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Nana Long,1,2 Min Qiu,2 Youwei Zuo,1 Hongping Deng1 1Center for Biodiversity Conservation and Utilization, School of Life Sciences, Southwest University, Beibei, Chongqing, People’s Republic of China; 2School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Hongping Deng, Email denghp@swu.edu.cnPurpose: The purpose of this study was to evaluate the antibacterial activity and mechanism of linalool against Methicillin-resistant Staphylococcus aureus (MRSA).Methods: The determination of the antibacterial activity of linalool against clinically isolated MRSA strains was based on the minimum inhibitory concentration (MIC) and growth curve analysis. Finally, the inhibition mechanism of linalool was elucidated through metabolomic analysis and molecular docking.Results: Among the isolated strains, penicillin resistance was found to be the highest, while resistance to daptomycin/quinupristin-dalfopristin, linezolid, vancomycin, tetracycline, telithromycin, and levofloxacin was not observed. The MIC range of linalool was 211.24– 1.65 μg/mL, with MIC50 and MIC90 values of 13.2 μg/mL and 105.62 μg/mL, respectively. Metabolomic analysis revealed that linalool interferes with various substance metabolisms and energy metabolism in MRSA, with the glutathione pathway potentially being a key pathway affected by linalool. Molecular docking revealed that linalool exhibited good binding potential to the target glutathione.Conclusion: This study suggests that linalool could be developed as a drug or preservative to inhibit MRSA growth.Keywords: MRSA, linalool, antimicrobial resistance, metabolome, glutathione

Dong Zhang,1,2 Zeming Zhu,3 Zhangyou He,4 Siwei Duan,3 Qincheng Yi,4 Min Qiu,3 Xingzhen Dai,3 Guang Su,4 Kexin Li,1,2 Lin Xu,1,2 Donghou Liu,1,2 Yabin Wu,1,2 Yong Gao,3 Ruliu Li,3 Shaoju Guo1,2 1Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 2Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China; 4Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of ChinaCorrespondence: Ruliu Li, Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Tel +86-020-39357088, Email lrl@gzucm.edu.cn Shaoju Guo, Gastroenterology Department, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Shenzhen City, Guangdong Province, 518000, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.Methods: A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg− 1) and high-dose (10 g·kg− 1), and mesalazine (50 mg·kg− 1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.Results: Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.Conclusion: Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways. Keywords: ulcerative colitis, enema therapy, neutrophil extracellular traps, Chinese medicine, inflammation

Hengxin Chen,1,2,* Mingjin Qiu,1,2,* Hongxu Xu,1,2 Penghao Guo,1 Yaqin Peng1 1Department of Clinical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Clinical Laboratory, Nansha Hospital, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 511455, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaqin Peng, Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86 20 87618461, Email pyqdream@163.comBackground: Rhizomucor pusillus is one of the major pathogens in mucormycosis. Infection due to R. pusillus is rare and has a high mortality rate, especially disseminated mucormycosis infections. Rapid and accurate pathogen identification is important for the development of targeted antifungal therapies.Case Presentation: We presented a case of disseminated R. pusillus infection, identified through metagenomics next-generation sequencing (mNGS), in a 4-year-old patient with acute lymphoblastic leukemia. On days 22, 23, and 28, R. pusillus was detected in bronchoalveolar lavage fluid, blood, and hydrothorax, respectively, through mNGS. The patient developed lung, pleural, and blood disseminated lesions caused by R. pusillus infection. Subsequently, the patient was treated with antifungal therapy, including posaconazole, amphotericin B, and isacconazole, with supportive treatment. However, with the continuous deterioration of symptoms, the patient’s family decided to give up treatment. The patient eventually died of multiple-organ failure on day 34.Conclusion: mNGS facilitates prompt diagnosis of disseminated R. pusillus infections. The successful application of mNGS provided a new perspective for the clinician, underscoring the technique’s potential for rapid diagnostic etiology. mNGS has the capability to identify pathogens at the species level, which is a significant asset in guiding clinical medication decisions.Keywords: Rhizomucor pusillus, metagenomics next-generation sequencing, disseminated infection, diagnosis

