Re-inventing a better wheel? Serplulimab for squamous cell lung cancer.

Immune checkpoint inhibitors have reshaped the treatment landscape of non-small cell lung cancer (NSCLC). However, chemoimmunotherapy trials dedicated to squamous NSCLC are limited. In this issue of Cancer Cell, Zhou et al. demonstrate serplulimab plus chemotherapy as an effective first-line regimen to treat patients with advanced squamous NSCLC.

Effects of Early Short-Course Corticosteroids on Immune-Related Adverse Events in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. METHODS: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. RESULTS: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35-1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12-0.85; p = 0.013). CONCLUSION: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs.

Working Memory Training for Children Using the Adaptive, Self-Select, and Stepwise Approaches to Setting the Difficulty Level of Training Activities: Protocol for a Randomized Controlled Trial.

BACKGROUND: A common yet untested assumption of cognitive training in children is that activities should be adaptive, with difficulty adjusted to the individual's performance in order to maximize improvements on untrained tasks (known as transfer). Working memory training provides the ideal testbed to systematically examine this assumption as it is one of the most widely studied domains in the cognitive training literature, and is critical for children's learning, including following instructions and reasoning. OBJECTIVE: This trial aimed to examine children's outcomes of working memory training using adaptive, self-select (child selects difficulty level), and stepwise (difficulty level increases incrementally) approaches to setting the difficulty of training activities compared to an active control condition immediately and 6-month postintervention. While the aim is exploratory, we hypothesized that children allocated to a working memory training condition would show greater improvements: (1) on near transfer measures compared to intermediate and far transfer measures and (2) immediately postintervention compared to 6-month postintervention. METHODS: This double-blinded, active-controlled, parallel-group randomized trial aimed to recruit 128 children aged 7 to 11 years from 1 metropolitan primary school in Melbourne, Australia. Following baseline testing, children were randomized into 1 of 4 conditions: adaptive, self-select, or stepwise working memory training, or active control. An experimental intervention embedded in Minecraft was developed for teachers to deliver in class over 2 consecutive weeks (10 × 20-minute sessions). The working memory training comprised 2 training activities with processing demands similar to daily activities: backward span and following instructions. The control comprised creative activities. Pre- and postintervention, children completed a set of working memory tests (near and intermediate transfer) and the Raven's Standard Progressive Matrices (far transfer) to determine training outcomes, as well as motivation questionnaires to determine if motivations toward learning and the intervention were similar across conditions. Caregivers completed the ADHD-Rating Scale-5 to measure their child's attention (far transfer). Statistical analysis will include traditional null hypothesis significance testing and Bayesian methods to quantify evidence for both the null and alternative hypotheses. RESULTS: Data collection concluded in December 2022. Data are currently being processed and analyzed. CONCLUSIONS: This trial will determine whether the adaptive approach to setting the difficulty of training activities maximizes cognitive training outcomes for children. This trial has several strengths: it adopts best practices for cognitive training studies (design, methods, and analysis plan); uses a range of measures to detect discrete levels of transfer; has a 6-month postintervention assessment; is appropriately powered; and uses an experimental working memory training intervention based on our current understanding of the cognitive mechanisms of training. Findings will inform future research and design of cognitive training interventions and highlight the value of the evidence-based principles of cognitive training. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12621000990820; https://www.anzctr.org.au/ACTRN12621000990820.aspx. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47496.

Multi-level Force-dependent Allosteric Enhancement of αE-catenin Binding to F-actin by Vinculin.

Classical cadherins are transmembrane proteins whose extracellular domains link neighboring cells, and whose intracellular domains connect to the actin cytoskeleton via ß-catenin and α-catenin. The cadherin-catenin complex transmits forces that drive tissue morphogenesis and wound healing. In addition, tension-dependent changes in αE-catenin conformation enables it to recruit the actin-binding protein vinculin to cell-cell junctions, which contributes to junctional strengthening. How and whether multiple cadherin-complexes cooperate to reinforce cell-cell junctions in response to load remains poorly understood. Here, we used single-molecule optical trap measurements to examine how multiple cadherin-catenin complexes interact with F-actin under load, and how this interaction is influenced by the presence of vinculin. We show that force oriented toward the (-) end of the actin filament results in mean lifetimes 3-fold longer than when force was applied towards the barbed (+) end. We also measured force-dependent actin binding by a quaternary complex comprising the cadherin-catenin complex and the vinculin head region, which cannot itself bind actin. Binding lifetimes of this quaternary complex increased as additional complexes bound F-actin, but only when load was oriented toward the (-) end. In contrast, the cadherin-catenin complex alone did not show this form of cooperativity. These findings reveal multi-level, force-dependent regulation that enhances the strength of the association of multiple cadherin/catenin complexes with F-actin, conferring positive feedback that may strengthen the junction and polarize F-actin to facilitate the emergence of higher-order cytoskeletal organization.

