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68Ga-DOTA-TATE has been successfully applied in the diagnosis of clinical neuroendocrine tumors，but its short half-life limits its widespread use. This study aimed to develop [18F]AlF-NOTA-TATE to meet the clinical demands of patients with neuroendocrine tumors (NETs) for diagnosis and treatment evaluation. A new column chromatography purification method for [18F]AlF-NOTA-TATE was developed and automated synthesis was performed using a clinical single-vessel multi-functional fluorine synthesis module. The lipophilicity, in vitro stability，and pharmacokinetics of [18F]AlF-NOTA-TATE were studied，and biodistribution experiments and PET/CT imaging of nude mice with NCI-H69 (SSTR2 positive expression) small cell lung cancer were conducted，followed by preliminary clinical evaluation on three patients with neuroendocrine tumors. The new column chromatography purification method for [18F]AlF-NOTA-TATE was simple，which was synthesized in a short time with higher than 95% of radiochemical purity and，less than 3% of.ethanol content. Pharmacokinetic and biodistribution experiments in BALB/c mice showed rapid blood clearance of the drug and renal metabolism. PET/CT imaging of tumor-bearing mice showed specific uptake of the radiotracer in SSTR-positive tumors. Preliminary clinical application showed that [18F]AlF-NOTA-TATE is well targeted in patients with long retention time and can provide better image quality. The column chromatography method for the preparation of [18F]AlF-NOTA-TATE was simple and had high radiochemical purity. Preliminary clinical results suggested that [18F]AlF-NOTA-TATE has further value for clinical research.

The present study investigated the effects of heat treatment (solid solution and aging treatments) on the microstructure and mechanical properties of a hot-rolled α+β Ti–3Al–5Mo–4.5V (TC16) produced through blended elemental powder metallurgy (BEPM) process using master alloy hydrogenation (MAH) approach. After solid solution treatment, metastable martensite α'' phase and athermal ω phase were formed. Aging treatment facilitated decomposition of metastable phases and precipitation of αs particles. Dispersion strengthening, resulting from the formation of a significant amount of α/β interfaces between fine secondary αs particles and β matrix, played a decisive role in enhancing the strength of the TC16 alloy. However, elevated aging temperatures promoted the coarsening of αs particles, leading to a reduction in the strengthening effect. A systematic investigation of the effects of the solid solution and aging treatments enabled the evolution of a bimodal microstructure with the precipitation of fine αs particles, contributing to an outstanding combination of strength and ductility. The ultimate tensile strength reached 1424.6 MPa with an elongation at break of 7.7%, while the hardness reached 380.2HV.

The present work proposes a novel master-alloy pre-hydrogenation powder metallurgy (MAPH) method to fabricate the TC16 (Ti-3Al-5Mo-4.5V) alloy, which overcomes the challenge of low sintering density due to the high percentage of alloying powders (APs) and the presence of Mo element. The relative density of sintered TC16 alloys increases with the Ti-addition in APs, i.e., ∼99.2% and ∼99.4% for sintered TC16 alloys based on pre-hydrogenated 7.5Ti-3Al-5Mo-4.5V (7.5TiMA-Hx) and 12.5Ti-3Al-5Mo-4.5V (12.5TiMA-Hx) powders, respectively. The APs were successfully modified to be brittle and hydrogen-containing, which exhibits similar pressing and sintering characteristics as TiH2 powders. The increased relative density could be ascribed to the brittleness of 7.5/12.5TiMA-Hx, in which particles show sharp corners that can form interlocked structures with TiH2 particles during pressing. Furthermore, the 7.5/12.5TiMA-Hx and TiH2 powder particles release H2 and shrink simultaneously during sintering, which minimizes the difference in volume mismatch between particles and promotes elemental diffusion. The sintered TC16-7.5TiMA-Hx alloy achieves excellent mechanical properties, i.e., an ultimate tensile strength of ∼1004.6 MPa, a yield strength of ∼934.2 MPa and an elongation of ∼15.8%, due to the low porosity and acceptable impurity contents. However, the excessive O and N elements in the sintered TC16-12.5TiMA-Hx alloy can induce premature intergranular fracture, resulting in decreased ductility. Therefore, the innovative MAPH technique is promising in obtaining high density sintered Ti alloys with excellent mechanical properties.

