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Lattice anionic (oxygen) redox reactions (ARR) offers opportunities for developing high-capacity batteries, however, often suffers the notoriously high hysteresis in voltages and low initial coulombic efficiency. Particularly, ARR was widely considered inherent to these kinetic issues. In this paper, unambiguous evidences of strong and reversible ARR is found in Na2/3Ni1/3Mn2/3O2 through mapping of resonant inelastic X-ray scattering (mRIXS). Strikingly, the material displays negligible voltage hysteresis (0.1 V) and high initial coulombic efficiency with a highly stable electrochemical profile. Our independent analysis of the Ni, Mn and O states consistently interpret the redox mechanism of Na2/3Ni1/3Mn2/3O2, which reveals a strong ARR system with facile kinetics and highly stable electrochemical profile that previously found only in cationic redox systems of conventional non-Alkali-rich materials.

Realizing reversible reduction-oxidation (redox) reactions of lattice oxygen in batteries is a promising way to improve the energy and power density. However, conventional oxygen absorption spectroscopy fails to distinguish the critical oxygen chemistry in oxide-based battery electrodes. Therefore, high-efficiency full-range mapping of resonant inelastic X-ray scattering (mRIXS) has been developed as a reliable probe of oxygen redox reactions. Here, based on mRIXS results collected from a series of Li1.17Ni0.21Co0.08Mn0.54O2 electrodes at different electrochemical states and its comparison with peroxides, we provide a comprehensive analysis of five components observed in the mRIXS results. While all the five components evolve upon electrochemical cycling, only two of them correspond to the critical states associated with oxygen redox reactions. One is a specific feature at 531.0 eV excitation and 523.7 eV emission energy, the other is a low-energy loss feature. We show that both features evolve with electrochemical cycling of Li1.17Ni0.21Co0.08Mn0.54O2 electrodes, and could be used for characterizing oxidized oxygen states in the lattice of battery electrodes. This work provides an important benchmark for a complete assignment of all mRIXS features collected from battery materials, which sets a general foundation for future studies in characterization, analysis, and theoretical calculation for probing and understanding oxygen redox reactions.

Zongbo Zhao,&ast; Jianzhong Xue,&ast; Ziliang Zhuo, Wei Zhong, Hui Liu Department of Neurology and Institute of Neurology, The Affiliated Changshu Hospital of Xuzhou Medical University, Suchow, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Liu, Tel/Fax +860512-52925530, Email laoniu20201111@163.comObjective: To investigate the association between IL7R rs6897932 and multiple sclerosis (MS) in southern Chinese people.Methods: In total, 147 MS patients and 530 healthy controls were recruited according to the revised McDonald criteria. The TaqMan method was used for genotyping.Results: With genetic models, we can observe that the additive model, the dominant model, and the recessive model of IL7R rs6897932 were significantly associated with MS [additive model: p=0.032; dominant model (adjusted): p< 0.001, OR=3.61 (95% CI 2.25– 5.83); recessive model (adjusted): p< 0.001, OR=6.80 (95% CI 3.49– 13.89)].Conclusion: Our results suggest that IL7R rs6897932 is associated with MS in a southern Chinese population. More and larger MS studies to explore the genetic risk factors of MS are warranted.Keywords: single-nucleotide polymorphism, multiple sclerosis, IL7R, interleukin