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Min Qiu,1,2,&ast; Jinru Zou,2,&ast; Zheng Yang,3 Dan Yang,2 Rui Wang,1 Haie Guo1,4 1College of Veterinary Medicine, Inner Mongolia Agricultural University, Inner Mongolia, People’s Republic of China; 2College of Pharmacy, Baotou Medical College, Baotou, People’s Republic of China; 3The First Affiliated Hospital, Baotou Medical College, Baotou, People’s Republic of China; 4Agriculture, Animal Husbandry and Science and Technology Bureau of Liangcheng County, Ulanqab, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Wang; Haie Guo, Email wr2006@163.com; 153713887@qq.comAbstract: Exosomes belong to a subgroup of extracellular vesicles secreted by various cells and are involved in intercellular communication and material transfer. In recent years, exosomes have been used as drug delivery carriers because of their natural origin, high stability, low immunogenicity and high engineering ability. However, achieving targeted drug delivery with exosomes remains challenging. In this paper, a phage display technology was used to screen targeted peptides, and different surface modification strategies of targeted peptide exosomes were reviewed. In addition, the application of peptide-targeted exosomes in pulmonary diseases was also summarised.Keywords: exosome, targeted peptide modification, targeted delivery, lung

Danlei Song,1 Dan Cheng,2 Mengqin Qiu3 1College of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2The Third Clinical Medical College of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Women’s Hospital School of Medicine Zhejiang, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Danlei Song, Email 2210335116@qq.com

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

Jin G Choi,1,2 Pathik Amin,3 Alaina Tarantino,4 Mary Qiu3 1Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 2Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA; 3Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA; 4Ambulatory Pharmacy Services, University of Chicago, Chicago, IL, USACorrespondence: Mary Qiu, Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA, Tel +1 (773) 702-3937, Email mary.qiu@gmail.comPurpose: A major barrier to glaucoma medication adherence is the patient’s out-of-pocket costs. At the University of Chicago Medical Center (UCMC), the institutional pharmacy piloted a program to query out-of-pocket costs for each patient’s medication list based on their insurance coverage. This study aims to describe the impact of this collaboration between the glaucoma service and the outpatient pharmacy service.Methods: This study is a single institution, retrospective chart review of glaucoma patients with a formulary inquiry placed by a single glaucoma specialist between 4/1/2020 and 2/28/2022. Main outcome measures included medications before and after formulary inquiries, additional steps required to access the medications (ie, formulary exceptions, prior authorizations, tier exceptions), and out-of-pocket costs.Results: A total of 343 formulary inquiries, representing 568 individual medication inquiries, were conducted. Out of the 568 medication inquiries, only 78 could be filled for an affordable price without any additional steps. For 45 inquiries, additional steps were required for the medication to become covered at an affordable price. The remaining 445 inquires required additional steps with subsequent denial or prohibitive out-of-pocket costs.Conclusion: The UCMC workflow provided transparent out-of-pocket costs for patients to access glaucoma medications. This workflow may be cost-effective as it minimizes the burden on the overall system by reducing the number of patients who are unable to fill a prescription at the pharmacy due to issues with coverage or affordability. This model of physician-pharmacy collaboration can guide other institutions to implement similar workflows which directly mitigate costs and improve quality of care.Keywords: medication, access, cost

Peng Guo,1,&ast; Chi Huang,2,&ast; Qin Yang,1 Guofeng Zhong,1 Junbo Zhang,1 Mengyu Qiu,1 Rui Zeng,3 Kaijun Gou,3 Chen Zhang,1 Yan Qu1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Department of Pharmacy, Jiang’an Hospital of Traditional Chinese Medicine, Yibin, 644200, People’s Republic of China; 3Institute of Tibetan Plateau, Southwest Minzu University, Chengdu, 610225, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Qu; Chen Zhang, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com; chenzhang_1990@126.comAbstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA. Keywords: rheumatoid arthritis, dissolving microneedles, transdermal delivery system, degradability, biosafety

Liyu Yang,1,&ast; Long Zhou,1,&ast; Guanqi Wang,2 Min Qiu,1 Feng Liang,1 Changqing Jia,1 Weibing Xu,3 Qin Fu,1 Liqing Yang,1 Gen Ba1 1Department of Orthopedic, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Rehabilitation Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Spinal Surgery, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gen Ba, Department of Orthopedic, Shengjing Hospital of China Medical University, Sanhao Street 36, He Ping District, Shenyang, Liaoning Province, People’s Republic of China, 110004, Tel +86 18940259116, Email bagen1983@163.comObjective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases.Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97± 14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement.Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46± 46.09 min. The average follow-up time was 13.19± 1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84± 1.00 and 0.70± 0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46± 1.08 and 1.03± 0.64, respectively (P < 0.05). Significant differences existed between preoperative ODI scores (58.70± 11.22%) and the last follow-up ODI scores (9.24± 3.04%; P< 0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment.Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.Keywords: unilateral bi/multi-portal endoscopy, lumbar degenerative diseases, high-migrated disc herniation, bilateral spinal stenosis, ligamentum flavum, spinal endoscope