Objective: The main aim of this study was to evaluate the effect of oral probiotics on the human milk microbiota and determine whether that influenced infant microbiota development. Methods: A total of 27 pregnant women were recruited; 14 were assigned to the probiotic group, and the rest were assigned to the control group. Their infants were likewise assigned to the probiotic group or the control group. Pregnant women in the probiotic group received probiotic supplementation from 32 weeks of gestation until delivery. Human milk samples and infant fecal samples were collected at 6 months after delivery, and 16S rRNA sequencing was used to analyze the composition of the human milk and infant gut microbiota (NCT06241222). Results: In the control group, bacterial microbiota were detected in 8 out of 13 milk samples, whereas in the probiotic group, only 6 out of 14 milk samples contained bacterial microbiota. We examined the composition of the human milk and infant gut microbiota in both the control and probiotic groups. Spearman correlation analysis revealed that various genera in human milk were correlated with the infant gut microbiota. The Linear discriminant analysis effect size (LEfSe) showed that 6 bacteria in the human milk microbiota in the control group were significantly more abundant than those in the probiotic group. Nine bacteria were significantly more abundant in the human milk microbiota in the probiotic group than the control group. According to the LEfSe results, 11 bacteria in the infant gut microbiota in the control group were significantly more abundant than those in the probiotic group. Fourteen bacteria were significantly more abundant in the infant gut microbiota in the probiotic group than in the control group. Conclusion: The infant gut microbiota at 6 months has a complicated relationship with the maternal human milk microbiota. Oral probiotic supplementation can change the composition of the human milk microbiota and the infant gut microbiota.

ABSTRACT Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women.IMPORTANCEProbiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.

ABSTRACTFor embryo implantation and fetal development, the maternal immune system undergoes dramatic changes. The mechanisms involved in inducing alterations of maternal immunity have not been fully clarified. Gut microbiome and metabolites were thought to influence the host immune response. During normal pregnancy, notable changes occur in the gut microbiota and metabolites. However, the relationship of these alterations to immune function during pregnancy remains unclear. In this study, we examined gut microbiota, fecal metabolites, plasma metabolites, and cytokines in pregnant women and non-pregnant women. Our findings revealed that, in comparison to non-pregnant women, pregnant women exhibit a significant increase in the relative abundance of Actinobacteriota and notable differences in metabolic pathways related to bile acid secretion. Furthermore, there was a marked reduction in pro-inflammatory cytokines levels in pregnant women. Correlation analyses indicated that these alterations in cytokines may be linked to specific gut bacteria and metabolites. Bacteria within the same microbial modules exhibited consistent effects on cytokines, suggesting that gut bacteria may function as functional groups. Mediation analysis further identified that certain bacteria might influence cytokines through metabolites, such as bile acids and arachidonic acid. Our findings propose potential biological connections between bacteria, metabolites, and immunity, which require further validation in future studies.IMPORTANCEA great number of studies have focused on diseases induced by intestinal microecological disorders and immune imbalances. However, the understanding of how intestinal microbiota interacts with immunity during normal pregnancy, which is fundamental to studying pathological pregnancies related to intestinal microbiota disturbances, has not been well elucidated. Our study employed multi-omics analysis to discover that changes in gut microbiota and metabolites during pregnancy can impact immune function. In addition, we identified several metabolites that may mediate the effect of gut microbes on plasma cytokines. Our study offered new insights into our understanding of the connections between the gut microbiome, metabolome, and the immune system during pregnancy.

