The treatment of inner ear disease is developing towards local drug delivery to avoid drawbacks of systemic approach.The cochlear implants with drug delivery functions,a newly developed method of drug delivery into inner ear for treatment,has become the focus of research in recent years.In this review,we will describe recent advances in characteristics,product developments and applications of different types of drug loaded cochlear implants for local therapy.

Objective To analyze the daily quality assurance(QA)measurement results of IBA Sphinx Compact device on the Mevion compact pencil beam scanning proton therapy system for evaluating its clinical application value in proton therapy.Methods The daily QA measurement of Mevion S250i proton therapy system was carried out with Sphinx Compact device for 30 consecutive days,and the measurement results were analyzed.Results The average deviation between the positioning laser and the image center was(0.42±0.27)mm in 30 days.All of the proximal and distal depth errors of the high-and low-energy pencil beams were within 0.50 mm.The position deviation of all the spots measured did not exceed 1.00 mm,and the size deviation was less than 7.5%.The deviation between the image center and the beam center was not more than 0.75 mm.The relative deviation of the flatness of the rectangular field was about 0.5%.The deviation of the output dose of the square field was within 1.0%.Conclusion The proton system daily QA measurement items recommended by AAPM TG-224 report can be accurately and rapidly measured with Sphinx Compact device.The device is a practical and efficient daily QA tool with high practical value in clinic.

OBJECTIVE To establish a database of rational drug use for children in our hospital， and to provide reference for ensuring the safety of drug use in children. METHODS The construction and filling of the knowledge base of rational drug use for children were performed by establishing the basic structure of the knowledge base， formulating reference standards for the quality level of pediatric medication evidence， and refining evidence-based evidence of pediatric medication. The rule base of rational drug use for children was designed and built from four aspects： preliminary determination rules for patient information， basic drug information rules， prescription suitability review rules， result labeling and post-processing rules. The database was embedded into prescription review system of our hospital and was applied online to test its effectiveness. RESULTS A set of database containing 672 commonly used pediatric medicines and more than 15 000 rules for rational drug use for children was initially constructed. The average interception rate of unreasonable medical orders for hospitalized children after database application（from December 2021 to May 2022）was 2.03%， and was higher than 0.80% before database application（from June 2021 to November 2021）（χ 2＝5 784.389， P＜0.001）； after post-sampling and prescription review， the average qualified rate of medication orders in discharged medical records for children after the application of the database was 99.10%， and was higher than 94.58% before the application of the database （χ 2＝301.237， P＜0.001）. CONCLUSIONS Self-constructed evidence-based rational drug use database for children is close to the actual clinical needs of pediatrics in medical institutions， which can effectively reduce clinical irrational drug use behaviors in pediatrics， improve the pass rate of prescriptions， and ensure the safety of children’s drug use.

Delayed diabetic wound healing has placed an enormous burden on society. The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis. Platelet-rich plasma (PRP) gel, a popular biomaterial in the field of regeneration, has limited applications due to its non-injectable properties and rapid release and degradation of growth factors. Here, we prepared an injectable hydrogel (DPLG) based on PRP and laponite by a simple one-step mixing method. Taking advantages of the non-covalent interactions, DPLG could overcome the limitations of PRP gels, which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine (an angiogenesis promoter). DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in type I diabetic rats and normal rats. Taken together, this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study. However, few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy. In this study, a decreased level of SNX3 in Dox-induced cardiomyopathy was observed. Cardiac-specific Snx3 knockout (Snx3-cKO) significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly. SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro, and cardiac-specific Snx3 transgenic (Snx3-cTg) mice were more susceptible to Dox-induced ferroptosis and cardiomyopathy. Mechanistically, SNX3 facilitated the recycling of transferrin 1 receptor (TFRC) via direct interaction, disrupting iron homeostasis, increasing the accumulation of iron, triggering ferroptosis, and eventually exacerbating Dox-induced cardiomyopathy. Overall, these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRC-dependent ferroptosis.