Jing Li,1,2,&ast; Liang Huang,1,&ast; Chao Ge,3,&ast; Xingwu Zhu,1 Maixuan Qiu,1 Chaopan Chen,3 Shaohua Wei,2 Yiqun Yan1 1Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 2Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of General Surgery, Ningbo Development Zone Hospital, Ningbo, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqun Yan, Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, No. 700 North Moyu Road, Shanghai, 201805, People’s Republic of China, Email ehbhyyq@163.com Shaohua Wei, Department of General Surgery, The Second Affiliated Hospital of Soochow University, No. 1055 Shanxiang Road, Suzhou, 215004, People’s Republic of China, Email shaohuawei2010@sina.comPurpose: Molecular targeted agents (MTAs) plus immune checkpoint inhibitors (ICIs) treatment for advanced hepatocellular carcinoma (HCC) has shown an exciting prospect. This study aimed to report the efficacy of the Simultaneous and Sequential use of them in a real-world practice.Patients and Methods: From April 2019 to December 2020, patients with advanced HCC in three Chinese medical centers receiving MTAs and ICIs as their initial systemic therapy were enrolled. Participants were classified into the Simultaneous group (treated with them simultaneously) and the Sequential group (treated with MTAs initially and added ICIs after tumor progression). Toxicity, tumor response, survival outcomes and prognostic factors were investigated.Results: One hundred and ten consecutive patients participated in the study (64 in the Simultaneous group and 46 in the Sequential group). A total of 93 (84.5%) patients experienced treatment-related adverse events (AEs), of which 55 (85.9%) in the Simultaneous group and 38 (82.6%) in the Sequential group (P=0.19). Grade 3/4 AEs were observed in 9 (8.2%) patients. Patients in the Simultaneous group achieved a higher objective response rate than those in the Sequential group (25.0% vs 4.3%, p=0.04). The median overall survival (OS) of the entire cohort was 14.8 [95% confidence interval (CI): 4.6– 25.5] months and the OS rates at 6 and 12 months were 80.6% and 60.9%, respectively. Patients in the Simultaneous group achieved better survival outcomes than those in the Sequential group, but without statistically significant differences. Child-Pugh 6 scores (HR: 2.97, 95% CI: 1.33– 6.61, P=0.008), tumor number ≤ 3 (HR: 0.18, 95% CI: 0.04– 0.78, P=0.022), extrahepatic metastasis (HR: 3.05, 95% CI: 1.35– 6.87, P=0.007) were independent prognostic factors for survival.Conclusion: The combined treatment of MTAs and ICIs shows good tumor response and survival outcomes with acceptable toxicity for advanced HCC in the real-world practice, in particular when they are applied simultaneously.Keywords: hepatocellular carcinoma, systemic therapy, molecular targeted agents, immune checkpoint inhibitors

Pinger Wang,1– 3,&ast; Jianbo Xu,1,&ast; Qi Sun,4,&ast; Qinwen Ge,2,3 Min Qiu,1 Kaiao Zou,2,3 Jun Ying,3,5 Wenhua Yuan,2,3 Jiali Chen,2,3 Qinghe Zeng,2,3 Qi Cui,1 Hongting Jin,2,3 Chunchun Zhang,1 Fanzhu Li1 1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Orthopedic Joint Surgery, Hangzhou Fuyang Hospital of TCM Orthopaedics and Traumatology, Hangzhou, People’s Republic of China; 5Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunchun Zhang, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel/Fax +86 571-86613684, Email 20081026@zcmu.edu.cn Fanzhu Li, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel/Fax +86 571-86613684, Email lifanzhu@zcmu.edu.cnBackground: Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated.Purpose: We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism.Methods: UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments.Results: In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG.Conclusion: E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.Graphical Abstract: Keywords: couplet medicines, UPLC-Q-TOF/MS, network pharmacology, cartilage degeneration, knee osteoarthritis, PPARG

Guo P, Huang C, Yang Q, et al. Int J Nanomedicine. 2023;18:7759-7784. The authors have advised the correspondence section on page 7759 is incorrect. The correct correspondence address is as follows. Correspondence: Yan Qu, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com The authors apologize for this error.