Starting microstructure with nonuniform micro-scale grains is designed for the study of microstructure and mechanical properties after rapid heat treatment (RHT) and subsequent aging. RHT was used to retard β grain growth in single-phase β region, while RHT and aging parameters affected size of secondary α and, hence, tensile strength and ductile characteristics. Heating rate for aging is important parameter affecting ω phase precipitation, which, in turn, affects the size of secondary α. Fast heating for aging avoided formation of ω phase, while ω phase formed at slow heating and duplex aging conditions results in refined α precipitations. After single-step aging with fast heating rate, proved by the calculation of strength based on the strengthening mechanism, the RHT temperature for the highest strength is at the bottom of single-phase β region. However, the nonuniformity of starting grain size results in the nonuniform β grain size after RHT, which affects the strengthening and elongation negatively. Proper selection of RHT parameters and fast heating for subsequent aging leads to refined secondary α and high balance of tensile properties (1415 MPa, 5.2%). Formation of ω phase at slow heating and at duplex aging resulted in marked drop in ductility with some variation of strength level (1344 MPa, 2.2%, and 1433 MPa, 0.7% correspondingly). Homogenising of the starting grain size by decreasing the β solution treatment temperature leads to achievement of the best tensile properties (1480 ± 12.5 MPa, 8.2% ± 0.99%).

In recent years, it has become evident that early-life intestinal flora plays a pivotal role in determining human health. Consequently, it is imperative to explore the establishment of neonatal intestinal flora and its influencing factors. Early neonatal intestinal flora is influenced by a multitude of factors, including maternal and infant-related factors, as well as external environment. This review summarizes the colonization mechanism of intestinal flora in the early life of newborns and discussed their influence on the establishment of neonatal intestinal flora, taking into account factors such as delivery mode, gestational age and feeding mode. Additionally, this review delves into the natural or artificial reconstruction of intestinal flora colonization defects in infants born via cesarean section and premature infants, with the goal of establishing a theoretical foundation for preventing and treating issues related to neonatal intestinal flora colonization and associated diseases.

Sintered Ti–6Al–4V compacts prepared from TiH2/60Al40V powder blends were subjected to hot rolling and heat treatment under various conditions. The microstructural evolution and mechanical properties were investigated by X-ray diffraction, scanning electron microscopy, optical microscopy, electron backscatter diffraction, transmission electron microscopy, and universal testing. The hot-rolled Ti–6Al–4V samples with 88% deformation possessed a near-dense lamellar microstructure with ultrafine α lamellae (less than 1 μm). Systematic investigation of the heat treatment temperature and isothermal holding time enabled the evolution of a bimodal microstructure with precipitation of a secondary α phase, ultimately affording an excellent combination of strength and ductility: the yield strength and ultimate tensile strength reached 1248 and 1269 MPa, respectively, with an elongation to fracture of 16.05%.

There is a research gap on the transformation of ofloxacin (OFL) in water supply systems under the action of ClO2. The degradation kinetics of OFL under different ClO2 concentrations, pH and pipe materials, and formation of intermediates, as well as the toxicity of water in water supply systems were first studied. The results showed that the degradation of OFL in PE pipe and deionized water increased with the increase of ClO2 concentration, and the reaction of OFL followed the second-order kinetic model. The removal rate of OFL in deionized water was faster than that in PE pipe. The degradation rate of OFL in PE tube and deionized water were positively correlated with pH. In addition, degradation efficiency of OFL in different pipes followed: cast iron pipe > stainless steel pipe > PE pipe. The detection of OFL intermediates showed that the cleavage of piperazine groups were the main and initial products in the degradation process of OFL. In addition, the decarboxylation intermediates of quinolone groups were also detected. The aquatic toxicity test showed that the degradation of OFL by ClO2 would increase the toxicity of water, therefore, the decrease of OFL may not mean the decrease of water toxicity. HIGHLIGHTS In this study, the degradation of OFL in pilot-scale PE pipe was detected for the first time.; The oxidation rate of OFL was higher in deionized water than in PE pipe; The oxidation of OFL by ClO2 would increase the potential risk of water quality safety.;

