Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

OBJECTIVE: To observe the decay law of chromosome aberrations after 3 years iridium-192 radiation exposure in victims of Nanjing “5.7” radiation accident. METHODS: The peripheral blood of victims was collected 3 years after iridium-192 radiation exposure. The routine chromosome aberration analysis, micronucleus analysis and G-banding karyotype analysis were used to detect the chromosomal instability rate, the binuclear micronucleus rate and the stability distortion rate. A dose reconstruction was carried out based on the distortion results. RESULTS: The aberration frequency of dicentric(dic) and centric rings(r) was 6.5% after 3 years iridium-192 radiation exposure, which decreased to 31.0% at 6 days after exposure(the aberration frequency of dic and r was 21.0%). The estimated biological dose based on the aberration frequency of dic and r was 0.75 Gy, which is about 50.0% of the initial estimated dose(1.52 Gy) at 6 days after exposure. The micronucleus rate of the binuclear lymphocytes was 63.0‰, and the estimated biological dose based on the micronucleus rate was 0.71 Gy, which was similar to the estimated dose of aberration frequency of dic and r. The total frequency of chromosome aberration observed by karyotype analysis of G-bands by trypsin using Giemsa was 41.0%, the stability aberration frequency was 30.0%, and the translocation frequency was 15.0%. The result of dose reconstruction based on the translocation frequency was 1.50-1.89 Gy, which was very close to the initial estimated dose(1.52 Gy). CONCLUSION: The decay of unstable chromosome aberration may be influenced by many factors, more detailed data need to be accumulated to study the decay law. The use of stable chromosomal aberrations, especially translocation frequencies used in dose reconstruction in earlier exposures, is an ideal method.

Objective: To explore the long-term effects of radiation injury and to provide scientific basis for the evaluation of the effects of ionizing radiation injury by carrying out medical follow-up of patients involved in the " 5.7" radiative source accident in Nanjing in 2014. Methods: Through interviewing and investigating, we inquired about the new disease history of the exposed patients from rehabilitation treatment to medical follow-up peroid. Physical and laboratory examinations were carried out. According to relevant standards, physiological and biochemical indexes such as hematopoietic system, immune system, endocrine system, ophthalmology, circulatory system, digestive system, urinary system and bone mineral density were systematically evaluated, with the long-term effects being evaluated. Results: The patient′s vital signs were good without new diseases. The indexes of hematopoietic system, immune system and endocrine system tended to be normal, the circulatory system, digestive system and urinary system showed degenerative changes, the ophthalmic examination showed visual acuity continue to decline, and bone mineral density examination indicated low bone mass. Conclusions Physiological and biochemical indicators of the patients gradually returned to normal without obvious symptoms of radiation damage. Further medical follow-up observation still needs to continue.

Objective To analyze the correlation between treatment time and radiotherapy plan of deep inspiration breath-hold (DIBH) technique for the whole breast irradiation (WBI) in the left breast cancer after breast-conserving surgery,verify the inter-fractional reproducibility of radiotherapy,observe the heart location and dosimetric changes and calculate the effect of DIBH upon the WBI setup error after the surgery.Methods We prospectively enrolled 15 patients with left breast cancer undergoing WBI after breast-conserving surgery,who met the requirement of D1BH.Treatment time was recorded,its correlation with the number of field and monitor unit was analyzed.Inter-fractional setup errors and PTV delineation were calculated using cone beam CT (CBCT).The accuracy of the position and dose of the heart during radiotherapy was verified by the imaging fusion of CBCT and CT images.The variables among groups were analyzed by non-parametric Firedman test.Results The average treatment time of DIBH radiotherapy was 4.6 minutes.The treatment time was correlated with the maximal and total number of sub-fields and total monitor units.During DIBH treatment,the mean cardiac displacement volume was 19.1 cm3(3.8％).The mean cardiac dose difference between CBCT and planning CT was 5.1 cGy,and there was no significant difference in the heart V5-V30.The mean inter-fractional system setup error (∑) and random setup error (σ) in the left-right (x),superior-inferior (y) and anterior-posterior (z) direction were ∑x 1.9 mm,∑y 2.1 mm,∑z 2.0 mm,σx 1.3 mm,σy 1.3 mm,σz 1.4 mm,respectively.The corresponding minimal margins for setup error were 5.7 mm,6.2 mm and 6.0 mm,respectively.Conclusion DIBH for WBI after breast-conserving surgery does not significantly prolong the treatment time.Treatment time is related to treatment plan.DIBH yields high inter-fractional reproducibility and protects the heart.