Mengying Qiu,1 Yijin Wu2 1School of English Studies, Sichuan International Studies University, Chongqing, 400031, People’s Republic of China; 2School of Translation Studies, Qufu Normal University, Rizhao, 276825, People’s Republic of ChinaCorrespondence: Yijin Wu, School of Translation Studies, Qufu Normal University, No. 5, Yantai Road, Donggang District, Rizhao, Shandong, 250100, People’s Republic of China, Tel/Fax +86 531 88377118, Email wuyijin9972@126.comObjective: This study aims to explore knowledge and perceptions of Chinese female college students towards HIV/AIDS.Design, Method, Participants and Setting: A purposive sampling method was used to recruit participants. Twenty female participants studying at a college located in Chongqing, Southwest China, were involved in the study. Semi-structured interviews were used to collect data. The face-to-face interview data were recorded and analyzed using the method of qualitative inductive content analysis.Results: Five themes were identified from the data of transcribed interviews: HIV transmission routes (sexual transmission; blood transmission; mother-to-child transmission), sources of HIV/AIDS knowledge (education; mass media), AIDS prevention measures (avoiding sexual activity; establishing sense of self-protection; avoiding blood contact), attitudes towards PLWHA (treating all PLWHA equally; showing sympathy for the innocent PLWHA; discriminating against the immoral PLWHA), and suggested solutions to combat AIDS (assistance provided by governments; what health professionals can contribute; mobilization of social power; university intervention).Conclusion: More efforts should be made to strengthen the HIV/AIDS education for female college students of non-medical majors in Southwest China. Accurate knowledge of HIV/AIDS and the right attitudes towards people living with HIV/AIDS (PLWHA) should be the foci of HIV/AIDS education for this population. In order to better cater future sex education in colleges to the requirements of female college students, educators and lawmakers may benefit from gaining a deeper grasp of their perspectives on HIV/AIDS.Keywords: HIV/AIDS, female college students, China, qualitative content analysis

Mya Abousy,1 Andy Schilling,1 Mary Qiu,2 Grant A Justin,3 Fatemeh Rajaii,1 Ximin Li,1 Fasika A Woreta1 1Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Ophthalmology, University of Chicago Medicine, Chicago, IL, USA; 3Department of Ophthalmology, Walter Reed National Military Medical Center, Bethesda, MD, USACorrespondence: Fasika A Woreta, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA, Email fworeta1@jhmi.eduPurpose: To describe ophthalmology resident experience with ophthalmic trauma cases in the U.S. Methods: We analyzed Accreditation Council for Graduate Medical Education (ACGME) case log data and de-identified case logs from US ophthalmology residency programs for residents graduating in 2018. Current Procedural Terminology (CPT) codes documented as “Globe Trauma” and trauma-related “Oculoplastic and Orbit” codes including lid lacerations and lateral canthotomies were analyzed.Results: 38 residency programs provided case logs (response rate: 32.2%). Residents performed an average of 7.24± 4.37 open globe repairs, 8.66± 6.94 lid laceration repairs, 0.49± 1.4 orbital fracture repairs, 1.22± 1.81 lateral canthotomies, and 0.28± 0.69 anterior chamber washouts as primary surgeon. On average, the most logged “Globe Trauma” procedure was open globe repair as primary surgeon. The more common trauma-related “Oculoplastic and Orbit” procedure was lid laceration repair as primary surgeon. 42.8% of residents did not log any lateral canthotomy procedures. Medium programs performed significantly more canthotomies than large programs (F(2166) = 6.35, p = 0.002), and large programs performed significantly more orbital fracture repairs than small and medium programs (F(2166) = 4.45, p = 0.013).Conclusion: Significant variation in globe trauma volume exists across programs. ACGME guidelines require a minimum of four globe trauma procedures for graduation, but procedures like anterior chamber paracentesis count towards this requirement. Open globe repairs, simple lid lacerations, and lateral canthotomies are basic skills every graduating resident should be competent in. Updating ACGME case log requirements for ophthalmic trauma and increasing opportunities for wet lab simulations may assist in ensuring graduating ophthalmology residents’ competency in performing these procedures.Keywords: globe trauma, ACGME, education, residency, surgical education