Crystallization Kinetics in an Immiscible Polyolefin Blend.

Motivated by the problem of brittle mechanical behavior in recycled blends of high density polyethylene (HDPE) and isotactic polypropylene (iPP), we employ optical microscopy, rheo-Raman, and differential scanning calorimetry (DSC) to measure the composition dependence of their crystallization kinetics. Raman spectra are analyzed via multivariate curve resolution with alternating least-squares (MCR-ALS) to provide component crystallization values. We find that iPP crystallization behavior varies strongly with blend composition. Optical microscopy shows that three crystallization kinetic regimes correspond to three underlying two-phase morphologies: HDPE droplets in iPP, the inverse, and cocontinuous structures. In the HDPE droplet regime, iPP crystallization temperature decreases sharply with increasing HDPE composition. For cocontinuous morphologies, iPP crystallization is delayed, but the onset temperature changes little with the exact blend composition. In the iPP droplet regime, the two components crystallize nearly concurrently. Rheological measurements are consistent with these observations. DSC indicates that the enthalpy of crystallization of the blends is less than the weighted values of the individual components, providing a possible clue for the decreased iPP crystallization temperatures.

Toward a flow-dependent phase-stability criterion: Osmotic pressure in sticky flowing suspensions.

Equilibrium phase instability of colloids is robustly predicted by the Vliegenthart-Lekkerkerker (VL) critical value of the second virial efficient, but no such general criterion has been established for suspensions undergoing flow. A transition from positive to negative osmotic pressure is one mechanical hallmark of a change in phase stability in suspensions and provides a natural extension of the equilibrium osmotic pressure encoded in the second virial coefficient. Here, we propose to study the non-Newtonian rheology of an attractive colloidal suspension using the active microrheology framework as a model for focusing on the pair trajectories that underlie flow stability. We formulate and solve a Smoluchowski relation to understand the interplay between attractions, hydrodynamics, Brownian motion, and flow on particle microstructure in a semi-dilute suspension and utilize the results to study the viscosity and particle-phase osmotic pressure. We find that an interplay between attractions and hydrodynamics leads to dramatic changes in the nonequilibrium microstructure, which produces a two-stage flow-thinning of viscosity and leads to pronounced flow-induced negative osmotic pressure. We summarize these findings with an osmotic pressure heat map that predicts where hydrodynamic enhancement of attractive bonds encourages flow-induced aggregation or phase separation. We identify a critical isobar-a flow-induced critical pressure consistent with phase instability and a nonequilibrium extension of the VL criterion.

Modeling of the Long-Term Epidemic Dynamics of COVID-19 in the United States.

Coronavirus 2019 (COVID-19) is causing a severe pandemic that has resulted in millions of confirmed cases and deaths around the world. In the absence of effective drugs for treatment, non-pharmaceutical interventions are the most effective approaches to control the disease. Although some countries have the pandemic under control, all countries around the world, including the United States (US), are still in the process of controlling COVID-19, which calls for an effective epidemic model to describe the transmission dynamics of COVID-19. Meeting this need, we have extensively investigated the transmission dynamics of COVID-19 from 22 January 2020 to 14 February 2021 for the 50 states of the United States, which revealed the general principles underlying the spread of the virus in terms of intervention measures and demographic properties. We further proposed a time-dependent epidemic model, named T-SIR, to model the long-term transmission dynamics of COVID-19 in the US. It was shown in this paper that our T-SIR model could effectively model the epidemic dynamics of COVID-19 for all 50 states, which provided insights into the transmission dynamics of COVID-19 in the US. The present study will be valuable to help understand the epidemic dynamics of COVID-19 and thus help governments determine and implement effective intervention measures or vaccine prioritization to control the pandemic.