Objective To investigate the status and influencing factors of infusion-related adverse events in third-party cord blood stem cell infusion. Methods A total of 305 patients successfully underwent haploidentical stem cell transplantation combined with the third-party cord blood(CB) infusion,were recruited by convenience sampling from January 2013 to December 2015,in hematological department of a tertiary hospital in Suzhou. A self-developed questionnaire and adverse event assessment scale were used to investigate the influencing factors. Results The rate of infusion-related adverse events was 49.51%,81.82% were related to cardiovascular adverse events with the high-est rate of hypertension(76.14%). Logistic regression analysis showed that age(OR=1.030,95CI%:1.010-1.051),HLA matching between CB and receptor (OR=0.589,95%CI:0.413-0.838),thawed CB cell activity (OR=1.064,95%CI:1.015-1.115)were major influencing factors. Conclusion Nurses should pay attention to patients who are elderly,with low matching HLA and receive thawed CB product with high cell activities,and provide timely nursing care in advance.

Objective To observe the Alberta combined with Infant Language Assessment Scale used in rehabilitation for children with cerebral palsy.Methods From Jun.2012 to Jun.2013,64 cases of cerebral palsy in Children's Hospital Affiliated to Suzhou University were selected according to the different interventions and were randomly divided into an observation group and a control group,32 patients in each group.The control group underwent conventional rehabilitation training included exercise therapy (mainly Bobath therapy,Ueda therapy) and application Infants Language Assessment Scale for treatment,and the observation group on the basis of the method above,set the action in accordance with Alberta infant motor scale(AIMS) assessment to develop rehabilitation programs.Adhere to 3 hours a day of repeated intensive training.Efficacy in children after treatment was compared,and forceful move and fine motor movements and the changes in development quotient(DQ) before and after treatment were compared between 2 groups.Results The total efficiency of the observation group and the control group was 90.6％ and 71.9％,respectively,and there was statistically significant differences between 2 groups (x2 =6.317,P ＜ 0.05).After treatment,the DQ of big movement and fine motor in observation group (47.92 ± 7.15,42.55 ± 8.1 3) were significantly higher than before treatment (36.18 ± 8.23,33.71 ± 10.16) and the control group (38.13 ± 8.21,36.58 ± 8.06),the differences were statistically significant(t =6.235,5.452,6.137,5.243,all P ＜ 0.05).Conclusions The combination of the rehabilitation for children with cerebral palsy in infants language Alberta combined score rating scale,help to improve rehabilitation results and motor function in children,which is of recommendation and application.

Currently,three predominant subtypes of influenza virus are prevalent in pig populations worldwide:H1N1,H3N2,and H1N2.European avian-like H1N1 viruses,which were initially detected in European pig populations in 1979,have been circulating in pigs in eastern China since 2007.In this study,six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China.Based on whole genome sequencing,molecular characteristics of two isolates were determined.Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations,especially similar to those found in China.Four potential glycosylation sites were observed at positions 13,26,198,277 in the HA1 proteins of the two isolates.Due to the presence of a stop codon at codon 12,the isolates contained truncated PB1-F2 proteins.In this study,the isolates contained 591Q,627E and 701N in the polymerase subunit PB2,which had been shown to be determinants of virulence and host adaptation.The isolates also had a D rather than E at position 92 of the NS1,a marker of mammalian adaptation.Both isolates contained the GPKV motif at the PDZ ligand domain of the 3' end of the NS1,a characteristic marker of the European avian-like swine viruses since about 1999,which is distinct from those of avian,human and classical swine viruses.The M2 proteins of the isolates have the mutation (S31N),a characteristic marker of the European avian-like swine viruses since about 1987,which may confer resistance to amantadine and rimantadine antivirals.Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs,and raise more concerns about the occurrence of cross-species transmission events.

Objective To explore the method and management of pre-hospital care and raise the level of traffic injuries in pre-hospital care by summarizing the clinical features of death patients with severe tragic accident trauma Methods The basic data of 62 death patients with severe traffic accident trauma was analyzed according to death report statistics of severe traffic accident trauma from January 1st,2005 to December 31th,2008 Results Brain injury death accounted for most of traffic accident trauma death.The mortality rate of brain injury in the wounded wag 8.28%(13/157),but of asphyxia and hemorrhagic shock was 2.55%(4/157),3.18%(5/157)respectively in 2005.With the development of treatment and rescued in time, the mortality rate reduced to 6.11%(11/180),0,0.56%(1/180)in 2008.Conclesions It should be trying to shorten the time of pre-hospital care for pafients with trsffic accident trauma,especially in patients combined with hemorrhagic shock,asphyxia,severe brain injury.It is concluded that rapid and effective pre-hospital care can significantly reduce death rate and self-help or each other rescue training would also be effective to reduce mortality.