Xin Jiang, Yushuang Xu, Di Chen, Mengmeng Wang, Mengjun Qiu, Lina Xiong, Li Zhang, Honglu Yu, Zhifan Xiong Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhifan XiongDepartment of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel +86 13517281937Email xiongzhifan@126.comPurpose: Hepatocellular carcinoma (HCC) is a highly vascularized solid tumor characterized by neovascularization and vascular invasion. Angiogenesis plays an essential role in the occurrence and development of liver cancer. Our study aimed to investigate the prognostic value of angiogenesis-related genes in liver cancer.Patients and Methods: The transcriptome data and corresponding clinical information of patients with liver cancer were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. In the TCGA cohort, differential expression and prognostic analyses were used to screen angiogenesis-related candidate prognostic genes. We then used least absolute shrinkage and selection operator regression analysis to construct a prognostic signature using 10 angiogenesis-related prognostic genes. The reliability of the prognostic signature was assessed in the TCGA and ICGC cohorts. In addition, we comprehensively analyzed the correlation of the prognostic signature with the tumor microenvironment, chemotherapy drugs, and specific genes.Results: We identified 37 angiogenesis-related differentially expressed genes that were remarkably associated with prognosis. Ten of these genes were used to establish a survival and prognostic signature. This signature can distinguish between high-risk and low-risk groups and performs well in overall survival prediction, as demonstrated by internal and external validations. In addition, we observed that the high-risk group was remarkably associated with immune infiltration in the tumor microenvironment and had a different sensitivity to chemotherapeutic agents compared with the low-risk group. Moreover, the high-risk population was positively correlated with the expression of several special genes, such as immune checkpoint-related genes.Conclusion: Our results demonstrated that prognostic signatures based on angiogenesis-related genes are involved in the development of HCC and may provide new insights into accurate clinical decision-making and therapeutic evaluation of patients with HCC.Keywords: hepatocellular carcinoma, angiogenesis-related gene, signature, tumor microenvironment, immune infiltration, prognosis

Li Jiang,1,&ast; Wei Sun,2,&ast; Mi Zhang,3,&ast; Yaqing Wang,2 Yunfan Tian,2 Peng Li,2 Yan Lu,2 Tianhua Xu,2 Ming Qiu,2 Yun Yang,2 Xuemei Jia,3 Xiangqing Kong2 1Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Gynecological Tumor, Nanjing Maternity and Child Health Hospital, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangqing KongThe First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaTel +86 25 83718836Fax +86 25 83724440Email kongxq@njmu.edu.cnXuemei JiaThe Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Hospital), 123 Tianfeixiang, Mochou Road, Nanjing, Jiangsu Province, 210004, People’s Republic of ChinaTel/Fax +86 25 84460507Email xmjia@njmu.edu.cnAim: Several studies have demonstrated that increased omental adipose is a risk factor for obesity and metabolic syndrome. It remains unclear whether it is responsible for hypertension as an independent risk. This study was designed to assess the impact of omental adipose removal by surgery on blood pressure in cancer patients with or without hypertension.Methods and Results: In this prospective observational study, 133 patients with gastric or gynecological cancer were divided into 3 groups: non-hypertensive and omentum removed (NH&OR), hypertensive and omentum removed (H&OR), and hypertensive and omentum present (H&OP). Patients were followed up with systolic and diastolic blood pressure (SBP and DBP), changes in related body mass index and metabolic indices. The time points of the 2 follow-up visits were 1 month ± 7 days after the operation before the start of chemotherapy and the endpoint of 8 ± 1 month. Omental adipose tissues from both non-hypertensive and hypertensive patients in surgery were collected. We included 133 patients (84.2% female, 20.3% malignant gastric cancer and 79.7% malignant gynecological cancer, 78.2% omentum removal, 48.9% hypertensive), and all completed follow-up. H&OR group showed significant reductions in systolic and diastolic blood pressure compared with the baseline at 1-m (− 16.94/-10.50 mmHg, both P < 0.001) and 8-m end point (− 16.00/-5.50 mmHg, P < 0.001 and P = 0.004). Little reductions were observed with the body mass index of patients in 3 groups till the endpoint of study (H&OR group: 24.60 kg/m2 to 23.57 kg/m2, NH&OR group: 23.45 kg/m2 to 23.25 kg/m2, H&OP group: 25.74 kg/m2 to 25.24 kg/m2, all P > 0.05). No correlation was found between the baseline body mass index and 8-m change of systolic and diastolic blood pressure in omentum removed groups. In both groups, triglyceride levels were significantly increased at 4 ± 1 week after surgery (NH&OR 0.32 mmol/L, P = 0.006; H&OR 0.40 mmol/L, P = 0.010).Conclusion: Resection of omental adipose tissue represents an effective strategy for reducing systolic and diastolic blood pressure at 8 months in hypertensive patients, even in the non-obese hypertensive population.Keywords: hypertension, omentum adipose, mRNA microarray