PurposeTo investigate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), as an imaging biomarker, for predicting pathological response and prognosis of unresectable hepatocellular carcinoma (HCC) patients treated with Lenvatinib and programmed cell death protein 1 (PD-1) inhibitors as a conversion therapy.MethodsA total of 28 unresectable HCC patients with BCLC stage B or C were treated with Lenvatinib and PD-1 inhibitors before surgery. The 18F-FDG PET/CT scans were acquired before pre- (scan-1) and post-conversion therapy (scan-2). The maximum standardized uptake value (SUVmax), TLR (tumor-to-normal liver standardized uptake value ratio), and the percentages of post-treatment changes in metabolic parameters (ΔSUVmax [%] and ΔTLR [%]) were calculated. Major pathological response (MPR) was identified based on the residual viable tumor in the resected primary tumor specimen (≤10%). Differences in the progression-free survival (PFS) and overall survival (OS) stratified by ΔTLR were examined by the Kaplan-Meier method.Results11 (11/28, 39.3%) patients were considered as MPR responders and 17 (17/28, 60.7%) patients as non-MPR responders after conversion therapy. ΔSUVmax (-70.0 [-78.8, -48.8] vs. -21.7 [-38.8, 5.7], respectively; P

Fabrication of high-performance titanium (Ti) alloys containing high-melting-point elements is challenging via blended elemental powder metallurgy (BEPM), because of the inevitable high porosity induced during pressing and sintering processes. Herein, we propose a novel master-alloy pre-hydrogenation (MAPH) method to fabricate sintered TC16 (Ti-3Al-5Mo-4.5 V) alloy, which possess a nearly full-density (99.2%) and good mechanical properties, i.e., an UTS of ∼ 1004.6 MPa, a YS of ∼934.2 MPa and an EL of ∼15.8%. The pre-hydrogenated 7.5Ti-3Al-5Mo-4.5V-Hx (7.5TiMA-Hx) powder particles show a morphology of sharp corners. Therefore, the 7.5TiMA-Hx and TiH2 particles can get interlocked compactly during compaction and shrink simultaneously during the dehydrogenation process, which minimizes the difference in volume mismatch and ensures the overall uniformity after sintering. Besides, the interlocking compact structure makes the element diffusion easier between the 7.5TiMA-Hx and TiH2 matrix particles, which promotes the healing of porosity. The low porosity can reduce the tendency for propagation of cracks along the grain boundaries of the α layer, leading to a good balance between the strength and ductility of the sintered TC16-7.5TiMA-Hx alloy.

ObjectivesThis study aimed to assess the pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a predictor of the pathological treatment response (PTR) of hepatocellular carcinoma (HCC) patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C.MethodsAll patients (n=20) underwent pretreatment 18F-FDG PET/CT and were treated with conversion therapy and surgery. Patients were categorized into responders (n=9) and non-responders (n=11) according to PTR. The parameters of PET/CT, including lesion size, SUVmean (mean standard uptake value), MTV (metabolic tumor volume), TLG (total lesion glycolysis), SUVpeak (peak standard uptake value), and TLR (tumor-to-normal liver standardized uptake value ratio), were calculated. The diagnostic efficacy was evaluated by receiver operating characteristic analysis (ROC). PTR was compared with pretreatment PET/CT parameters by using Spearman correlation analysis. The patients were followed up.ResultsThere was significant difference in TLR (5.59 ± 1.90 vs. 2.84 ± 1.70, respectively; P=0.003) between responders and non-responders, with the largest area under the curve (sensitivity=100%, specificity=72.7%, AUC=0.899, 95%CI: 0.759-1.000, optimal diagnostic threshold of 3.09). The relationship between 18F-FDG PET/CT parameters and PTR indicated TLR was moderately and positively correlated with pathological treatment response, with correlation coefficients (rs) of 0.69 (P