The reversibility and cyclability of anionic redox in battery electrodes hold the key to its practical employments. Here, through mapping of resonant inelastic X-ray scattering (mRIXS), we have independently quantified the evolving redox states of both cations and anions in Na 2/3 Mg 1/3 Mn 2/3 O 2 . The bulk Mn redox emerges from initial discharge and is quantified by inverse partial fluorescence yield (iPFY) from Mn-L mRIXS. Bulk and surface Mn activities likely lead to the voltage fade. O-K super-partial fluorescence yield (sPFY) analysis of mRIXS shows 79% lattice oxygen redox reversibility during the initial cycle, with 87% capacity sustained after 100 cycles. In Li 1.17 Ni 0.21 Co 0.08 Mn 0.54 O 2 , lattice oxygen redox is 76% initial-cycle reversible but with only 44% capacity retention after 500 cycles. These results unambiguously show the high reversibility of lattice oxygen redox in both Li-ion and Na-ion systems. The contrast between Na 2/3 Mg 1/3 Mn 2/3 O 2 and Li 1.17 Ni 0.21 Co 0.08 Mn 0.54 O 2 systems suggests the importance of distinguishing lattice oxygen redox from other oxygen activities for clarifying its intrinsic properties. Battery cathodes based on 3d-transition-metal oxides need viable improvements in their energy density. Recent proposals of O redox have enabled conceptual possibilities, although the assessment of its reversibility remains elusive. This work reports independent and direct quantifications of the evolving O-2p and Mn-3d redox states through O-K and Mn-L mapping of resonant inelastic X-ray scattering (mRIXS). The high reversibility of the lattice O redox in Na 2/3 Mg 1/3 Mn 2/3 O 2 (79%) and Li 1.17 Ni 0.21 Co 0.08 Mn 0.54 O 2 (76%) is revealed during the initial cycle. While Na 2/3 Mg 1/3 Mn 2/3 O 2 displays decent O-redox capacity retention (87% after 100 cycles), the Li-rich system shows significant decay (44% after 500 cycles). We demonstrate direct quantifications of the reversibility of lattice O redox through photon-in-photon-out bulk-sensitive mRIXS. The quantification results directly show that the reversibility of lattice O redox could be very high in both Li-ion and Na-ion batteries. Reversibility of lattice oxygen redox holds the key to its practical employments, especially in 3d transition-metal compounds. Here, direct, independent, and quantitative bulk probes of both cationic and lattice anionic redox chemistry are achieved through mapping of resonant inelastic X-ray scattering. We found highly reversible lattice oxygen redox in Na 2/3 Mg 1/3 Mn 2/3 O 2 (79%) and Li 1.17 Ni 0.21 Co 0.08 Mn 0.54 O 2 (76%) during the initial cycle, with 87% and 44% capacity retention after 100 and 500 cycles, respectively. Therefore, aside from other oxygen activities, lattice oxygen redox could be highly reversible in batteries.

Yue Qiu,1,&ast; Daojiong Lin,2,&ast; Yi Xu,3,&ast; Yibing Cheng,4 Fang Wang,5 Qingxiong Zhu,6 Chunhui Zhu,6 Chaomin Wan,7 Yu Zhu,7 Jianning Tong,8 Rui Li,8 Qionghua Zhou,2 Minxia Chen,3 Qingwen Shan,9 Zhiqiang Zhuo,10 Caihong Wang,10 Shiyong Zhao,11 Wen Song,11 Mei Zeng1 1Department of Infectious Diseases, Children’s Hospital of Fudan University, ShangHai, People’s Republic of China; 2Department of Infectious Diseases, Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China; 3Department of Infections Disease, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 4Department of Emergency, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 5Department of Infections Disease, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 6Department of Infection Diseases, Children’s hospital of Jiangxi Province, Nanchang, People’s Republic of China; 7Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Department of Pediatric, Gastroenterology and Infectious Diseases, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China; 9Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 10Department of Infectious Diseases, Xiamen Children’s Hospital, Xiamen, People’s Republic of China; 11Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei ZengDepartment of Infectious Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, People’s Republic of ChinaTel +86-21-64931132Email zengmeigao@aliyun.comObjective: To assess clinical characteristics, outcomes and antimicrobial resistance of invasive Klebsiella pneumoniae (KP) infections in Chinese pediatric patients in hospital and community settings.Methods: This retrospective study was conducted in the nine tertiary hospitals during 2016– 2018. The 324 pediatric inpatients who had KP isolated from blood and cerebrospinal fluid and had complete medical records reviewed were included. We analyzed the risk factors, outcomes and antimicrobial resistance pattern of KP-infected patients based on comparison between healthcare-associated KP infections (HAI) and community-acquired infections.Results: Of the 324 enrolled patients, 275 (84.9%) were clinically defined as HAI, including 175 (63.6%) neonates and 100 (36.4%) aged > 28 days. The overall prevalence of CRKP was 38.2% (43.4% in HAI verse 8.7% in CAI, P < 0.05). Prematurity (odds ratio (OR): 37.07, 95% CI: 8.29– 165.84), hematologic malignancies (OR: 15.52, 95% CI: 1.89– 127.14) and invasive mechanical ventilation (OR: 13.09, 95% CI: 1.66– 103.56) were independent risk factors for HAI. Patients from rural area (OR: 1.94, 95% CI: 1.12– 3.35), invasive mechanical ventilation (OR: 2.33, 95% CI: 1.25– 4.33), antibiotic therapy prior to admission (OR: 2.33, 95% CI: 1.25– 4.33) and prior hospital stay in the past 30 days (OR: 3.46, 95% CI: 1.87– 6.41) were associated with healthcare-associated CRKP infections. Organ dysfunction was independently correlated with poor outcomes (OR: 2.92, 95% CI: 1.23– 6.95).Conclusion: Pediatric invasive KP infections and high prevalence of CRKP infections largely occurred in healthcare settings in China. The adequate and intensified infection control measures should be focused on high-risk hematologic patients, neonatal patients and intubated patients.Keywords: Klebsiella pneumoniae, healthcare-associated infections, children

