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Qian Zeng,1 Lu Liu,1 Ying Chen,1 Daohong Chen,1 Ziyang Zhou,1 Wenjiao Hu,1 Siyao Gong,1 Bin He,1 Wenchuan Qi,1,2 Chao Wang,1,3 Zuoqin Yang,4 Shuguang Yu,1,2 Ling Zhao1,2 1Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Key Laboratory of Acupuncture for Senile Disease, Chengdu University of Traditional Chinese Medicine, Ministry of Education, Chengdu, People’s Republic of China; 3Sub-health Management Center, Sichuan Integrative Medicine Hospital, Chengdu, People’s Republic of China; 4Department of Acupuncture and Tuina, Chengdu Pidu District Hospital of Traditional Chinese Medicine, Sichuan, People’s Republic of ChinaCorrespondence: Ling Zhao, Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cnBackground: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD.Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs.Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were “critically low”. Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1.Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.Keywords: acupuncture, COPD, systematic reviews, overview

Shengping Gong,1 Cong Shi2 1Cancer Radiotherapy and Chemotherapy Center, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Laboratory of Stem Cell Transplantation, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of ChinaCorrespondence: Cong Shi, Email shicong5103@sina.comBackground: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear.Methods: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models.Results: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (< 10 g/dl, P = 0.029), higher BM blast (> 5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS.Conclusion: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.Keywords: myelodysplastic syndrome, lymphocyte subsets, prognostic, IPSS-R, natural killer cell

Shuwei Gong,1,&ast; Shuang Lang,2,&ast; Yan Wang,3,&ast; Xiongfeng Li,1,&ast; Aixian Tian,3 Jianxiong Ma,3 Xinlong Ma3 1Department of Orthopedics, Huzhou Central Hospital, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, People’s Republic of China; 2Department of Traditional Chinese Medicine, Huzhou Central Hospital, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, People’s Republic of China; 3Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering, Orthopedic Research Institute, Tianjin Hospital, Tianjin, 300050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxiong Ma; Xinlong Ma, Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering, Orthopedic Research Institute, Tianjin Hospital, 155 Munan Road, Heping District, Tianjin, 300050, People’s Republic of China, Email mjxtianjin@foxmail.com; maxinlong8686@126.comBackground: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research.Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo.Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤ 120 μg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent.Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect. Keywords: pH-sensitive gated nano-drug delivery system, mesoporous silica nanoparticles, naringin, chitosan, osteoclast

Kang Wang,1,&ast; Zihui Yang,1,&ast; Boyu Zhang,1,&ast; Song Gong,2 Yiping Wu1 1Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Division of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Song Gong, Division of Endocrinology, Tongji Hospital, Tongji Medical College, Wuhan, Hubei, People’s Republic of China, Email gongsong@tjh.tjmu.edu.cn Yiping Wu, Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Wuhan, Hubei, People’s Republic of China, Email tongjiplastic@163.comAbstract: Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles in facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance diabetic wound healing. We emphasize the biologically active molecules released by these exosomes and their involvement in signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, and other pertinent processes. Additionally, the clinical application prospects of the reported ADSC-eoxs are also deliberated. A thorough understanding of these molecular mechanisms and potential applications is anticipated to furnish a theoretical groundwork for combating diabetic wound healing.Keywords: diabetes, wound healing, ADSC-exos, tissue regeneration, skin cells, inflammation

Ziwei Huang,1 Shanli Zhang,1 Zehui Qin,1 Gaoxiang Ai,1 Minhua Li,1 Shiting Gong,1 Yuhong Liu,1 Huifang Zeng,2 Jiannan Chen,1 Ziren Su,1 Zhengquan Lai3 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Zhengquan Lai, Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China, Email cruise0303@163.com Ziren Su, School of pharmaceutical sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China, Email suziren@gzucm.edu.cnPropose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration–effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-β-cyclodextrin (HP-β-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work.Methods: OBB-HP-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-β-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-β-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers.Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-β-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-β-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-β-CD SDDS (10.882 μg/mL&ast;h) was significantly higher than that of the raw OBB counterpart (0.701 μg/mL&ast;h). The oral relative bioavailability of OBB-HP-β-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5– 10 times higher than that of OBB raw material.Conclusion: Based on our findings above, OBB-HP-β-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB. Keywords: oxyberberine, cyclodextrin, supersaturated drug delivery systems, pharmacokinetics, hyperuricemia

