CE)-SELEX technology. After truncated, AP613-1 was confirmed to specifically target GPC3 with a dissociation constant (KD) of 59.85 nM. When modified with a phosphorothioate linkage, APS613-1 targeted GPC3 with a KD of 15.48 nM and could be used as a specific probe in living Huh7 and PLC/PRF/5 imaging, GPC3-positive cell lines, but not in L02 or A549, two GPC3-negative cell lines. More importantly, Alexa Fluor 750-conjugated APS613-1 could be used as a fluorescent probe to subcutaneous HCC imaging in xenograft nude mice. Our results indicated that modified AP613-1, especially APS613-1, was a potential agent in GPC3-positive tumor imaging for HCC early diagnosis.

Systemic Hepatic-Damage Index for Predicting the Prognosis of Hepatocellular Carcinoma after Curative Resection.

Purpose: We have developed a systemic hepatic-damage index (SHI) based on serum total cholesterol (TC) and high density lipoprotein levels (HDL) and determined its prognostic significance in hepatocellular carcinoma (HCC) patients undergoing resection. Experimental Design: The SHI was analyzed in the training cohort of 188 HCC patients and in the validation cohort of 177 HCC patients. The systemic immune-inflammation index (SII) scores in the validation cohorts were also measured. Area under the receiver operating characteristic curve (AUC) was used to explore the prediction accuracy in HCC patients. Results: An optimal cutoff point for the SHI of 2.84 stratified the HCC patients into high SHI (>2.84) and low SHI (≤2.84) groups in the training cohort. Univariate and multivariate analyses revealed the SHI was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative α-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SHI for survival and recurrence were higher than other conventional clinical indices. Low SHI significantly correlated with vascular invasion. The SII scores were significantly higher in patients with low SHI compared with those with high SHI. HCC patients in SHI ≤ 2.84 group had shorter recurrence time and lower survival rate than HCC patients in SHI > 2.84 group. Conclusions: The SHI was a potential biomarker for assessing HCC prognosis, and improving SHI level in HCC patients may be a promising therapeutic strategy decision. The poor outcome in HCC patients with low SHI scores might increase SII scores, increasing the possibility of recurrence and metastasis.

Serum IgG4:IgG Ratio Predicts Recurrence of Patients with Hepatocellular Carcinoma after Curative Resection.

Aim: IgG4 is associated with a Th1-to-Th2 switch, which plays a vital role in metastasis, in patients with malignances; thus, we aimed to investigate its clinical significance in predicting hepatocellular carcinoma (HCC) recurrence in the present study. Methods: The correlation between serum IgG4:IgG ratio and recurrence was analyzed in a cohort of 195 patients undergoing curative resection in 2012. Another 100 patients were analyzed in a prospective independent cohort during 2012-2013 to validate the value of serum IgG4. Serum IgG4 and total IgG concentrations were measured with an automatic immune analyzer and the optimal cutoff value for serum IgG4 levels was determined by X-tile software. Results: Our data revealed that serum IgG4:IgG were significantly elevated in patients with tumor recurrence (P<0.05). A cutoff IgG:IgG4 ratio of 0.08 was set to stratify HCC patients into high (>0.08) and low (≤0.08) groups. High serum IgG4:IgG ratio correlated with significantly shorter time-to-recurrence (median 11.85 months vs. 39.20, P=0.005). Univariate and multivariate analyses demonstrated that serum IgG4:IgG ratio is an independent indicator of tumor recurrence and this retained its clinical significance even in conventional low-recurrence-risk subgroups, including patients with low α-fetoprotein and early-stage diseases. Conclusion: Our results demonstrated that elevated serum IgG4:IgG ratio is associated with poor clinical outcomes in HCC patients and therefore, and can serve as a novel prognostic predictor for HCC patients undergoing resection. Analyzing serum IgG4 would be useful to tailor individualized therapies for patients.

A new use for an old index: preoperative high-density lipoprotein predicts recurrence in patients with hepatocellular carcinoma after curative resections.

