Alzheimer's disease(AD) is a refractory neurodegenerative disease clinically characterized by memory loss and cognitive and behavioral dysfunction. The main pathological features of AD include neuronal loss, β-amyloid protein(Aβ) deposition and neurofibrillary tangles (NFTs), and numerous studies have shown that these may be triggered by neuronal death and neuroinflammation Receptor-interacting serine/threonine-protein kinase 1(RIPK1) is a serine/threonine kinase present at the intersection of cell death and inflammatory signaling pathways.Studies in recent years have revealed a potential role of RIPK1 on the progress of AD. In this paper, we summarized the links between RIPK1-mediated necroptosis and AD treatment from the aspects of neuronal death, inflammasome activation, blood-brain barrier breakdown and mitochondrial dysfunction, and the targeted treatment of RIPK1, the new findings of RIPK1 inhibitors and ongoing clinical trials, aiming to provide new ideas for the treatment of AD.

Objective:To observe the inhibiting effects of manual acupuncture(MA)on bladder cell apoptosis in rats with diabetic neurogenic bladder(DNB)based on the protein and mRNA expression of B-cell lymphoma-leukemia(Bcl)-2,Bcl-2-associated X(Bax)protein,caspase-3,and the protein expression of α-smooth muscle actin(α-SMA),transforming growth factor(TGF)-β in the bladder tissue. Methods:A DNB rat model was established via intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into a control group,a model group,and an MA group,with 10 rats in each group.For the MA group,MA was applied after modeling.The body mass,fasting blood glucose(FBG),bladder wet weight,and bladder histomorphology were observed.Protein and mRNA expression levels of Bcl-2,Bax,and caspase-3 and the protein expression of α-SMA and TGF-β in the bladder tissue were determined.The apoptotic index of bladder cells was also evaluated. Results:After STZ injection,compared with the control group,the model group and the MA group both showed higher FBG from week 3 and lower body mass from week 9(P<0.05),and had a larger bladder wet weight(P<0.05).Compared with the model group,the MA group showed a smaller bladder wet weight(P<0.05).The histopathological evaluation indicated that MA improved muscle fiber alignment and detrusor cell compensatory hypertrophy in the bladder tissue.In addition,compared with the control group,the apoptotic index increased significantly in the model group and the MA group(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue in the model group and the MA group increased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue decreased significantly(P<0.05).Compared with the model group,the apoptotic index of the MA group decreased significantly(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue decreased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue increased significantly(P<0.05). Conclusion:MA can protect the bladder by inhibiting the excessive apoptosis of bladder cells,which may be related to the down-regulation of Bax and caspase-3 proteins and mRNAs and TGF-β protein expression,and the up-regulation of Bcl-2 protein and mRNA and α-SMA protein expression.

Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.

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.].

Objective:To learn about the iodine nutritional status of children aged 8 - 10 and pregnant women in Zhaoyuan City of Shandong Province, and to provide a basis for prevention and control of iodine deficiency disorders in the future.Methods:In 2008 and 2021, a census method was used to collect drinking water samples from all 724 villages (neighbourhood committee) in Zhaoyuan City. In 2018 and 2022, a multi-stage cluster random sampling method was used to investigate the daily per capita salt intake of residents. From 2017 to 2022, multi-stage random sampling method was used to collect household salt and urine samples from children aged 8 - 10 and pregnant women. Among them, thyroid volume tests were conducted on the sampled children in 2017, 2019, 2020 and 2022, and iodine supplementation surveys were conducted on the sampled pregnant women in 2019 - 2022. The iodine content in water was determined by As 3+-Ce 4+ catalytic spectrophotometry using ammonium persulfate digestion. The iodine content in potassium iodate salt was determined by direct titration method in "General Test Method in Salt Industry-Determination of Iodine" (GB/T 13025.7-2012). And other fortified iodized salt, unqualified iodized salt and non-iodized salt were retested using the redox titration method. Urinary iodine was determined by "Determination of iodine in urine - Part 1: As 3+-Ce 4+ catalytic spectrophotometry" (WS/T 107.1-2016). The children's thyroid gland was examined by using DP-2200Plus fully digital portable ultrasound instrument and 75L38EB ultrasound probe, and the goiter rate was calculated. Results:The median water iodine levels in Zhaoyuan City in 2008 and 2021 were 5.71 and 1.30 μg/L, respectively. The daily per capita salt intake of residents in 2018 and 2022 was 9.36 and 7.83 g, respectively. It is estimated that the per capita iodine intake in 2018 was (180.64 ± 71.00) μg/d and in 2022 was (124.25 ± 72.23) μg/d. From 2017 to 2022, the consumption rate of qualified iodized salt in both children and pregnant women was less than 90%; and from 2018 to 2022, the coverage rate of iodized salt was < 95%. The median urinary iodine of children was 184.00 μg/L, at an appropriate level, there was a statistically significant difference in urinary iodine content among children in different years ( H = 77.39, P < 0.001). From 2017 to 2022, the median urinary iodine of pregnant women was between 100 and 150 μg/L, there was no statistically significant difference in urinary iodine content among pregnant women in different years ( H = 5.33, P = 0.208). The goiter rate of children in 2017, 2019, 2020 and 2022 was 3.00% (24/800), there was no statistically significant difference in goiter rate among children in different years ( P = 1.000). A total of 400 pregnant women were investigated for iodine supplementation, the rate of iodine supplementation was 90.50% (362/400). Conclusions:Zhaoyuan City has reached the elimination standard for iodine deficiency disorders, but some pregnant women are at risk of iodine deficiency. Continuous monitoring and attention should be paid to the iodine nutritional status of pregnant women.