Background and AimsImmunotherapy with PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) has been proven to be effective against advanced hepatocellular carcinoma (HCC). The aim of this study was to identify the feasibility and safety of subsequent salvage surgery after this combination therapy.Methods and PatientsA retrospective analysis was performed on patients with primary HCC with major vascular invasion between 2018 and 2019. All cases were treated with a combination of a PD-1 inhibitor and TKI agents and subsequent surgery.ResultsA total of 10 HCC cases with major vascular invasion met the successful conversion criteria after the combination therapy, and eight patients underwent subsequent salvage surgery after both radiology and 3D quantitative oncological assessment. Partial response (PR) was recorded in 7 of 10 patients and complete response (CR) in 3 of 10 patients before salvage surgery. Salvage surgery included right hepatectomy, left hepatectomy, and anatomic segmental hepatectomy. The mean intraoperative blood loss was 1,650 ml (50–3,000 ml). No complications beyond Clavien–Dindo level III or postoperative mortality were observed. The viable tumor cell rate of the PR cases (modified response evaluation criteria in solid tumors, mRECIST) varied from 1.5% to 100%, and only one patient had pathology-proven pathological complete response (pCR). The postoperative median follow-up time was 19.7 months (9.1–24.9 months). The 12-month recurrence-free survival rate of all cases who underwent salvage surgery was 75%.ConclusionSalvage surgery was effective and safe after conversion therapy with PD-1 inhibitors plus TKIs and may increase the long-term oncological benefit for patients with unresectable HCC.

The compaction mechanism of titanium hydride powder is an important issue because it has a direct impact on density and strength of green compacts and ultimately on the physical and mechanical properties of a final sintered products. In this paper, the characteristics and compaction behavior of titanium hydride and hydrogenation-dehydrogenation titanium powders are comparatively studied and analyzed for better understanding of compaction mechanism of brittle low-strength titanium hydride. The results indicate that the particles of titanium hydride powder are easily crushed under compaction loading at relatively low pressure well below compression strength of bulk titanium hydride, the degree of particle crushed increases with the increase of pressure. The compaction behavior of titanium hydride powder mainly includes the rearrangement and crushing of particles in the early compaction stage, minor plastic deformation, if any, and further rearrangement of particle fragments with filling the pores in the later stage. Such compaction behavior provides relative density of green hydride compacts higher than that for titanium powder of the same size. The relatively coarse titanium hydride powder with wide particle size distribution is easier to fill the pores providing highest green density.

Virus–host interactions are critical for virus replication, virulence, and pathogenicity. The Bombyx mori nucleopolyhedrovirus (BmNPV) is a typical model baculovirus, representing one of the most common and harmful pathogens in sericulture. Herein, we used co-immunoprecipitation to identify candidate proteins with potential interactions with BmNPV. First, a recombinant BV virus particle rBmBV-egfp-p64-3×flag-gp64sp was constructed using a MultiBac baculovirus multigene expression system. Co-immunoprecipitation experiments were then performed with the recombinant BV virus infected with BmN cells and Dazao silkworms. LC-MS/MS analysis revealed a total of 845 and 1368 candidate proteins were obtained from BmN cells and silkworm samples, respectively. Bioinformatics analysis (Gene Ontology, KEGG Pathway) was conducted for selection of proteins with significant enrichment for further confirmation of the effects on BmNPV replication. Overall, the results showed that SEC61 and PIC promoted the replication of BmNPV, while FABP1 inhibited the replication of BmNPV. In summary, this study reveals the potential proteins involved in BmNPV invasion and proliferation in the host and provides a platform for identifying the potential receptor proteins of BmNPV.

Ti80 (Ti-6Al-3Nb-2Zr-1Mo) is a recently developed near-α titanium alloy that is generally applied in marine applications. In this study, the feasibility of producing the Ti80 alloy via the blended elemental powder metallurgy (BEPM) press-and-sinter method was demonstrated. Generally, the presence of elements with low diffusion mobility in titanium (Mo, Nb) creates difficulties with diffusion-controlled healing of the porosity and the realization of microstructural uniformity. These issues were minimized by using titanium hydride powder instead of titanium powder to activate the sintering, as well as by the proper selection of complex alloying powders rather than elemental powders to promote alloy uniformity. The sintering time-temperature conditions to obtain a chemically and microstructurally homogeneous and nearly-dense alloy microstructure were determined. Special attention was given to the microstructural peculiarities of the sintered material to regulate its mechanical characteristics. Finally, the processing parameters were determined to reach the properties required by alloy specifications. This enabled both the fully beta transformed lamellar microstructure inherent to beta phase field sintering and one that could be modified via post sintering thermomechanical processing.