Sticky-probe active microrheology: Part 2. The influence of attractions on non-Newtonian flow.

We derive a theoretical framework for the non-Newtonian viscosity of a sticky, attractive colloidal dispersion via active microrheology by modeling detailed microscopic attractive and Brownian forces between particles. Actively forcing a probe distorts the surrounding arrangement of particles from equilibrium; the degree of this distortion is characterized by the Péclet number, Pe≡Fext/(2kT/a), where kT is the thermal energy and a the probe size. Similarly, the strength of attractive interactions relative to Brownian motion is captured by the second virial coefficient, B2. We formulate a Smoluchowski equation governing the pair configuration as it evolves with external and attractive forces. The microviscosity is then computed via non-equilibrium statistical mechanics. For active probe forcing, the familiar hard-sphere boundary-layer and wake structures emerge as Pe grows strong, but attractions alter its shape: changes in relative probe motion arising from its attraction to the bath particles can lead to a high-Pe, strong-attraction flipping of the microstructure, where an upstream depletion boundary layer forms, along with a downstream accumulation wake. This highly distorted structure is analyzed at the micro-mechanical level, where changes in the time spent upstream or downstream from a bath particle lead to hypo- and hyper-viscosity. When attractions are strong, separating the interparticle microviscosity into contributions from attractions and repulsions reveals an attractive undershoot and a repulsive overshoot, as advection grows strong enough to break interparticle bonds downstream and drain the wake. In contrast to linear-response rheology that is predictable entirely by B2 for short-ranged attractions, here the non-Newtonian viscosity is not, owing to the additional length scale introduced by the boundary layer. The ratio of external to attractive forces eventually supersedes B2 as the relevant predictor of structure and rheology. This behavior may provide interesting connections to active motion in biological systems where attractive forces are present.

Sticky, active microrheology: Part 1. Linear-response.

Attractive colloidal-scale forces between macromolecules in biological fluids are suspected to play a role in important system dynamics, including association times, spatially heterogeneous viscosity, and anomalous diffusion. Passive and active microrheology provide a natural connection between observable particle motion and viscosity in such systems via generalized Stokes-Einstein and Stokes' drag law relations. While such models are robust for purely repulsive colloidal-scale interactions, no such theory exists to model the effects of attractive forces. Here we present such a model for the linear-response regime, where a Brownian probe particle is driven gently through a complex fluid by an external force that weakly augments thermal fluctuations. As the probe moves through the bath, hard-sphere repulsion results in an accumulation of particles on its upstream face and a trailing depletion zone, producing particle drag that slows the probe. Linear-response viscosity can be inferred constitutively from this speed reduction. One expects attractive forces to make the suspension more viscous, but surprisingly, weak attractions exerted by upstream particles actively pull the probe forward, giving it a "hypoviscous" environment through which it slides more easily. As attractions grow stronger, particles join to the probe in a long-lasting doublet, extracting particles from the upstream region and depositing them behind the probe. At a critical value of the second virial coefficient common to all potentials we studied, the distorted structure reverses direction, and continued growth of attraction strength causes the probe to drag a cluster of density along, dramatically increasing viscosity. But at this transition, the structure is neutral under the balance of attraction and repulsion, allowing the probe to "cloak" itself and move through the bath undetected and unhindered relative to hard-sphere dispersions. This poses an intriguing mechanism by which proteins or other macromolecules may change their surface chemistry in order to alter the viscosity of the surrounding medium to speed their own motion, or simply to pass undetected through a cell.

SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology.

OBJECTIVE: The SCN11A gene encodes the NaV1.9 sodium channel found exclusively in peripheral nociceptive neurons. METHODS: All enrolled participants were evaluated clinically by electrophysiologic studies, DNA sequencing, and punch skin biopsies. RESULTS: All affected family members are afflicted by episodes of pain. Pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyalgia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology. CONCLUSIONS: Unlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy, and neuropathic pain, the Arg225Cys SCN11A in the present study causes predominantly nociceptive pain with minimal features of neuropathic pain and undetectable pathophysiologic changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand the clinical spectrum beyond painful small fiber sensory neuropathy.

Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: a genomic study.

BACKGROUND: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. METHODS: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma. Patients took 20-240 mg osimertinib per day until disease progression or development of intolerable side-effects. Plasma samples were collected every 6 weeks and tumour tissue biopsy was done at study entry and was optional after disease progression. We tested samples for resistance mechanisms, including EGFR-activating, Thr790Met, and Cys797Ser mutations, and assessed associations with overall survival, progression-free survival, and survival after disease progression. FINDINGS: Of 71 patients enrolled in AURA, 53 were eligible for this analysis. Median progression-free survival was 11·1 months (95% CI 8·4-13·9) and overall survival was 16·9 months (11·7-29·1). 47 patients had disease progression. Median overall survival after osimertinib progression was 5·4 months (95% CI 4·1-10·0). Plasma samples were available for 40 patients after disease progression. 12 (30%) of these had the Thr790Met mutation (four of whom also had Cys797Ser mutations). Patients without detectable EGFR-activating mutations in plasma before treatment had the best overall and post-progression survival (22·4 months, 95% CI 15·6-not reached, and 10·8 months, 7·2-not reached, respectively). Loss of the Thr790Met mutation but presence of EGFR-activating mutations in plasma were associated with the shortest progression-free survival (median 2·6 months, 95% CI 1·3-not reached). In 22 post-progression tumour samples, we found one squamous cell and two small-cell transformations. We detected Thr790Met in nine (50%) of 18 samples, Cys797Ser in two (17%) of 12, cMET amplification in five (50%) of ten, BRAF mutation in one (8%) of 13, and KRAS mutation in one (8%) of 13. INTERPRETATION: Heterogeneous resistance mechanisms developed in patients receiving osimertinib. Differences in resistance mechanisms might dictate future development strategies for osimertinib in clinical trials. FUNDING: AstraZeneca, Taiwan Ministry of Science and Technology.

Vinculin forms a directionally asymmetric catch bond with F-actin.

Vinculin is an actin-binding protein thought to reinforce cell-cell and cell-matrix adhesions. However, how mechanical load affects the vinculin-F-actin bond is unclear. Using a single-molecule optical trap assay, we found that vinculin forms a force-dependent catch bond with F-actin through its tail domain, but with lifetimes that depend strongly on the direction of the applied force. Force toward the pointed (-) end of the actin filament resulted in a bond that was maximally stable at 8 piconewtons, with a mean lifetime (12 seconds) 10 times as long as the mean lifetime when force was applied toward the barbed (+) end. A computational model of lamellipodial actin dynamics suggests that the directionality of the vinculin-F-actin bond could establish long-range order in the actin cytoskeleton. The directional and force-stabilized binding of vinculin to F-actin may be a mechanism by which adhesion complexes maintain front-rear asymmetry in migrating cells.

Effect of mitomycin-C on the variance in refractive outcomes after photorefractive keratectomy.

PURPOSE: To compare the variance in manifest refraction spherical equivalent (MRSE) after photorefractive keratectomy (PRK) with mitomycin-C (MMC), PRK without MMC, and laser in situ keratomileusis (LASIK) for the treatment of myopic astigmatism. SETTING: Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, USA. DESIGN: Retrospective case series. METHODS: Patients were classified into 3 groups of preoperative refraction-matched eyes as follows: PRK with MMC 0.02%, PRK without MMC, and LASIK. The preoperative and postoperative MRSE, preoperative corrected distance visual acuity, and postoperative uncorrected distance visual acuity (UDVA) were analyzed. RESULTS: Each group comprised 30 eyes. Follow-up was at least 6 months in the LASIK group and 12 months in the 2 PRK groups. There were no statistically significant differences in the mean preoperative MRSE (P=.95) or postoperative MRSE (P=.06) between the 3 groups. The mean postoperative MRSE was -0.07 diopter (D) ± 0.47 (SD), -0.14 ± 0.26 D, and 0.02 ± 0.25 D in the PRK with MMC 0.02% group, PRK without MMC group, and LASIK group, respectively. The variance in the postoperative MRSE in the PRK with MMC 0.02% group was significantly higher than that in the PRK without MMC group (P=.002) and in the LASIK group (P=.001). There was no statistically significant difference in the mean postoperative UDVA between the 3 groups (P=.47). CONCLUSIONS: Refractive outcomes after PRK for myopia were more variable when MMC 0.02% was used. This should be weighed against the advantage of intraoperative MMC use in reducing haze after PRK.