Objective:To compare the early therapeutic effects of internal fixation with percutaneous minimally invasive hollow nail assisted by electromagnetic navigation robot and guided by C-arm in the treatment of Tile type C pelvic fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 32 patients with Tile type C pelvic fracture admitted to Weihai Central Hospital from January 2020 to March 2022, including 18 males and 14 females; aged 36-60 years [(44.1±3.9)years]. Among them, 17 patients were treated with internal fixation with percutaneous minimally invasive hollow nail assisted by electromagnetic navigation robot (electromagnetic navigation group), and 15 with internal fixation with percutaneous minimally invasive hollow nail guided by C-arm (C-arm guidance group). Operative time, intraoperative blood loss, sacroiliac screw placement time, pubic branch screw placement time, ambulation time and fracture healing time were compared between the two groups. Visual analog scale (VAS), Majeed function score and complication rate at 1 day, 6 months, 12 months after surgery and at the last follow-up were compared between the two groups.Results:All the patients were followed up for 12-24 months [(15.4±0.5)months]. The operative time and intraoperative blood loss in the electromagnetic navigation group were (42.0±2.5)minutes and (10.9±2.6)ml, shorter or less than (50.0±3.5)minutes and (14.9±3.1)ml in the C-arm guidance group (all P<0.01). The placement time of sacroiliac screw and pubic branch screw in the electromagnetic navigation group was (12.4±0.2)minutes and (10.1±0.3)minutes, shorter than (15.3±0.3)minutes and (13.2±0.3)minutes in the C-arm guidance group (all P<0.01). The ambulation time was (3.2±0.4)weeks in the electromagnetic navigation group, earlier than (3.5±0.4)weeks in the C-arm guidance group ( P<0.05). There was no significant difference in fracture healing time between the two groups ( P>0.05). VAS scores of the electromagnetic navigation group were (4.4±0.3)points and (1.1±0.1)points at 1 day and 6 months after surgery respectively, lower than those of the C-arm guidance group [(4.8±0.4)points and (1.2±0.3)points] ( P<0.05 or 0.01). Majeed function scores of the electromagnetic navigation group were (37.3±1.1)points and (88.5±1.4)points at 1 day and 6 months after surgery respectively, higher than those of the C-arm guidance group [(30.7±4.2)points and (82.6±1.8)points] (all P<0.01). There were no significant differences in VAS and Majeed scores at 12 months after surgery and at the last follow-up between the two groups (all P>0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared with C-arm guidance, electromagnetic navigation robot-assisted internal fixation with percutaneous minimally invasive hollow nail for Tile type C pelvic fracture can reduce operative time and intraoperative blood loss, shorten screw placement time and ambulation time, relieve pain and improve functional recovery at early stage.

OBJECTIVES: Cerebral infarction is a subtype of stroke with high incidence and disability rate. Ischemia reperfusion injury (IRI) is the key point of cerebral infarction treatment. UbiA prenyltransferase domain containing 1 (UBIAD1) is a kind of enzyme with various biological functions including electron transport in mitochondrial respiratory chain, lipid metabolism, and oxidative stress which are related to IRI. The purpose of this study aims to determine the neuroprotective effects and the underlying mechanisms of UBIAD1 in cerebral IRI. METHODS: We employed oxygen-glucose deprivation/reoxygenation (OGD/R) model in mouse neuroblastoma Neuro2a (N2a) cells to mimic cerebral IRI. Lentivirus vector over-expressed UBIAD1 was transfacted into N2a cells to maintain high and stable expression of UBIAD1. In the first part of the experiment, N2a cells were divided into 5 groups: A non-OGD (N2a cells without exposure to OGD) group, groups of reoxygenation 0, 4, 12 and 24 h after 4 h of OGD, respectively. In the second part of the experiment, N2a cells were divided into 6 groups: A Con (normal cell)+non-OGD group, an EV (cell transfected with empty vector)+non-OGD group, an OE (over-expressed UBIAD1)+non-OGD group, a Con+OGD/R group, an EV+OGD/R group, and an OE+OGD/R group. In the third part, the N2a cells were divided into 8 groups: A Con+non-OGD group, an OE+non-OGD group, a Con+non-OGD+nNOS inhibitior 7-nitroindazole (7-NI) group, an OE+non-OGD+7-NI group, a Con+OGD/R group, an OE+OGD/R group, a Con+OGD/R+7-NI group, and an OE+OGD/R+7-NI group. The morphological changes of Golgi apparatus were observed under the confocal laser scanning microscope. The mRNA and protein levels of UBIAD1, secretory pathway Ca²⁺-ATPase isoform 1 (SPCA1), and NOS were determined by real-time PCR and Western blotting, respectively. Cell apoptosis rate was detected with flow cytometry; cell viability was detected with MTT assay, and NO release was determined with Griess assay. RESULTS: Compared with the non-OGD group, the expression levels of UBIAD1 mRNA and protein in N2a cells in the groups of 0, 4, 12 and 24 h reoxygenation after OGD 4 h decreased significantly (P<0.05 or P<0.01), and the longer the reoxygenation time, the more significant the reduction of UBIAD1 expression. Compared with the Con+OGD/R group and the EV+OGD/R group, mRNA and protein levels of UBIAD1 and SPCA1 were increased (P<0.05 or P<0.01), the apoptosis rate was decreased (all P<0.01), and the cell viability was increased (all P<0.01) in the OE+OGD/R group. The Golgi fragmentation was less in the OE+OGD/R group than that in the Con+ OGD/R group and the EV+OGD/R group. The mRNA and protein levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) were decreased (P<0.05 or P<0.01), and the level of NO was decreased (all P<0.01) in the groups over-expressed UBIAD1 (OE+non-OGD group vs Con+non-OGD group, OE+OGD/R group vs Con+OGD/R group). The level of NO and apoptosis rate of N2a cells were decreased (all P<0.01) in the the groups pretreated with 7-NI (Con+OGD/R+7-NI group vs Con+OGD/R group, OE+OGD/R+7-NI group vs OE+OGD/R group). CONCLUSIONS UBIAD1 may exerts protective effects on OGD/R induced N2a cells by ameliorating Golgi apparatus dysfunction via the nNOS/NO pathway.
Animals ; Mice ; Cell Survival ; Cerebral Infarction ; Dimethylallyltranstransferase ; Glucose ; Lipid Metabolism ; Oxygen ; Nitric Oxide/metabolism*