We performed a comparative study of the soft x-ray absorption spectroscopy of the LiMn2O4 and Li1.15Mn1.85O4 electrode materials with a quantitative analysis of Mn oxidation states. The revealed redox evolution of Mn upon electrochemical cycling clarifies the effect of excess Li in the materials, which naturally explains the different electrochemical performance. The spectral analysis perfectly agrees with different initial cycling capacities of the two materials. The results show unambiguously that Mn3+ starts to dominate the electrode surface after only one cycle. More importantly, the data show that, while LiMn2O4 electrodes follow the nominal Mn redox evolution, the formation of Mn3+ on the electrode surface is largely retarded for Li1.15Mn1.85O4 during most of the electrochemical processes. Such a different surface Mn redox behavior leads to differences in the detrimental effects of Mn2+ formation on the surface, which is observed directly after only two cycles. Our results provide strong evidence that a key effect of the (bulk) excess Li doping is actually due to processes on the electrode surfaces.

Yuxiang Liao,1 Li Yuan,2 Zhiping Zhang,1 Ao Lin,3 Jingying Zhou,4 Zhenjian Zhuo,3 Jie Zhao1 1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Changsha, People’s Republic of China; 2Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China; 3Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China; 4Department of Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, People’s Republic of ChinaCorrespondence: Jie ZhaoDepartment of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, People’s Republic of ChinaEmail steelzj@csu.edu.cnZhenjian ZhuoDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, Guangdong, People’s Republic of ChinaTel +86-13510841053Email zhenjianzhuo@163.comBackground: Central nervous system (CNS) tumor is a malignancy commonly seen occurring in childhood, worldwide. Fat mass and obesity-associated (FTO) enzyme, initially identified as an obesity-related protein, also functions as a susceptibility gene for cancers. However, predisposing effect of FTO gene single nucleotide polymorphisms (SNPs) on CNS tumor risk remains unknown.Methods: Herein, we genotyped 314 CNS tumor patients and 380 healthy controls samples from three hospitals to explore whether FTO gene SNPs impact CNS tumor risk. TaqMan SNP genotyping assay was applied for the genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from multinomial logistic regression, were applied to determine the associations of SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G) in FTO gene with risk of CNS tumor.Results: We failed to detect significant associations between FTO gene SNPs and CNS tumor risk, either in single-locus or combined analysis. A significantly increased ependymoma risk was found for carriers with 3– 4 risk genotypes in comparison to 0– 2 risk genotypes (adjusted OR=1.94, 95% CI=1.11– 3.37, P=0.020).Conclusion: Our data indicated that FTO gene SNPs are unlikely to have large effects on CNS tumor risk but may have weaker effects.Keywords: CNS tumor, risk, FTO, polymorphism, Chinese