Nan Mei,1,&ast; Sha Gong,1,&ast; Lizhao Wang,2 Lu Wang,1 Jincheng Wang,1 Jianpeng Li,3 Yingying Bao,4 Huanming Zhang,1 Huaiyu Wang1 1Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Breast Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 4Institute of Gene and Cell Therapy, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaiyu Wang, Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shannxi, 710061, People’s Republic of China, Email why@xjtufh.edu.cn; whymed@126.comBackground: Multiple myeloma (MM), an incurable plasma cell malignancy. The significance of the relationship between natural killer (NK) cell-related genes and clinical factors in MM remains unclear.Methods: Initially, we extracted NK cell-related genes from peripheral blood mononuclear cells (PBMC) of healthy donors and MM samples by employing single-cell transcriptome data analysis in TISCH2. Subsequently, we screened NK cell-related genes with prognostic significance through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. Following the initial analyses, we developed potential subtypes and prognostic models for MM using consensus clustering and lasso regression analysis. Additionally, we conducted a correlation analysis to explore the relationship between clinical features and risk scores. Finally, we constructed a weighted gene co-expression network analysis (WGCNA) and identified differentially expressed genes (DEGs) within the MM cohort.Results: We discovered that 153 NK cell-related genes were significantly associated with the prognosisof MM patients (P < 0.05). Patients in NK cluster A exhibited poorer survival outcomes compared to those in cluster B. Furthermore, our NK cell-related genes risk model revealed that patients with a high risk score had significantly worse prognoses (P < 0.05). Patients with a high risk score were more likely to exhibit adverse clinical markers. Additionally, the nomogram based on NK cell-related genes demonstrated strong prognostic performance. The enrichment analysis indicated that immune-related pathways were significantly correlated with both the NK subtypes and the NK cell-related genes risk model. Ultimately, through the combined use of WGCNA and DEGs analysis, and by employing Venn diagrams, we determined that ITM2C is an independent prognostic marker for MM patients.Conclusion: In this study, we developed a novel model based on NK cell-related genes to stratify the prognosis of MM patients. Notably, higher expression levels of ITM2C were associated with more favorable survival outcomes in these patients.Keywords: multiple myeloma, NK cell-related genes, NK subtypes, prognostic model, ITM2C

Lu Liu,1,&ast; Zili Tang,1,&ast; Qian Zeng,1,&ast; Wenchuan Qi,1 Ziyang Zhou,1 Daohong Chen,1 Dingjun Cai,1– 3 Ying Chen,1 Shiqi Sun,1 Siyao Gong,1 Bin He,1 Shuguang Yu,1– 3 Ling Zhao1– 3 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu City, Sichuan Province, People’s Republic of China; 2Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 3Key Laboratory of Acupuncture for Senile Disease (Chengdu University of Traditional Chinese Medicine), Ministry of Education, Chengdu City, Sichuan Province, China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao; Shuguang Yu, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cn; ysg28588@126.comBackground: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking.Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively.Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module–trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB.Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.Keywords: chronic obstructive pulmonary disease, electroacupuncture, intensity, transcriptome profiling, weighted gene co-expression network analysis