Objective: To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports. Methods: Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated. Results: A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated. Conclusions The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).

Objective:To compare the clinical efficacy, prognosis and complications between intravenous chemotherapy (IVC) combined with intra-arterial chemotherapy (IAC) and single IAC in the treatment of children retinoblastoma (RB).Methods:A cohort study was performed.A 4-year follow-up of 300 children (352 eyes) with intraocular RB enrolled in the Children's Hospital Affiliated of Zhengzhou University from June 2015 to June 2019 was conducted.According to the different treatment methods, the children were divided into IAC group (140 cases, 160 eyes) treated with IAC combined with local laser photocoagulation/cryotherapy and IVC+ IAC group (160 cases, 192 eyes) receiving IVC combined with IAC treatment.The clinical efficacy (eye salvage rate), survival and complication incidence of the two groups were compared.The survival analysis was performed by Kaplan-Meier method.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Children's Hospital Affiliated of Zhengzhou University (No.20150503). Written informed consent was obtained from custodians of each child prior to their entering into the cohort.Results:All of the children were followed up for 2-60 months.Within the follow-up, the eye retention rate of the IAC group and IVC+ IAC group was 85.62%(137/160) and 81.21%(154/192) respectively, without statistically significant difference ( P>0.05). The recurrence rate and metastasis rate of IAC group were 18.75%(30/160) and 8.57%(12/140), which were significantly higher than 10.94%(21/192) and 3.13%(5/160) of IVC+ IAC group ( χ2=4.299, P=0.038; χ2=4.143, P=0.042). There was no significant difference in one-year survival rate between the two groups ( χ2=1.766, P=0.184), but the overall survival rate of IVC+ IAC group was 95.00%(152/160), significantly higher than 88.57%(124/140) of IAC group ( χ2=4.193, P=0.041). Kaplan-Meier analysis showed that the overall recurrence-free, metastasis-free and survival rate of IVC+ IAC group were better than those of IAC group, and the differences were statistically significant (all at P<0.05). There was no significant difference in the incidence of eyelid edema and/or ptosis, fundus hemorrhage, enophthalmos and cataract between the two groups (all at P>0.05). The incidence of myelosuppression was 32.14%(45/140) in IAC group, significantly lower than 43.75%(70/160) of IVC+ IAC group ( χ2=4.255, P=0.039). Conclusions:Compared with single IAC treatment, IVC combined with IAC can reduce the metastasis rate, recurrence rate in RB child patient and improve the survival rate, but it is with relatively high incidence of systemic complications.