Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective

Liver cancer is the fourth most prevalent and the second most lethal cancer in China. Hepatitis B virus (HBV) infection represents a major risk factor for hepatocellular carcinoma (HCC). Liver ultrasonography plus alpha-fetoprotein every 6 months continues to be the predominant surveillance modality. The age-Male-ALBI-Platelets score was recommended in the recent 2022 Chinese guidelines to predict HCC occurrence. The Chinese liver cancer (CNLC) staging system proposed in the 2017 guidelines continues to be the standard model for staging with modifications in the treatment allocations. Considering the aggressive nature of HBV-associated HCC, multimodal and high-intensity strategies like the addition of immunotherapy-based systemic treatment to local therapies, including resection, ablation, and intra-arterial therapies, have been adopted in real-life practices in China. The latest Chinese guidelines recommend atezolizumab plus bevacizumab, suntilimab plus a bevacizumab analog, lenvatinib, sorafenib, donafenib, and FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy as first-line treatment without priority. Regorafenib, apatinib, camrelizumab, and tislelizumab have been added as second-line systemic therapies for patients who progressed on sorafenib. Systemic therapies adopted in real-life practice are sophisticated with various combination modalities and different sequences

Eye movement characteristics in a mental rotation task presented in virtual reality

IntroductionEye-tracking technology provides a reliable and cost-effective approach to characterize mental representation according to specific patterns. Mental rotation tasks, referring to the mental representation and transformation of visual information, have been widely used to examine visuospatial ability. In these tasks, participants visually perceive three-dimensional (3D) objects and mentally rotate them until they identify whether the paired objects are identical or mirrored. In most studies, 3D objects are presented using two-dimensional (2D) images on a computer screen. Currently, visual neuroscience tends to investigate visual behavior responding to naturalistic stimuli rather than image stimuli. Virtual reality (VR) is an emerging technology used to provide naturalistic stimuli, allowing the investigation of behavioral features in an immersive environment similar to the real world. However, mental rotation tasks using 3D objects in immersive VR have been rarely reported.MethodsHere, we designed a VR mental rotation task using 3D stimuli presented in a head-mounted display (HMD). An eye tracker incorporated into the HMD was used to examine eye movement characteristics during the task synchronically. The stimuli were virtual paired objects oriented at specific angular disparities (0, 60, 120, and 180°). We recruited thirty-three participants who were required to determine whether the paired 3D objects were identical or mirrored.ResultsBehavioral results demonstrated that the response times when comparing mirrored objects were longer than identical objects. Eye-movement results showed that the percent fixation time, the number of within-object fixations, and the number of saccades for the mirrored objects were significantly lower than that for the identical objects, providing further explanations for the behavioral results.DiscussionIn the present work, we examined behavioral and eye movement characteristics during a VR mental rotation task using 3D stimuli. Significant differences were observed in response times and eye movement metrics between identical and mirrored objects. The eye movement data provided further explanation for the behavioral results in the VR mental rotation task

Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study

BACKGROUND: Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH) cDNA library methodology and Affymetrix GeneChip(® )technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC), and evaluated the potential for novel gene discovery using the SSH methodology. RESULTS: The same RNA samples isolated from peripheral blood monocyte precursors and immature DC (iDC) were used for GeneChip microarray probing and SSH cDNA library construction. 10,000 clones from each of the two-way SSH libraries (iDC-monocytes and monocytes-iDC) were picked for sequencing. About 2000 transcripts were identified for each library from 8000 successful sequences. Only 70% to 75% of these transcripts were represented on the U95 series GeneChip microarrays, implying that 25% to 30% of these transcripts might not have been identified in a study based only on GeneChip microarrays. In addition, about 10% of these transcripts appeared to be "novel", although these have not yet been closely examined. Among the transcripts that are also represented on the chips, about a third were concordantly discovered as differentially regulated between iDC and monocytes by GeneChip microarray transcript profiling. The remaining two thirds were either not inferred as differentially regulated from GeneChip microarray data, or were called differentially regulated but in the opposite direction. This underscores the importance both of generating reciprocal pairs of SSH libraries, and of real-time RT-PCR confirmation of the results. CONCLUSIONS: This study suggests that SSH could be used as an alternative and complementary transcript profiling tool to GeneChip microarrays, especially in identifying novel genes and transcripts of low abundance