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:This study aimed to compare the detection efficacy of transrectal ultrasound-guided transrectal cognitive fusion targeted+ systematic prostate biopsy and transperineal cognitive fusion targeted + systematic biopsy in patients with suspected prostate cancer (PCa). In addition, the relative clinical characteristics of PCa were evaluated.Methods:A total of 385 patients with suspected prostate cancer in the affiliated hospital of Qingdao University from May 2019 to November 2019 were retrospectively analyzed. All patients met the prostate biopsy criterion, who underwent transrectal(n=275)and transperineal(n=110)prostate biopsy respectively. There were no significant differences of mean age [(70.7±7.3)years vs.(69.2±8.4) years], PSA [(55.12±116.96)ng/ml vs. (63.41±315.34)ng/ml], prostate volume [(55.96±35.26)ml vs. (64.35±55.99)ml] between two groups. According to preoperative prostate magnetic resonance imaging combined with intraoperative ultrasound, 2-4 needles targeted puncture of suspected lesion were performed, followed by 12 needle systematic prostate biopsy. The detection rate of prostate cancer between two biopsy ways were compared. The related factors of PCa including age, prostate volume and PSA level were collected for univariable and multivariable logistic analysis. The cancer detection rate was compared and logistic regression was used to assess the impact of patient characteristics on PCa detection.Results:For all patients, the detection rate with cancer between transrectal group and transperineal group were 121/275(40.0%) and 67/110(60.9%), respectively. The transperineal group detected a higher rate of PCa ( P=0.003)and more clinically significant prostate cancers (csPCa) (54.6% vs.36.7%, P=0.001) than that of the transrectal group, there were significant differences between two groups ( P<0.05). Univariate and multivariate logistic regression analysis revealed that PSA( OR=1.025, P=0.001) and prostate volume( OR=0.984, P=0.001)were two independent factors for the detection rate of prostate cancer between two biopsy ways( P<0.05). The effect of age on the detection rate of PCa in the transperieal group was significantly lower than that of the transrectal group( OR=0.037, P=0.238 vs. OR=0.053, P=0.002). Conclusion:The transperieal biopsy could find more PCa than the transrectal biopsy. PSA level and prostate volume could affect the detection rate of cancer between two prostate biopsy ways.

Objective:To preliminarily estimate and study the effect of nucleic acid testing in blood screening on the residual risk (RR) of transfusion transmitted HBV infection (TTI HBV).Methods:Using the NAT yield/WP ratio model and adopting the relevant data of information management system of practice comparison working party in the Mainland of China, this paper analyzed the trend of the RR of TTI HBV among 18 blood centers from 2015 to 2019 in China, and compared the impact of two kinds of blood screening strategies which were ELISA+ ID-NAT/MP-NAT (individual-donation nucleic acid testing or mini-pool nucleic acid testing) and ELISA + MP-NAT on RR in 2019.Results:The overall trends of the 5-year RR of HBV among 18 blood centers showed by trend chi square test were NAT single positive rate trend χ2= 39.42( P<0.01) and residual risk trend χ2= 279.792( P<0.01); The influence on RR from the differences of ELISA+ ID-NAT/MP-NAT and ELISA+ MP-NAT was statistically significant, and chi square test showed that χ2= 7.4( P<0.01). Conclusions:Since the implementation of nucleic acid testing in the blood screening in China from 2015, the residual risk of transfusion transmitted HBV infection has decreased year by year. The observed two blood screening strategies which dominated in China may lead to discrepancy in the residual risk of TTI.

Objective:To apply the best evidence of non-drug management of chemotherapy induced nausea and vomiting (CINV) in clinical practice, and evaluate the effect of practice.Methods:After searching domestic and foreign databases, 14 articles were finally included, including 3 systematic reviews, 3 evidence summaries and 8 guidelines. According to the evidence-based continuous quality improvement model of Joanna Briggs Institute (JBI) Evidence-based Nursing and Health Care Center, we conducted the review before and after evidence application, obstacle factors, available resources and strategy analysis, and evaluation of the effect of evidence application. From March to May 2020, convenience sampling was used to select 52 inpatients with gynecological chemotherapy in the Affiliated Hospital of Qingdao University and 26 clinical nurses as subjects for baseline review. From June to August 2020, 42 inpatients with gynecological chemotherapy and 26 clinical nurses (same as before) were selected for re-review.Results:The management process, nursing routine, nursing path, and risk assessment and follow-up form for CINV were improved, and an evidence-based education video was produced. After application of the evidence, the compliance of nurses' review indicators improved, and the differences were statistically significant ( P<0.05) . The scores of nurses on the non-drug management evidence-based knowledge questionnaire for gynecological CINV increased, and the difference was statistically significant ( P<0.05) . The incidence of acute CINV decreased, and the difference was statistically significant ( P<0.05) . The incidence of delayed CINV decreased, and the difference was not statistically significant ( P> 0.05) . Conclusions:The development of the evidence-based practice project promotes the improvement of related processes, routines, and paths, enriches the forms and content of CINV non-drug antiemetic education, standardized nurses' behavior, improves nurses' compliance with evidence-based practice, and reduces the incidence of acute nausea and vomiting in patients.