To study the effects of paeoniflorin on the behavioral manifestations, levels of neurotransmitters in the hippocampus, and axial response in an anxiety model of acute myocardial infarction. 21 rats were randomly divided into 3 groups; control group, acute myocardial infarction+anxiety group, and acute myocardial infarction+anxiety+paeoniflorin group, with 7 rats in each group. An acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in rats, and mild stress was used to induce anxiety in rats. In the open field test, compared with the horizontal and vertical exercise of the control group, the acute myocardial infarction+anxiety group decreased, and the acute myocardial infarction+anxiety+paeoniflorin group increased compared with the horizontal and vertical exercise of acute myocardial infarction+anxiety group. In the elevated test, compared with the control group, the time of staying at the open arm and entering the open arm was decreased in the acute myocardial infarction+anxiety group, and increased in the acute myocardial infarction+anxiety+paeoniflorin group compared with the acute myocardial infarction+anxiety group. Compared with the control group, chemokine receptor type 4, interleukin-1 beta, interleukin-18 and norepinephrine increased and C-X-C motif chemokine ligand 12 decreased in acute myocardial infarction+anxiety group. Compared with acute myocardial infarction+anxiety group, chemokine receptor type 4, interleukin-1 beta, interleukin-18 and norepinephrine increased and C-X-C motif chemokine ligand 12 decreased in acute myocardial infarction+anxiety+paeoniflorin group. Compared with the control group, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in acute myocardial infarction+anxiety group were higher than those in control group, acute myocardial infarction+anxiety+paeoniflorin 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in acute myocardial infarction+anxiety group were significantly higher than those in acute myocardial infarction+anxiety group, C-X-C motif chemokine ligand 12 and chemokine receptor type 4 protein expression in acute myocardial infarction+anxiety group was higher than that in control group, while acute myocardial infarction+anxiety+paeoniflorin C-X-C motif chemokine ligand 12 and chemokine receptor type 4 protein expression was lower than that in acute myocardial infarction+anxiety group. Paeoniflorin has anti-anxiety effect, can restore the balance of neurotransmitters in hippocampus, and can improve the inflammatory response of acute myocardial infarction with anxiety model. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), as an imaging biomarker, for predicting pathological response and prognosis of unresectable hepatocellular carcinoma (HCC) patients treated with Lenvatinib and programmed cell death protein 1 (PD-1) inhibitors as a conversion therapy. Methods: A total of 28 unresectable HCC patients with BCLC stage B or C were treated with Lenvatinib and PD-1 inhibitors before surgery. The 18F-FDG PET/CT scans were acquired before pre- (scan-1) and post-conversion therapy (scan-2). The maximum standardized uptake value (SUVmax), TLR (tumor-to-normal liver standardized uptake value ratio), and the percentages of post-treatment changes in metabolic parameters (DSUVmax [%] and DTLR [%]) were calculated. Major pathological response (MPR) was identified based on the residual viable tumor in the resected primary tumor specimen (=10%). Differences in the progressionfree survival (PFS) and overall survival (OS) stratified by DTLR were examined by the Kaplan-Meier method. Results: 11 (11/28, 39.3%) patients were considered as MPR responders and 17 (17/28, 60.7%) patients as non-MPR responders after conversion therapy. DSUVmax (-70.0 [-78.8, -48.8] vs. -21.7 [-38.8, 5.7], respectively; P<0.001) and DTLR (-67.6 [-78.1, -56.8] vs. -18.6 [-27.9, 4.0], respectively; P<0.001) were reduced in the responder group than those in the non-responder group. According to the results of the receiver operating characteristic curve analysis, DTLR showed an excellent predictive value for the MPR of primary HCC lesions (area under curve=0.989, with the optimal diagnostic threshold of -46.15). When using DTLR of -21.36% as a threshold, patients with DTLR-based metabolic response had superior PFS (log-rank test, P=0.001) and OS (log-rank test, P=0.016) compared with those without DTLR-based metabolic response. Conclusion: 18F-FDG PET is a valuable tool for predicting pathological response and prognosis of unresectable HCC patients treated by Lenvatinib combined with PD-1 as a conversion therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The Global Campaign Against Epilepsy demonstration project in rural China aimed: to reduce the treatment gap and morbidity of people with epilepsy by using community-level interventions; to train and educate health professionals; to dispel stigma; to identify potential for prevention and to develop models of integration of epilepsy control into the local health systems. We report the overall results of the demonstration project, focusing on the prevalence and the change in the treatment gap of epilepsy after an intervention. METHODS: Door-to-door epidemiological surveys were carried out before, and 6 months after the end of, an intervention project for epilepsy in rural settings in five provinces of China. The intervention consisted of a treatment programme available to patients without prior appropriate treatment and a public health educational programme about epilepsy. The sampled population in the second survey was 51 644 people. FINDINGS: In the second survey, epilepsy was confirmed in 320 people, yielding a lifetime prevalence of 6.2/1000 and a prevalence of active epilepsy of 4.5/1000. The lifetime prevalence and prevalence of active epilepsy in the first survey were 7.0/1000 and 4.6/1000, respectively. The treatment gap of active epilepsy in the second survey was 49.8%, 12.8 percentage points lower than that of the first survey (62.6%). CONCLUSION: The results of this study suggest that the intervention measures used were possibly effective and evidently feasible in rural China, contributing to a decrease in the treatment gap of epilepsy.

Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, β-galactosidase (β-gal). Growth of β-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with β-gal and FasL DNA compared with those vaccinated with β-gal or FasL DNA. We did not detect increased numbers of β-gal-specific CD8+ T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone. Subtype analysis of anti-β-gal antibody produced by the combination of β-gal and FasL DNA or β-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with β-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than β-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

We report on the use of PDMS multichannels for affinity studies of DNA aptamer–human Immunoglobulin E (IgE) interactions by surface plasmon resonance imaging (SPRi). The sensing surface was prepared with thiol-terminated aptamers through a self-assembling process in the PDMS channels defined on a gold substrate. Cysteamine was codeposited with the thiol aptamers to promote proper spatial arrangement of the aptamers and thus maintain their optimal binding efficiencies. Four aptamers with different nucleic acid sequences were studied to test their interaction affinity toward IgE, and the results confirmed that aptamer I (5′-SH-GGG GCA CGT TTA TCC GTC CCT CCT AGT GGC GTG CCC C-3′) has the strongest binding affinity. Control experiments were conducted with a PEG-functionalized surface and IgG was used to replace IgE in order to verify the selective binding of aptamer I to the IgE molecules. A linear concentration-dependent relationship between IgE and aptamer I was obtained, and a 2-nM detection limit was achieved. SPRi data were further analyzed by global fitting, and the dissociation constant of aptamer I–IgE complex was found to be 2.7 × 10−7 M, which agrees relatively well with the values reported in the literature. Aptamer affinity screening by SPR imaging demonstrates marked advantages over competing methods because it does not require labeling, can be used in real-time, and is potentially high-throughput. The ability to provide both qualitative and quantitative results on a multichannel chip further establishes SPRi as a powerful tool for the study of biological interactions in a multiplexed format. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Current strategies for cancer gene therapy consist mainly of direct inhibition of tumor cell growth and activation of systemic host defense mechanisms. Conventional chemotherapy and radiotherapy, even considered to be temporally suppressing tumor growth, suppress immune responses; therefore, we examined potential clinical feasibility of virus-mediated tumor destruction, which can rather enhance immunity. We showed that human tumors were more susceptible to adenoviruses (Ad) in which the E1A expression was controlled by a putative tumor promoter than normal cells, and that a replication of the Ad was greater in tumor cells than in normal cells. We also demonstrated that the intratumoral injection of the Ad bearing a tumor promoter inhibited the subsequent tumor growth in vivo. The E1A expression was detected in the tumors injected with the Ad but not in non-tumorous tissues of the same mice. The Ad modified to show the regulated E1A expression is thereby oncolytic in nature. Antitumor immune responses are initiated after the acquisition of putative tumor antigen(s) by dendritic cells (DCs); therefore, enhanced antigen presentation is a crucial step for the early phase of cell-mediated immunity. Destruction of tumors can release the tumor antigens and DCs come to recognize them thereafter. We found that the stimulation of Fas expressed on DCs with Fas ligand (FasL) did not induce apoptosis of DCs but rather enhanced the antigen presentation. Activation of DCs induced production of a number of cytokines, and we showed that the interleukin-12 family secreted from tumors could induce systemic antitumor immunity. We presume that the administration of oncolytic Ad, which can destroy local tumors and subsequently make the putative tumor antigen(s) released from the tumors, stimulation of DCs with the Fas/FasL signal pathway and secretion of DCs-derived cytokines coordinately produce synergistic antitumor effects and that a combinatory application of these procedures can be a possible therapeutic strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Thrombocytopenia Should not be Barrier for Lymph-node Biopsy" published in the previous issue is presented.