Hypoxic acclimatization training improves the resistance to motion sickness

ObjectiveVestibular provocation is one of the main causes of flight illusions, and its occurrence is closely related to the susceptibility of motion sickness (MS). However, existing training programs have limited effect in improving the resistance to motion sickness. In this study, we investigated the effects of hypoxia acclimatization training (HAT) on the resistance to motion sickness.MethodsHealthy military college students were identified as subjects according to the criteria. MS model was induced by a rotary chair. Experimental groups included control, HAT, 3D roller training (3DRT), and combined training.ResultsThe Graybiel scores were decreased in the HAT group and the 3DRT group and further decreased in the combined training group in MS induced by the rotary chair. Participants had a significant increase in blood pressure after the rotary chair test and a significant increase in the heart rate during the rotary chair test, but these changes disappeared in all three training groups. Additionally, LFn was increased, HFn was decreased, and LF/HF was increased accordingly during the rotary chair test in the control group, but the changes of these three parameters were completely opposite in the three training groups during the rotary chair test. Compared with the control group, the decreasing changes in pupillary contraction velocity (PCV) and pupillary minimum diameter (PMD) of the three training groups were smaller. In particular, the binocular PCV changes were further attenuated in the combined training group.ConclusionOur research provides a possible candidate solution for training military pilots in the resistance to motion sickness

Experimental evidence to understand mechanical causes of retinal detachment following blunt trauma.

PURPOSE: This study aimed to perform an in vitro experiment to simulate retinal detachment caused by blunt impact, and provide experimental evidence to understand mechanical causes of traumatic retinal detachment. METHODS: The experiment was conducted on twenty-two fresh porcine eyes using a bespoke pendulum testing device at two energy levels (0.1J for low energy and 1.0J for high energy). We examined dynamic forces and mechanical responses to the impact, including global deformations, intraocular pressure changes and the energy absorption. Another set of twenty-two eyes underwent pathological examination immediately after being subjected to blunt impact. Twelve additional intact eyes were examined as controls. All pathological sections were scored to indicate whether retinal detachment had occurred. RESULTS: A dynamic variation in intraocular pressure was detected following impact and exhibited an approximate sinusoidal oscillation-attenuation profile. The peaks of impact force were 12.9 ± 1.9 N at low-energy level and 34.8 ± 9.8 N at high-energy level, showing a significant difference (p < 0.001). The positive and negative peaks of intraocular pressure were 149.4 ± 18.9 kPa and -10.9 ± 7.2 kPa at low-energy level, and 274.5 ± 55.2 kPa and -35.7 ± 23.7 kPa at high-energy level, showing significant differences (p < 0.001 for both levels). Retinal detachments were observed in damaged eyes while few detachments were found in control eyes. The occurrence rate of retinal detachment differed significantly (p < 0.05) between the high- and low-energy impact groups. CONCLUSIONS: This study provided experimental evidence that shockwaves produced by blunt trauma break the force equilibrium and lead to the oscillation and negative pressure, which mainly contribute to traumatic retinal detachment

Evaluation of the prognostic value of paraoxonase 1 in the recurrence and metastasis of hepatocellular carcinoma and establishment of a liver-specific predictive model of survival

Abstract Background Hepatocellular carcinoma is a malignant tumor with a highly invasive and metastatic phenotype, and the detection of potential indicators associated with its recurrence and metastasis after surgical resection is critical for patient survival. Methods Transcriptome data for large cohorts (n = 1432) from multicenter sources were comprehensively analyzed to explore such potential signatures. The prognostic value of the selected indicators was investigated and discussed, and a comparison with conventional clinicopathological features was performed. A survival predictive nomogram for 5-year survival was established with the selected indicator using the Cox proportional hazards regression. To validate the indicator at the protein level, we performed immunohistochemical staining with paraffin-embedded slides of hepatocellular carcinoma samples (n = 67 patients) from our hospital. Finally, a gene set enrichment analysis (GSEA) was performed to detect the underlying biological processes and internal mechanisms. Results The liver-specific protein paraoxonase 1 (PON1) was found to be the most relevant indicator of tumor recurrence, invasiveness, and metastasis in the present study, and the downregulation of PON1 might reveal poor survival for patients with hepatocellular carcinoma. The C-index of the PON1-related nomogram was 0.714, thus indicating a more effective predictive performance than the 7th American Joint Committee on Cancer (AJCC) tumor stage (0.534), AJCC T stage (0.565), or alpha-fetoprotein (0.488). The GSEA revealed that PON1 was associated with several hepatocellular carcinoma-related pathways, including the cell cycle, DNA replication, gap junction and p53 downstream pathways. Conclusions The downregulation of paraoxonase 1 may suggest worse outcomes and a higher recurrence rate. Thus, paraoxonase 1 might represent an indicator for predicting the survival of patients with hepatocellular carcinoma

Age-related differences in upper limb motor performance and intrinsic motivation during a virtual reality task