Yi Zheng,* Zhenjian Zhuo,* Xiaoli Xie, Lifeng Lu, Qiuming He, Wei Zhong Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei ZhongDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, Guangdong, People’s Republic of ChinaTel/Fax +86-18902268667Email zhongwei_gwcmc@163.comBackground: Hirschsprung disease (HSCR) is a congenital disease that arises from defective intestinal neural system. LncRNA HOTTIP is a critical gene in various diseases, including HSCR. No epidemiological studies have explored the correlation between lncRNA HOTTIP single nucleotide polymorphisms (SNPs) and HSCR risk. We here lead as a pioneer to explore whether SNPs in lncRNA HOTTIP impact the risk of HSCR and HSCR subtypes in an unrelated Chinese population.Methods: We used the TaqMan method to genotype rs3807598 C>G of the lncRNA HOTTIP gene using 1470 HSCR cases and 1473 healthy controls. Of them, 1441 cases and 1434 controls were successfully genotyped. We adopted odds ratios (ORs) and 95% confidence intervals (CIs) to quantify the relationship.Results: We got an unexpected outcome that lncRNA HOTTIP SNP rs3807598 C>G could not modify the risk of HSCR (CG vs. CC: adjusted OR=0.89, 95% CI=0.74– 1.07; GG vs. CC: adjusted OR=1.10, 95% CI=0.89– 1.37; GG/CG vs CC: adjusted OR=0.95, 95% CI=0.80– 1.13; and GG vs. CC/CG: adjusted OR=1.19, 95% CI=0.99– 1.43). What’s more, risk effect of lncRNA HOTTIP rs3807598 C>G is still not obvious in stratification analysis by HSCR subtype.Conclusion: Our studies did not provide statistical evidence of a correlation between lncRNA HOTTIP SNP rs3807598 C>G and susceptibility of HSCR in the Chinese population that is being studied. Further validation study with a larger sample size covering multi-ethnic groups is warranted.Keywords: Hirschsprung disease, HOTTIP, polymorphism, susceptibility, Chinese

Li Li, 1,* Zhenjian Zhuo, 2,* Zhen Yang, 1, 3,* Jinhong Zhu, 4 Xiaoli He, 1 Zhonghua Yang, 5 Jiao Zhang, 6 Yijuan Xin, 7 Jing He, 2 Tiesong Zhang 1 1Kunming Key Laboratory of Children’s Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Kunming Children’s Hospital, Kunming, Yunnan, 650228, People’s Republic of China; 2Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China; 3Department of Oncology, Kunming Children’s Hospital, Kunming 650228, Yunnan, People’s Republic of China; 4Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, People’s Republic of China; 5Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People’s Republic of China; 6Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China; 7Clinical Laboratory Medicine Center of PLA, Xijing Hospital, Air Force Medical University, Xi’an 710032, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiesong ZhangKunming Key Laboratory of Children’s Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Kunming Children’s Hospital, 288 Qianxing Road, Kunming 650228, Yunnan, People’s Republic of ChinaTel/Fax +86 – 8713169969Email zts68420@sina.comJing HeDepartment of Pediatric, Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, Guangdong, People’s Republic of ChinaTel/Fax +86 2038076560Email hejing198374@gmail.comBackground: Hepatoblastoma is a rare disease. Its etiology remains obscure. No epidemiological reports have assessed the relationship of High Mobility Group A2 (HMGA2) single nucleotide polymorphisms (SNPs) with hepatoblastoma risk. This case-control study leads as a pioneer to explore whether HMGA2 SNPs (rs6581658 A>G, rs8756 A>C, rs968697 T>C) could impact hepatoblastoma risk.Methods: We acquired samples from 275 hepatoblastoma cases and 1018 controls who visited one of five independent hospitals located in the different regions of China. The genotyping of HMGA2 SNPs was implemented using the PCR-based TaqMan method, and the risk estimates were quantified by odds ratios (ORs) and 95% confidence intervals (CIs).Results: In the main analysis, we identified that rs968697 T>C polymorphism was significantly related to hepatoblastoma risk in the additive model (adjusted OR=0.73, 95% CI=0.54– 0.98, P=0.035). Notably, participants carrying 2– 3 favorable genotypes had reduced hepatoblastoma risk (adjusted OR=0.71, 95% CI=0.52– 0.96, P=0.028) in contrast to those carrying 0– 1 favorable genotypes. Furthermore, stratification analysis revealed a significant correlation between rs968697 TC/CC and hepatoblastoma risk for males and clinical stage I+II. The existence of 2– 3 protective genotypes was correlated with decreased hepatoblastoma susceptibility in children ≥ 17 months old, males, and clinical stage I+II cases, when compared to 0– 1 protective genotype.Conclusion: To summarize, these results indicated that the HMGA2 gene SNPs exert a weak influence on hepatoblastoma susceptibility. Further validation of the current conclusion with a larger sample size covering multi-ethnic groups is warranted.Keywords: hepatoblastoma, HMGA2, polymorphism, susceptibility