Xiaoling Zhang,1,2 Jing Tao,1,2 Song Gong,1,2 Xuefeng Yu,1,2 Shiying Shao1,2 1Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Shiying Shao, Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Jiefang Road 1095, Wuhan, Hubei Province, 430030, People’s Republic of China, Tel +86-13627144576, Fax +86-27-83662883, Email shaoshiyingtj@163.comBackground: Diabetic lower extremity ulcer, including diabetic foot ulcer (DFU) and leg ulcer, is one of the refractory complications of diabetes, the treatment of which is challenging, expensive, and lengthy. Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor (rhGM-CSF) is an immunomodulatory cytokine that has been mainly applied in the treatment of hematological diseases. Clinical evidence regarding GM-CSF in the treatment of diabetic lower extremity ulcers is limited. This study is the first case series that investigates the repurpose effects of rhGM-CSF on diabetic ulcer healing in real clinical practice.Methods: Nine patients diagnosed with diabetes and refractory lower extremity ulcer (ulcer duration ≥ 2 weeks) were included from September 2021 to February 2023 in the Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Patients with Wagner grade ≥ 4 and SINDAD ≥ 5 were excluded. The included subjects were treated with rhGM-CSF plus standard of care (SOC) including glycemic control, foot care education, debridement of necrotic tissues, topical wound dressings, offloading, and infection control when necessary. The observation endpoint was complete epithelialization. Their clinical manifestations, laboratory tests, and therapeutic effects were extracted and analyzed.Results: The case series included 9 cases aged from 29 to 80 years and all the patients were male. Seven of 9 patients presented neuropathic ulcer. Only one case showed non-infected ulcer from tissue samples and one case presented ankle brachial index (ABI) < 0.9. It was observed that the ulcer areas among these 9 patients gradually declined throughout the whole treatment period with the average healing velocity 0.32 ± 013 cm2/day and the mean time to complete healing 16.0 ± 3.7 days. The relative area (percentage of initial ulcer area) decreased to 66.7 ± 13.0% on average after the first treatment. Ulcers in all the 9 patients achieved complete epithelialization after 4– 8 times treatments.Conclusion: The case series suggests rhGM-CSF as a promising therapeutic strategy for the treatment of diabetic ulceration. More robust data from randomized controlled trials are required to further evaluate its clinical efficacy.Keywords: recombinant human granulocyte/macrophage colony-stimulating factor, diabetic lower extremity ulcer, diabetic foot ulcer

Chengzhen Liu,1,2 Shen Tu,3 Shikang Gong,1 Jinliang Guan,1 Zifu Shi,1 Yi Chen2 1Department of Psychology, Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of China; 2School of Humanities and Management Science, Southwest Medical University, Luzhou, 626000, People’s Republic of China; 3Department of Psychology, School of Public Administration, Guizhou University of Finance and Economics, Guiyang, 550025, People’s Republic of ChinaCorrespondence: Zifu Shi; Yi Chen, Email shizf@hunnu.edu.cn; chenyi@swmu.edu.cnObjective: This study innovatively investigated the potential selection bias involved in processing multiple subliminal stimuli during creative problem-solving (CPS). It addresses the existing gap in specialized research on how the handling of multiple unconscious stimuli influences higher-order cognitive processes, particularly creativity.Methods: The study utilized a masked priming paradigm and a remote association task (RAT). Two experiments were conducted. Experiment 1 presented two stimuli simultaneously, with one being the correct answer, to examine whether there was a bias in the location of subliminal stimuli. In Experiment 2, two stimuli were presented sequentially, with one serving as the answer, to investigate whether there was a temporal bias in unconscious processing.Results: Our findings revealed that when solving easy RATs, subliminal stimuli presented on the left side had a negative priming effect compared to the right side. The results revealed that unconscious processing of subliminal stimuli enhanced performance on difficult CPS. Additionally, a temporal bias was observed, with more recent subliminal stimuli having a stronger effect than earlier stimuli.Conclusion: Unconscious processing can improve CPS, especially for difficult tasks, and there is a bias towards processing stimuli on the left and more recently presented stimuli. These findings contribute to our understanding of unconscious processing, particularly the processing of multiple subliminal stimuli in CPS, and provide insights into the biases that exist in unconscious processing.Keywords: unconscious priming, creative problem solving, remote association test, unconscious processing bias, multiple unconscious influences