Meiqing Qiu,1– 3 Ying Meng,3 Huijun Wang,3 Li Sun,3 Zhen Liu,3 Shifeng Kan,2 Tao Wang,2 Shu Zhang3 1Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Oncology, Zaozhuang Municipal Hospital, Zaozhuang, 277100, People’s Republic of China; 3Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Shu ZhangDepartment of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaTel/ Fax +86-531-67626836Email zhangshu@csco.org.cnObjective: Cancer is well known as the most important risk factor for the emergence of pulmonary embolism (PE). The incidence of incidental PE (IPE) has increased with widely use of multi-detector-row computed tomography (CT) technology. Simultaneously, more new cancer patients diagnosed concomitantly with IPE are found. No study has examined the presentation and prognosis of incidental pulmonary embolism (IPE) in gastric cancer patients. The aim of this study was to analyse prognostic factors in patients with advanced gastric cancer complicated with IPE.Patients and Methods: Ninety patients with histologically confirmed advanced gastric adenocarcinoma diagnosed with IPE were enrolled. Continuous variables were compared using Student’s t-test or the Mann–Whitney U-test if non-normally distributed. The Chi-squared test (or Fisher’s exact test where appropriate) was used to compare categorical variables. The Kaplan–Meier method and the Log rank test were used for survival analysis. Independent prognostic factors for survival were determined using a Cox proportional hazards model. A two-sided P-value < 0.05 was considered statistically significant.Results: Nineteen patients were diagnosed with IPE concomitantly with gastric cancer. Concurrence of gastric cancer and IPE, lack of anticoagulation therapy, and location of IPE were associated with survival. After adjusting for age and sex, the concurrence of gastric cancer and IPE, lack of anticoagulation, and central IPE independently influenced the survival of advanced gastric cancer patients with IPE. Subgroup analysis of patients with peripheral pulmonary embolisms confirmed that anticoagulant therapy provided a survival benefit.Conclusion: Concurrence of gastric cancer and IPE may be a prognostic factor for advanced gastric cancer patients with IPE.Keywords: incidental pulmonary embolism, gastric cancer, anticoagulation therapy

Lin Lin,1,2,&ast; Nana Long,1,2,&ast; Min Qiu,1,2 Yao Liu,1 Fenghui Sun,1,2 Min Dai1,2 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, 610500, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Dai; Fenghui SunSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of ChinaEmail daimin1015@cmc.edu.cn; sunfenghui@cmc.edu.cnIntroduction: Antibiotics wee widely used as feed additives in animal husbandry. With the increase of drug resistance of bacteria, there is an urgent need to find alternatives to antibiotics. Clinically, methicillin-resistant Staphylococcus aureus (MRSA) infections account for about 25% to 50% of Staphylococcus aureus infections worldwide. Similarly, it is also one of the pathogens that cause serious animal infections.Methods: We established a mouse model of systemic infection of MRSA to study the preventive effect of geraniol on MRSA and the immunomodulatory effect of geraniol. The mice in the experiment were injected with geraniol by intramuscular injection and were fed intraperitoneally with minimum lethal dose of MRSA. Then, the survival rate, inflammatory cytokines, oxidative stress factors in serum were measured. These values were used to estimate the bacterial load in different organs and to assess histopathological changes in the lungs, liver and kidneys.Results: The above-mentioned two ways of using geraniol could prevent MRSA infection in vivo in mice and showed a significant dose–response relationship. In other words, geraniol significantly decreased the concentrations of inflammatory cytokines and oxidative stress factors in MRSA-infected mice. At the same time, the level of glutathione peroxidase also increased in a dose–proportional relationship. In the group of mice treated with geraniol, their superoxide dismutase levels were significantly higher than those in the vancomycin. After treatment with geraniol, the burden of MRSA decreased. No obvious histopathological abnormalities were found in the liver and kidney of MRSA-infected mice. In addition, geraniol improved the inflammatory changes in the lungs.Conclusion: The results indicated that geraniol was a natural substance that could be used as an anti-inflammatory, antioxidant and antibacterial substance to protect mice from MRSA systemic infection. Generally, the research shows that as a natural medicine, geraniol has broad potential in the development and application of antibiotic substitutes.Keywords: MRSA, geraniol, antibacterial activity, inflammatory cytokines, in vivo