The Millennium Eruption of Changbaishan Volcano is heralded as one of the largest explosive eruptions in the Late Holocene and produced huge quantities of tephra. The petrogeochemical method estimates that the Millennium Eruption emitted up to 45 Tg of sulfur into the atmosphere—more than in the Tambora eruption in 1815 CE, which caused "a year without a summer" across the Northern Hemisphere in 1816 CE. Despite such massive emissions, evidence for this eruption's climate impact in East Asia remains elusive. To explain this contradiction, this study used 67 high‐resolution tree‐ring‐width records from the Northern Hemisphere spanning the past two millennia, complemented by volcanic sensitivity experiments conducted with the Community Earth System Model. Results reveal a prevailing decreasing/negative trend in the proxy records during the potential eruption period, with 945 CE marking the most notable negative anomaly, suggesting that the Millennium Eruption likely occurred in 945 CE rather than 946 CE. Sensitivity experiments, corroborated by proxy records, demonstrate that the Millennium Eruption induced substantial negative temperature anomalies at middle and high latitudes, alongside an increase in Meiyu‐Baiu‐Changma precipitation in the middle and lower reaches of the Yangtze River and southwestern Japan and a decrease in precipitation in India, northern China, and the South China Sea in the first post‐eruption year. This study offers a novel perspective on the climate impact of the Millennium Eruption, reconciling previous discrepancies regarding its climate impact. Plain Language Summary: About a thousand years ago, the Changbaishan volcano erupted with incredible force, ranking as one of the largest historical eruptions in the past 2000 yrs. Despite its size, evidence for this eruption's climate impact in East Asia has remained elusive. We delved into this mystery by examining detailed high‐resolution proxy records and performing climate model simulations. Our findings suggest that the climate effects of the eruption may have been unexpectedly strong, with the Millennium Eruption potentially occurring in 945 CE that is earlier than previously thought. The Millennium Eruption triggered notable cooling at middle and high latitudes, increased Meiyu‐Baiu‐Changma precipitation in the middle and lower reaches of the Yangtze River and southwestern Japan, and reduced precipitation in India, northern China, and the South China Sea. This research helps us understand how large volcanic eruptions can interact with other natural factors to influence our climate. Key Points: Sulfur emissions of the Millennium Eruption estimated from a petrogeochemical method are inconsistent with the signal from ice‐core samplesA consistent negative response in the high‐resolution paleoclimate records suggests a significant climate impact of the Millennium EruptionThe eruption enhanced the Meiyu‐Baiu‐Changma precipitation while diminishing precipitation in India, northern China, and the South China Sea [ABSTRACT FROM AUTHOR]