Abstract Background In recent years, virtual reality (VR) has evolved from an alternative to a necessity in older adults for health, medical care, and social interaction. Upper limb (UL) motor skill, is an important ability in manipulating VR systems and represents the brain’s regulation of movements using the UL muscles. In this study, we used a haptic-feedback Virtual Box and Block Test (VBBT) system and an Intrinsic Motivation Inventory (IMI) to examine age-related differences in UL motor performance and intrinsic motivation in VR use. The findings will be helpful for the development of VR applications for older adults. Methods In total, 48 young and 47 older volunteers participated in our study. The parameters including VBBT score, number of velocity peaks, velocity, grasping force and trajectory length were calculated to represent the task performance, manual dexterity, coordination, perceptive ability and cognitive ability in this study. Results Age-related differences could be found in all the parameters (all p <  0.05) in VR use. Regression analysis revealed that the task performance of young adults was predicted by the velocity and trajectory length (R2 = 64.0%), while that of older adults was predicted by the number of velocity peaks (R2 = 65.6%). Additionally, the scores of understandability, relaxation and tiredness were significantly different between the two groups (all p <  0.05). In older adults, the understandability score showed large correlation with the IMI score (|r| = 0.576, p <  0.001). In young adults, the correlation was medium (|r| = 0.342, p = 0.017). No significant correlation was found between the IMI score and VBBT score (|r| = 0.142, p = 0.342) in older adults, while a medium correlation (|r| = 0.342, p = 0.017) was found in young adults. Conclusions The findings demonstrated that decreased smoothness in motor skills dominated the poor VR manipulation in older adults. The experience of understandability is important for older adults’ intrinsic motivation in VR use

Association of diet and lifestyle factors with semen quality in male partners of Chinese couples preparing for pregnancy

Abstract Background Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality. Methods A total of 466 males from the Guangzhou Women and Children’s Medical Center’s pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality. Results Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.610 6 vs. 63.7106 vs. 66.1*106; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.810 6 vs. 224.6106; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03–0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00–0.30; P = 0.012), and count (OR: 0.12, CI 0.03–0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06–0.51; P = 0.001 and OR: 0.11, CI 0.03–0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24–0.95; P = 0.034). Conclusions Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality

Target the Enhancement of DIET-Based CO₂‑Dependent Methanogenesis via Synergy of Magnetite Addition and Inorganic Carbon Recirculation

In anaerobic systems, CO2-dependent methanogens as terminal electron acceptors determine the feasibility of organic degradation. In this study, targeting the enhancement of CO2-dependent methanogenesis, a strategy coupling the addition of magnetite and inorganic carbon recirculation was proposed. The results showed that the strategy facilitated the enrichment of Methanosaeta and Methanosarcina to the greatest extent (abundance of 42.9 and 38.8%, respectively), and metaproteomic analysis revealed that their enzymes coding for CO2-dependent methanogenesis were maximally expressed, compared with the single strategy. Combined with electrochemical analysis, magnetite was speculated to trigger direct interspecies electron transfer (DIET)-based syntrophy with extracellular redox-active mediators (Cyt C and flavins) in anaerobic sludge. The ability of Methanosaeta and Methanosarcina to accept electrons was significantly improved, as evidenced by the upregulated electron transfer proteins, such as F420H2 dehydrogenase, coenzyme F420 hydrogenase, and CoB-CoM heterodisulfide reductase. Meanwhile, Methanosaeta and Methanosarcina enhanced HCO3– takeup into cells via an ABC-type transport system under the condition of inorganic carbon recirculation, thus thermodynamically inducing electron consumption and inorganic carbon reduction. In summary, the coupling strategy had a great synergistic effect on the enhancement of DIET-based CO2-dependent methanogenesis and endowed the up-flow anaerobic sludge bed reactor with superior methanogenic performance for stable anaerobic wastewater treatment

Interhemispheric multisensory perception and Bayesian causal inference

Summary: In daily life, our brain needs to eliminate irrelevant signals and integrate relevant signals to facilitate natural interactions with the surrounding. Previous study focused on paradigms without effect of dominant laterality and found that human observers process multisensory signals consistent with Bayesian causal inference (BCI). However, most human activities are of bilateral interaction involved in processing of interhemispheric sensory signals. It remains unclear whether the BCI framework also fits to such activities. Here, we presented a bilateral hand-matching task to understand the causal structure of interhemispheric sensory signals. In this task, participants were asked to match ipsilateral visual or proprioceptive cues with the contralateral hand. Our results suggest that interhemispheric causal inference is most derived from the BCI framework. The interhemispheric perceptual bias may vary strategy models to estimate the contralateral multisensory signals. The findings help to understand how the brain processes the uncertainty information coming from interhemispheric sensory signals