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.

Objective:To compare the differences of actual absorbed doses of liver malignant tumors after 90Y-selective internal radiation therapy (SIRT) evaluated by 90Y PET/CT and 90Y bremsstrahlung (BRS) SPECT/CT imaging, and to compare the image quality of the 2 imaging methods. Methods:Twenty-one patients (15 males and 6 females; age: (52.4±15.4) years) with liver malignant tumors (15 cases of primary liver cancer, 6 cases of liver metastases; 39 lesions) between September 2021 and August 2022 were retrospectively analyzed. All patients underwent both 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging in the Department of Nuclear Medicine, Hainan Cancer Hospital. The ratios of the actual absorbed doses based on 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging to the lowest standard absorbed dose(100 Gy) for tumor response were calculated. The image contrast and distinguishability of the two imaging methods were scored. Wilcoxon signed rank test and Wilcoxon rank sum test were used for data analysis. Results:The tumor absorbed doses evaluated by 90Y PET/CT and 90Y BRS SPECT/CT were 143.94(55.91, 233.48) Gy and 107.82(53.59, 157.53) Gy respectively. The doses evaluated by 90Y PET/CT were higher than the standard threshold in 24 lesions, while 19 lesions showed higher evaluated doses by 90Y BRS SPECT/CT than the standard threshold. Compared with 90Y PET/CT, 90Y BRS SPECT/CT underestimated the tumor absorbed dose of -24.25%(-32.32%, -12.14%). The ratio of dose evaluated by 90Y PET/CT to the lowest standard threshold was 1.33(0.56, 1.91), which was higher than that of dose evaluated by 90Y BRS SPECT/CT to the lowest standard threshold (0.97(0.47, 1.25); z=0.04, P<0.001). PET/CT image contrast was scored 0, 1, 2, 3 in 2, 2, 12, 23 lesions respectively, and SPECT/CT image contrast was scored 0, 1, 2, 3 in 2, 3, 16, 18 lesions respectively ( z=-1.29, P=0.199). The distinguishability scores of 0, 1, 2 based on PET/CT images were found in 3, 15, 21 lesions, while those based on SPECT/CT images were found in 4, 32, 3 lesions respectively ( z=-2.79, P=0.005). Conclusion:90Y PET/CT imaging is superior to 90Y BRS SPECT/CT imaging in radiation dose evaluation and tumor focus differentiation in patients with liver malignant tumors after 90Y-SIRT.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.

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.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Objective    To compare the short- and long-term efficacy of surgery and endoscopy in the treatment of early esophageal cancer by a systematic review and meta-analysis. Methods    We extracted data independently from The Cochrane Library, PubMed, EMbase, Web of Science for studies comparing surgery with endoscopy from 2010 to 2020. The primary outcomes including R0 resection rate, long-term overall survival (OS), disease-specific survival (DSS), major complications, recurrence, hospital stay and cost. Meta-analysis was performed using RevMan 5.3 and Engauge Digitizer was used to extract survival curves from relevant literature, and relevant data were calculated based on statistical methods. Results    A total of 17 studies involving 3 705 patients were included. It was found that patients in the surgery group had a higher R0 resection rate compared with the endoscopic group (OR=0.13, 95%CI 0.07 to 0.27, P<0.001, I2=6%). The total complications rate of resection of esophageal cancer was higher than that of the endoscopic group (OR=0.28, 95%CI 0.16 to 0.50, P<0.001, I2=68%). The length of hospitalization in the endoscopic group was obviously shorter than that in the surgery group (MD=–8.28, 95%CI –12.44 to –4.13, P<0.001, I2=96%). The distant recurrence rate (OR=0.58, 95%CI 0.24 to 1.41, P=0.230, I2=0%) and the local recurrence rate after resection (OR=1.74, 95%CI 0.66 to 4.59, P=0.260, I2=40%) in the endoscopic group was similar to those of the surgery group. There was no significant difference in 5 year-OS rate between the two groups (HR=0.86, 95%CI 0.67 to 1.11, P=0.25, I2=0%), which was subdivided into two groups: adenocarcinoma (HR=0.55, 95%CI 0.15 to 2.05, P=0.37, I2=0%) and squamous cell carcinoma (HR=0.68, 95%CI 0.46 to 1.01, P=0.06, I2=0%), showing that there was no difference between the two subgroups. There was no significant difference in the DSS rate (HR=0.72, 95%CI 0.49 to 1.05, P=0.090, I2=0%) between the two groups. The cost of the surgery group was significantly higher than that of the endoscopic group (MD=–12.97, 95%CI –18.02 to –7.92, P<0.001, I2=93%). Conclusion    The evidence shows that endotherapy may be an effective treatment for early esophageal neoplasm when considering the long-term outcomes whether it is squamous or adenocarcinoma, even though it is not as effective as surgery in the short-term efficacy.

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 evaluate the current situation and implementation effect of the pilot project of electronic prescription and remote pharmaceutical care in social pharmacy from the perspective of consumers ，and to provide reference for improving and optimizating the electronic prescription and remote pharmaceutical care in social pharmacy. METHODS ：Totally 264 consumers in 6 counties and 36 drugstores of Chengdu were randomly selected for the questionnaire survey. Descriptive statistics were conducted by using SPSS 23.0 software. Compare the distribution and differences of various. The influential factors in consumer satisfaction based on χ2 test and ordinal multiple Logistic regression analysis. Consumers were randomly selected for semi-structured interviews. Text analysis was conducted by Nvivo 12.0 software to refine the problem of this service . RESULTS ：A total of 271 questionnaires were distributed to consumers in various districts of Chengdu ，and 264 valid questionnaires were collected，with an effective recovery rate of 97.4％. Among 264 respondents，178（67.9％）knew about electronic prescription and remote pharmaceutical care ；197（74.6％）received electronic prescription and remote pharmaceutical care service in pharmacies ； 202（76.5％）said they needed this service ，and 63（23.9％）expressed that they would like to pay for it. Of the 197 respondents who had received the service ，163（82.2％）were satisfied or very satisfied with the service ，and only one （0.5％）was dissatisfied with the service. Waiting time ，satisfaction of drug demand ，staff attitude ，service platform configuration ，the qualifications of tele-practice pharmacists and service quality were the main influential factors of satisfaction ；while the service also suffered from difficulties in electronic prescription circulation ，inadequate service monitoring measures ，insufficient certification of physicians and pharmacists，cultural lag ，and irregular service processes. CONCLUSIONS ：Electronic prescription and remote pharmaceutical care service in social pharmacy is inadequate in terms of technical level ，institutional design and social acceptance. It is recommended that relevant departments implement incentive policies ，optimize technology ；follow up supporting policies in time ，strengthen supervision；and increase social publicity and supervision ，so as to promote the continuous improvement and long-term development of electronic prescription and remote pharmaceutical care in social pharmacy.