BACKGROUND: Hepatocellular carcinoma has high incidence and mortality worldwide. Liver is the site of most metabolic biotransformation, which could reflect the status of cells. Most plasma apolipoproteins, endogenous lipids and lipoproteins are synthesized in the liver. Therefore, the effects of lipid metabolites on prognosis of HCC deserved to be explored. METHODS: We prospectively included 58 healthy donors (HD), 50 chronic hepatitis (CH) patients and a training cohort of 189 patients with HCC who underwent curative resections at Zhongshan Hospital from January 2012 to August 2012. We identified the optimal HDLPO cutoff value at 0.98 mmol/L and used it to stratify patients into low- or high-HDLPO groups for the entire cohort and four low-recurrent-risk subgroups. We also included an independent validation group of 182 HCC patients to validate this cutoff value. Prognostic values of HDLPO and other factors were determined by Kaplan-Meier curves and the Cox proportional hazards model. RESULTS: The low-HDLPO group had a higher median tumor grade (P = 0.020) and a higher recurrence rate (P = 0.032). Results of multivariate analysis showed that preoperative γ-glutamyl transpeptidase (GGT) and HDLPO were independent predictors of recurrence. Moreover, the predictive value of HDLPO was retained in four low-recurrent-risk subgroups. As expected, clinicopathologic characteristics and predictive values were similar in the validation and training cohorts. CONCLUSIONS: HDLPO is an accessible predictor of HCC recurrence after liver resections that can help identify patients who need more careful monitoring and follow-up care.

Circulating CD14+ HLA-DR-/low myeloid-derived suppressor cells predicted early recurrence of hepatocellular carcinoma after surgery.

AIM: Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) in patients undergoing curative resection. METHODS: Myeloid-derived suppressor cells were measured by flow cytometry. The correlation between MDSCs and tumor recurrence was analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015. Prognostic significance was further assessed using Kaplan-Meier survival estimates and log-rank tests. RESULTS: In vivo, CD14+ HLA-DR-/low MDSCs inhibit T cell proliferation and secretion. The frequency of CD14+ HLA-DR-/low MDSCs was significantly higher in HCC patients (3.7 ± 5.3%, n = 183) than in chronic hepatitis patients (1.4 ± 0.6%, n = 25) and healthy controls (1.1 ± 0.5%, n = 50). High frequency of MDSCs was significantly correlated with recurrence (time to recurrence) (P < 0.001) and overall survival (P = 0.034). Patients with HCC in the high MDSC group were prone to more vascular invasion (P = 0.018) and high systemic immune-inflammation index (SII) (P = 0.009) than those in the low MDSC group. Scatter-plot analyses revealed a significant positive correlation between the SII level and the frequency of MDSCs (r = 0.188, P = 0.011). Patients with HCC with a high MDSC frequency and high SII level had significantly shorter time to recurrence (P < 0.001) and overall survival (P = 0.028) than those with a low MDSC frequency and low SII. CONCLUSIONS: An increased frequency of MDSCs was correlated with early recurrence and predicted the prognosis of patients with HCC undergoing curative resection. The HCC patients with high frequency of MDSCs should be provided more advanced management and frequent monitoring.

Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.

As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.

Application of the albumin-bilirubin grade for predicting prognosis after curative resection of patients with early-stage hepatocellular carcinoma.