Li Sun,1,* Huijun Wang,1,* Zhen Liu,1 Ying Meng,1 Meiqing Qiu,2 Yafei Ju,1 Shu Zhang1 1Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Oncology, Zaozhuang Municipal Hospital, Zaozhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu ZhangDepartment of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaTel/Fax +86-0531-67626836Email zhangshu@csco.org.cnObjective: Many large-sample prospective randomized clinical trials investigating advanced gastric cancer (AGC) have confirmed the survival advantages of first-line, second-line, or third-line chemotherapy compared with their respective control groups. However, due to the ethical concerns of prospective clinical trials, it is impossible to conduct a randomized comparative study of patients who do not receive chemotherapy and those who receive a second-line or above chemotherapy. Few research reports have addressed the relationship between the number of chemotherapy lines and overall survival (OS) in patients with AGC. In the present study, we analyzed the impact of the number of chemotherapy lines on OS in AGC patients using real-world data.Patients and Methods: This study collected the medical records of patients with AGC diagnosed at Shandong Cancer Hospital from December 2007 to December 2017. According to the treatment received, AGC patients were divided into groups that did not receive chemotherapy, those who received only 1 line, 2 lines, or 3 lines and above. Kaplan–Meier analysis was used to assess patient survival.Results: A total of 596 AGC patients were included in this study. The following patients were enrolled: 0 lines (did not receive chemotherapy), 77 (12.9%); 1 line, 235 (39.4%) patients; 2 lines, 185 (31.1%) patients; and ≥ 3 lines 99 (16.6%) patients. OS was significantly correlated with the number of chemotherapy lines (P< 0.001), with a median OS from diagnosis of 3.3, 8.6, 15.6, and 21.0 months for patients receiving 0, 1, 2, ≥ 3 lines of chemotherapy, respectively.Conclusion: This study showed that the more chemotherapy lines AGC patients received, the longer the OS. This study not only confirmed the impact of chemotherapy lines on OS but it also supplements the results of prospective clinical trials that cannot be completed due to the ethical implications.Keywords: advanced gastric cancer, number of chemotherapy lines, overall survival, real world data

Fan Huang,1,* Mingwang Qiu,2,* Siyi Zhao,1,* Lin Dai,2 Yanpeng Xu,2 Yunying Yang,2 Liming Lu,2 Rusong Guo,1,3 Qiang Tian,1,3 Zhiyong Fan,1,3 Shan Wu1,3 1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, People’s Republic of China; 2Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, People’s Republic of China; 3Guangdong Province Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyong Fan; Shan Wu Guangdong Province Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; Guangdong Province Hospital of Chinese Medicine, Guangzhou 510120, Guangdong, People’s Republic of China Tel +86 188 9863 2932Email fzystrong@163.com; wushan6866@sina.comObjective: To evaluate systematic reviews (SRs) of acupuncture for low back pain (LBP) in terms of characteristics, reporting and methodological quality using a Veritas plot and to explore factors that may be associated with methodological quality and reporting quality.Study Design and Setting: We searched 8 electronic bibliographic databases to find all SRs, and we evaluated the SRs’ quality in 6 dimensions, including publication year, design type, homogeneity, risk of publication bias, methodological quality by Assessment of Multiple Systematic Reviews (AMSTAR) 2 and reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Excel 2010 and Adobe Illustrator CC were used to draw and optimize Veritas plots. Exploratory analysis was done using SPSS software version 23.0 to explore factors related to AMSTAR-2 and PRISMA scores. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence quality evaluation tool was used to grade all the outcome indicators in the included literature.Results: We included 19 SRs in the analysis. Literature quality rank scores ranged from 9.67 to 17.00, with an average score of 13.18 ± 2.35. The average score of AMSTAR-2 was 7.47, and the average score of PRISMA was 18.47. Overall, the main issues were research strategies, inclusion and exclusion criteria, publication bias, and registration in PROSPERO. The results of exploratory analysis showed that duplication of literature selected and appropriate tools to assess the risk of bias were related to the AMSTAR-2 score, and the summary of evidence was related to the PRISMA score. The GRADE quality evaluation results showed mainly low quality.Conclusion: The quality of SRs on acupuncture for low back pain should be improved, mainly by strengthening the methodological quality and reporting quality. The Veritas plot is an effective graphical evaluation method that is worth popularizing.Keywords: reporting quality, methodological quality, AMSTAR-2, low back pain, PRISMA, systematic review