Haixia Zhou,1,* Zhenjian Zhuo,2,* Shanshan Chen,1 Jie Zhao,1 Yixiao Mo,1 Jiao Zhang,3 Jing He,1,4 Jichen Ruan1 1Department of Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 2School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; 3Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; 4Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Introduction: Neuroblastoma is an embryonal tumor of the sympathetic nervous system. The MYCN oncogene is amplified in some neuroblastoma patients and correlated with poor prognosis. However, less is known regarding the relationship between MYCN gene single-nucleotide polymorphisms (SNPs) and neuroblastoma risk. Patients and methods: To investigate the contribution of MYCN gene polymorphisms to neuroblastoma risk, we performed a 3-center case–control study by genotyping 4 SNPs in the MYCN gene from 429 cases and 884 controls. Results: The results showed that only rs57961569 G>A was associated with neuroblastoma risk (GA vs GG: adjusted odds ratio =0.76, 95% confidence interval =0.60–0.98, P=0.033), while the other 3 SNPs were not (rs9653226 T>C, rs13034994 A>G, and rs60226897 G>A). Stratified analysis revealed that rs57961569 GG carriers were more likely to develop neuroblastoma in the following subgroups: children older than 18 months, tumor derived from the adrenal gland, and clinical stages III + IV. The increased neuroblastoma risk associated with the rs9653226 variant CC genotypes was more evident in the following subgroups: females, tumor derived from the adrenal gland, and clinical stages III + IV. The presence of 2–3 risk genotypes had a significant relationship with the following subgroups: tumor derived from the adrenal gland and clinical stages III + IV. Conclusion: This study demonstrates a weak impact of MYCN gene polymorphisms on neuroblastoma risk, which should be further validated. Keywords: neuroblastoma, susceptibility, MYCN, polymorphism

Jing He,1,* Zhen-Jian Zhuo,2,* Anqi Zhang,3,* Jinhong Zhu,4 Rui-Xi Hua,5 Wen-Qiong Xue,1 Shao-Dan Zhang,1 Jiang-Bo Zhang,1 Xi-Zhao Li,1 Wei-Hua Jia1 1State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China; 2Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; 3Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 4Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China; 5Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China *These authors contributed equally to this work Background: Potentially functional polymorphisms can modulate protein activities and host’s DNA repair capacity, thereby influencing cancer susceptibility. The association of the polymorphisms in the nucleotide excision repair core pathway genes and gastric cancer susceptibility remains largely unknown. Methods: Here, we systematically analyzed the associations between nine polymorphisms in four key genes (XPA, ERCC1, ERCC2, and ERCC4) in the nucleotide excision repair pathway and gastric cancer risk in a Chinese population including 1142 patients and 1173 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risk associations. Results: We observed that ERCC1 rs2298881 CA variant genotype was associated with an increased gastric cancer risk (CA vs. CC: adjusted OR [AOR]=1.33, 95% CI=1.09–1.62; dominant model: AOR=1.32, 95% CI=1.10–1.60). However, ERCC1 rs3212986 AA variant genotype was identified as a protective factor for gastric cancer (AA vs. CC: AOR=0.73, 95% CI=0.54–0.98; recessive model: AOR=0.72, 95% CI=0.54–0.96). Genotype-based mRNA expression analysis further indicated that the rs2298881 A allele was associated with decreased ERCC1 mRNA expression. Conclusion: In all, these results indicated that the ERCC1 polymorphisms may affect the risk of gastric cancer in the Chinese Han population. Keywords: gastric cancer, DNA repair, NER, polymorphism, susceptibility

Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1) via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MBSDF-1 destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair. Keywords: mesenchymal stem cell, ultrasound, microbubbles, homing, stromal cell-derived factor-1, diabetic nephropathy

Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department of Ultrasound, General Hospital of the Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g) > MTX alone (6.97±0.75 µg/g) > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (P

Background The incidence of infections among cancer patients is as high as 23.2–33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. Aim This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. Design This was a 5-year retrospective study on the antibiotic resistance of cancer patients. Methods In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. Findings Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. Conclusions The bacterial prevalence and antibiotic resistance rates of E. coli , K. pneumoniae , P. aeruginosa , A. baumannii , S. aureus and MRSA were significantly lower than the national average. [ABSTRACT FROM AUTHOR]