BACKGROUND: Patients with Barcelona Clinic Liver Cancer (BCLC) 0+A are considered to have early-stage hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) grade is a significant predictor of overall survival (OS) for HCC. However, data are lacking to support its significance for patients with early-HCC. METHODS: We recruited 318 patients with early-HCC who underwent curative resection between January 2012 and August 2013. The Kaplan-Meier method and log-rank tests were used to compare OS of patients with different ALBI grades. Cox regression analysis was applied to evaluate ALBI grade as an independent predictor of OS. RESULTS: Early-HCC patients with ALBI grade II experienced significantly shorter OS (p<0.001) and higher death rates. In the Child-Pugh (C-P) grade-A group, patients with ALBI grade I had a more favorable prognosis than those with grade II (p<0.001), while the C-P grade did not distinguish patients with poor prognosis from the entire group. Cox regression analysis demonstrated that ALBI grade was the most significant independent predictor of OS, and the ALBI grade retained its clinical significance in low α-fetoprotein subgroup. CONCLUSION: ALBI grade predicted OS in patients with early-HCC. Reclassification of C-P grade according to ALBI grade might improve the management of HCC.

Dynamic change of the systemic immune inflammation index predicts the prognosis of patients with hepatocellular carcinoma after curative resection.

BACKGROUND: The aim of the study was to determine the utility of the dynamic change and serial monitoring of the systemic immune inflammation index (SII), which was based on the numbers of patients' lymphocytes (L), platelets (P), neutrophils (N) and defined as P*N/L, for predicting prognosis of patients with hepatocellular carcinoma (HCC) after curative resection. METHODS: We conducted a prospective study of 163 patients with HCC who underwent curative resection at Zhongshan Hospital from January 2012 to May 2013. SII was calculated using data acquired before and approximately 1 month after surgery. An optimal cutoff value stratified patients into groups with high or low SII. Patients were classified into unfavorable and favorable groups using the dynamic change of the SII. Two groups that were further divided into four categories within the entire cohort and the low-risk subgroups were serially monitored for ≥6 months. Prognostic values of the SII and other factors were determined using the Kaplan-Meier method, the Cox proportional hazards model, and the receiver operating characteristics (ROC) curve. RESULTS: The favorable group was likely to have cirrhosis, and the unfavorable group was likely to have larger tumors and a higher recurrence rate. Multivariate analysis revealed that tumor size and dynamic change of the SII were independent risk factors for early recurrence. Moreover, the predictive value of the SII was retained in α-fetoprotein (AFP)-negative and HBeAg-negative-HBV-DNA <2000 IU/mL subgroups. Further, the serial changes of the SII for recurrence and no recurrence groups were statistically significant. CONCLUSIONS: The dynamic change and serial monitoring of the SII represent new indicators for predicting the early recurrence of HCC determining advance optimal therapy in advance.

A simple fluorescent off-on probe for the discrimination of cysteine from glutathione.

A simple and stable fluorescent off-on probe for discrimination of cysteine (Cys) from glutathione (GSH) has been developed by combining resorufin with 7-nitrobenzofurazan. The probe, displaying distinct emission patterns for Cys and GSH at just one excitation wavelength, can be used for simultaneous determination of Cys and GSH in human plasma.

Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.

1. Cytochrome P450 2D (CYP2D) protein is widely expressed across brain regions in human and rodents. We investigated the interactions between tramadol, a clinically used analgesic, and brain CYP2D regulators, by establishing concentration-time curves of tramadol and O-desmethyltramadol (M1) in rat cerebrospinal fluid (CSF) and plasma, as well as by analyzing the analgesia-time course of tramadol. 2. Propranolol (20 µg, intracerebroventricular injection), CYP2D inhibitor, prolonged the elimination t1/2 of tramadol (40 mg/kg, intraperitoneal injection) in the CSF; meanwhile, lower Cmax and AUC0-∞ values of M1 were observed. Nicotine (1 mg base/kg, subcutaneous injection, seven days), brain CYP2D inducer, induced a shorter Tmax and elevated Cmax of M1 in CSF. No differences in the peripheral metabolism of tramadol were observed following propranolol and nicotine pretreatment. Nicotine increased areas under the analgesia-time curve (AUC) for 0-45 min and 0-90 min of tramadol, which was attenuated by propranolol administration. The analgesic actions of tramadol positively correlated with cerebral M1 concentration. 3. The results suggest that the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions (DDIs) of tramadol. Brain CYPs may play an important role in DDIs of centrally active substances.