Xiaofen Li,1 Hai Huang,1,2 Longyao Ran,3 Chao Fang,4 Yongyang Yu,4 Manxi Luo,5 Meng Qiu1 1Department of Abdominal Oncology, West China Hospital of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Oncology, People’s Hospital of Deyang City, Deyang, Sichuan, People’s Republic of China; 3Department of Medical Administration, West China Hospital of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Gastrointestinal Surgery, West China Hospital of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Faculty of Medicine, The University of New South Wales, Kensington, New South Wales, AustraliaCorrespondence: Meng QiuDepartment of Abdominal Oncology, West China Hospital of Medicine, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041, People’s Republic of ChinaTel + 86-28-85422589Fax + 86-28-85423609Email qiumeng33@hotmail.comBackground: Ovarian metastasis from colorectal cancer (CRC) is rare and lacks standard treatment. The benefit of metastatectomy remains to be elucidated. This study was conducted to assess the impact of metastatectomy on survival outcome and explore prognostic factors in ovarian metastatic CRC patients.Methods: Information of ovarian metastatic CRC patients between January 2008 and December 2017 were collected retrospectively from database of West China Hospital, Sichuan University. Kaplan–Meier method was used to estimate disease-specific survival (DSS) after diagnosis of ovarian metastasis, and multivariate Cox regression analysis was applied to identify prognostic factors.Results: Totally, 68 female patients from a cohort of 2170 cases were eligible. The median age at diagnosis was 46.5 years. The median DSS was 25.0 months (95% confidence interval (CI): 21.0– 29.0 months). Kaplan–Meier analysis and Log rank test showed that complete resection of ovarian metastases (median DSS: 33.0 months) could significantly prolong patients’ survival time, compared with palliative and no resection (median DSS: 20.0 months and 22.0 months, respectively), regardless of systemic chemotherapy (P< 0.05). Multivariate analysis demonstrated regional lymph nodes metastasis of primary tumor (hazard ratio (HR): 3.438, 95% CI: 1.094– 10.810, P=0.035), primary tumor resection (HR: 6.436, 95% CI: 1.770– 23.399, P=0.005), differentiation grade (HR: 0.272, 95% CI: 0.107– 0.693, P=0.006), complete resection of ovarian metastases (vs palliative resection: HR: 17.091, 95% CI: 3.040– 96.099, P=0.001; vs no resection: HR: 9.519, 95% CI: 1.581– 57.320, P=0.014), and systemic chemotherapy (HR: 3.059, 95% CI: 1.089– 8.595 P=0.034) were independent prognostic factors.Conclusion: Complete resection of ovarian metastases could independently predict favorable survival in ovarian metastatic CRC, while palliative resection could not improve patients’ prognosis compared with no resection.Keywords: ovarian metastasis, colorectal cancer, metastatectomy

Qianwen Xi, Yu Tao, Meiting Qiu, Yun Wang, Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to JiaoTong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yun Wang; Yanping KuangYanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to JiaoTong University School of Medicine, Shanghai, People’s Republic of ChinaEmail Kuangyp1506@sh9hospital.org; sammy20080228@icloud.comPurpose: To investigate whether progestin-primed ovarian stimulation (PPOS) can be an alternative as gonadotrophin-releasing hormone agonist (GnRHa) long protocol for infertile women with normal ovarian reserve during IVF/ICSI.Methods: A prospective randomized controlled trial (RCT) including 257 patients was conducted between 1 August 2017 to 1 January 2018. Computerized randomization was performed to assign participants into two treatment groups at a 1:1 ratio: PPOS (130 patients) or GnRHa long protocol (127 patients) followed by their first IVF/ICSI with fresh/frozen embryo transfer. The primary outcome was the number of oocytes retrieved. Patients with normal ovarian reserve undergoing their first IVF/ICSI procedure were included. The embryological and clinical outcomes were measured. Only the first embryo transfer cycle was followed-up.Results: Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in both groups. No significant difference was found in the number (mean ± SD) oocytes retrieved [11.8 ± 6.5 for PPOS vs 11.3 ± 5.6 for GnRHa long protocol] or viable embryos [4.5 ± 3.0 for PPOS vs 4.2 ± 2.9 for GnRHa long protocol] between the groups. No patient from either group experienced a premature LH surge during the whole process of ovarian stimulation. Besides, there was no moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation in PPOS group while three patients suffered it in the GnRHa long protocol group. There was no significant difference in the clinical pregnancy rate of the first embryos transfer cycle between the two groups.Conclusion: PPOS in combination with embryo cryopreservation as an ovarian stimulation regimen was as effective as GnRHa long protocol during controlled ovarian stimulation (COH) under different endocrinal mechanisms. It can also achieve comparable embryological and clinical outcomes while reducing the incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and HMG dosage. It can be an alternative of the treatments for infertile patients with normal ovarian reserve undergoing IVF as well as traditional protocols.Trial Registration Number: ChiCTR-INR-17012089.Trial Registration Date: Chictr.org.cn: 23 July 2017.Date of First Patient’s Enrollment: 1 August 2017.Keywords: medroxyprogesterone acetate, progestin-primed ovarian stimulation, premature LH surge, ovarian stimulation, ovarian hyperstimulation syndrome