Fas ligand (FasL) is a member of the TNF ligand superfamily and induces apoptotic cell death through Fas-mediated pathways. Our previous studies demonstrated that transduction of FasL in tumors produced anti-tumor effects, when they were inoculated into mice and that expressed FasL on tumor cells enhanced antigen acquisition of Fas-positive dendritic cells to elicit tumor-specific immune responses. We here examined the effectiveness of DNA vaccine, which included FasL as an adjuvant and β-galastosidase (β-gal) as an antigen, by measuring the β-gal-specific immune responses. The pcDNA3-based β-gal-expressing vector (β-gal DNA), the pCAGGS- based FasL-expressing vector (FasL DNA) or both vectors (β- gal+FasL DNA) were administrated into quadriceps of DBA/2 mice and subsequently the mice were inoculated with the β-gal-expressing P815 (P815 β) cells. The growth of P815β tumors was retarded in the mice immunized with β-gal+FasL DNA but not β-gal DNA or FasL DNA alone. The mice administrated with the β-gal+FasL DNA produced greater amounts of anti- β-gal antibody than those injected with β-gal DNA alone. In particular, production of IgG2a subclass of anti- β-gal antibody was increased in the mice immunized with β- gal+FasL DNA, when compared with mice administered with β-gal DNA alone. These results revealed that administration of DNA encoding the FasL gene combined with DNA of the β-gal gene could successfully immunized mice and enhanced humoral immunity against β-gal protein; consequently, growth of β-gal-expressing tumors was retarded. Administration of DNA encoding the FasL gene can be an adjuvant and injection together with DNA of an antigenic protein could be applicable as a method of DNA vaccination.Molecular Therapy (2006) 13, S108–S108; doi: 10.1016/j.ymthe.2006.08.337 [ABSTRACT FROM AUTHOR]

Background: To compare glomerular filtration rate (GFR) among individuals, GFR is usually scaled to body surface area (BSA) based on the ratio method, which has been debated for its accuracy in recent years. Reference to the BSA as a normalization standard is the most common method currently in use but has limitations. This study was designed to a better variable to scale GFR., Methods: We measured 99mTc- diethylene triamine pentaacetic acid plasma clearance (uncorrected GFR, uGFR) for 322 healthy adults who were enrolled according to the SENIEUR protocol. The individuals were randomly grouped into A and B for regressing and validating the optimal variable, respectively. Nonlinear regression was performed against uGFR, and the selected independent variables were body weight, height, age, and sex., Results: Among several tested models, the regression coefficients of weight-age formula (W-A) were in narrower 95% confidence interval (CI). The coefficient of determination of the regression line between W-A and uGFR, as an indicator to explain the percentage of variations of GFR, was higher than that of other variables in both groups. The coefficient of determination of the regression line between W-A and uGFR was 0.571, which was higher than that of BSA (0.203) or TBW (0.241)., Conclusion: The index variable, based on both body weight and age, has a better statistical relationship to uGFR and is a better variable to scale GFR in adults.