Mixed confinement regimes during equilibrium confinement spectroscopy of DNA.

We have used a combination of fluorescence microscopy experiments and Pruned Enriched Rosenbluth Method simulations of a discrete wormlike chain model to measure the mean extension and the variance in the mean extension of λ-DNA in 100 nm deep nanochannels with widths ranging from 100 nm to 1000 nm in discrete 100 nm steps. The mean extension is only weakly affected by the channel aspect ratio. In contrast, the fluctuations of the chain extension qualitatively differ between rectangular channels and square channels with the same cross-sectional area, owing to the "mixing" of different confinement regimes in the rectangular channels. The agreement between experiment and simulation is very good, using the extension due to intercalation as the only adjustable parameter.

Low-dose radiation therapy (2 Gy × 2) in the treatment of orbital lymphoma.

PURPOSE: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. METHODS AND MATERIALS: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). RESULTS: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. CONCLUSIONS: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

Higher incidence of head and neck cancers among Vietnamese American men in California.

BACKGROUND: Our aim was to determine the incidence rates of head and neck cancer in Vietnamese Californians compared with other Asian and non-Asian Californians. METHODS: Age-adjusted incidence rates of head and neck cancer between 1988 and 2004 were computed for Vietnamese Californians compared with other racial/ethnic groups by time period, ethnicity, neighborhood-level socioeconomic status (SES), and sex using data from the population-based California Cancer Registry (CCR). Data by smoking and alcohol status were tabulated from the California Health Interview Survey. RESULTS: Vietnamese men had a higher incidence rate of head and neck cancer than other Asian men. Specifically, the laryngeal cancer rate was significantly higher for Vietnamese men (6.5/100,000; 95% confidence interval [CI], 5.0-8.2) than all other Asian men (range, 2.6-3.8/100,000), except Korean men (5.1/100,000; 95% CI, 3.9-6.4). Both Vietnamese and Korean men had the highest percentage of current smokers. Neighborhood SES was inversely related to head and neck cancer rates among Vietnamese men and women. CONCLUSION: The higher incidence rate of head and neck cancer in Vietnamese men may correspond to the higher smoking prevalence in this group. Individual-level data are needed to establish the link of tobacco, alcohol, and other risk factors with head and neck cancer in these patients.

Metabolic effects of fructose 1,6-bisphosphate in normoxic and hypoxic states of MG63 osteosarcoma cells.

Glycolysis is a very important process which contains very intricate steps that play a role in cellular performance and viability. Fructose 1,6-bisphosphate (FBP) is a glycolytic intermediate that has proven to improve cellular conditions under hypoxic and ischemic conditions. Osteoblasts are key regulators of skeletal matrix synthesis and degradation. Thus, considering FBP's positive effects on ameliorating hypoxia-induced injuries, the objective of this study was to determine its effects and comparative effects on osteoblast cells under normoxic and hypoxic states. MG63 osteoblast-like cells were cultured in 24-well culture plates and treated with high, medium and low dosages of FBP at 24, 48, and 72 hours. At the end of each time period, cellular number, damage by a malondialdehyde assay (MDA), and glutathione levels were evaluated. There was a significant increase in cell number for the low level of FBP in normoxia at 48 hours (p < 0.05). For the cells in hypoxia, there was a significant decrease in cell number for the medium level at 48 hours (p < 0.05). At 48 hours there was a significant decrease in cell damage through MDA measurement for the cells in normoxia and hypoxia when compared to the control. Cellular damage was not evident in the supernatant in either oxygen condition for the duration of the study. A significant decrease in glutathione levels was also noted for the cells in hypoxia. Cellular morphology included multiple nucleoli, vacuolated cytoplasm, abnormal cells, and web-like cytoplasm. The results indicate that FBP does protect bone cells exposed to hypoxic injuries, and while doing so, ameliorating the states of the cells in shock.