Gao Y, Gong S, Zhou W, Li X, Gan X. Neuropsychiatr Dis Treat. 2023;19:1003-1016. Following a review of the Wake Letter to the Editor published July 25, 2023, the authors have published this corrigendum. On page 1003, the title should be “Prevalence and Risk Factors of Subsyndromal Delirium in the Intensive Care Units: A Prospective Case-Control Study”. On page 1003, In the objective part of the abstract, “The aim of this study was to explore the prevalence and risk factors for SSD among adult patients admitted to the ICU of XXX hospital in Southwest China” should be “The aim of this study was to explore the prevalence and risk factors for SSD among adult patients admitted to the ICU of the Second Affiliated Hospital in Chongqing, Southwest China”. In the methods section of the abstract in the first sentence, “in XXX hospital” should have been deleted. In the results section of the abstract, 2nd sentence, “MMSE score” should have been “low MMSE score”. On page 1004, Introduction section, 2nd and 3rd paragraph reference to “subdelirium syndrome” and “subdelirium” should be “SSD” in each case. In the 4th paragraph “The incidence of SSD in post-operative cardiac patients is 34%, the incidence of delirium in this group is 12%, and delirium occurs in approximately 2% of SSD patients” should be “In post-operative cardiac patients, SSD is reported at 34%, delirium is reported at 12%, and delirium occurs in approximately 2% of SSD patients”. In the 4th and 5th paragraphs “incidence” should have been “prevalence”. On page 1004, Materials and Methods section, Study Design subsection “A single-center, prospective cohort study design was used in the present study” should have been “A single-center, prospective case-control study design was used in the present study. This study was informed by the STROBE guidelines for reporting observational epidemiological studies”. On page 1005, Measurements section, 1st paragraph, 3rd sentence “Patients who exhibited fluctuations in condition, changes in cognitive level or level of consciousness, or were under analgesic and sedative medication, were assessed and recorded at all times until the patient was transferred from the ICU, or delirium or death occurred” should have been “Patients were evaluated at any time they experienced fluctuations in condition, changes in cognitive level or level of consciousness, or received analgesic and sedative medications. The endpoint of the assessment is the transfer of the patient out of the ICU, or the development of delirium or death.” 2nd paragraph, 3rd sentence “Patients with a score between 1 and 3 for the items are diagnosed with subclinical delirium” should have been “Patients with a score between 1 and 3 for the items are diagnosed with SSD”. On page 1005, Data Analysis section, 1st paragraph, 2nd sentence “A previous study reported that the incidence of SSD is approximately 40%.17” should have been “A previous study reported that the prevalence of SSD is approximately 40%.17”. 3rd sentence “SDD incidence” should have been “SSD incidence”. On page 1005, Data Analysis section, last paragraph, 2nd to last sentence “The patient’s last assessment before SSD occurred was used for case group and the highest total score was used for the control group to conduct univariate and regression analyses” should have been “Univariate regression analyses were performed using the patient’s first ICU admission for the control group and the highest total score for the case group”. On page 1008, Table 1, 1st column, “Constraint” should have been “Restraint”. On page 1010, Results section, Risk Factors subsection, the first paragraph should be “The difference between the two groups was statistically significant when comparing age, hypertension, history of mental illness, auxiliary ventilation, hemodialysis, activity status, number of medication ≥5, MMSE, body temperature ≥37.5°C, ADL, APACHEII and magnesium (P

Cong Shi,1,&ast; Shengping Gong,2,&ast; An Wu,3 Tingting Niu,1 Ningning Wu,1 Yi Zhang,1 Guifang Ouyang,3 Qitian Mu1 1Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Cancer Radiotherapy and Chemotherapy Center, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 3Hematology Department, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Ouyang; Qitian Mu, Email nbhematology@163.com; muqitian@163.comBackground: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS.Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models.Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188).Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.Keywords: myelodysplastic syndrome, IPSS-R, prognostic, overall survival, fibrinogen

Bo Wang,1,&ast; Song Gong,2,&ast; Lizhi Han,2 Wenkai Shao,2 Zilin Li,2 Jiawei Xu,2 Xiao Lv,2 Baojun Xiao,2 Yong Feng2 1Department of Rehabilitation, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baojun Xiao; Yong Feng, Email drxiao999@sohu.com; fengyong@hust.edu.cnBackground: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation.Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs.Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator.Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.Keywords: HDAC9, hBMSCs, osteogenesis, MAPK signaling pathway

Qingsong Tao,1,&ast; Xin Li,2,&ast; Ting Zhu,1 Xiaoqin Ge,1 Shengping Gong,1 Jianxin Guo,1 Ruishuang Ma1,3 1Department of Radiotherapy and Chemotherapy, Ningbo First Hospital, Ningbo, People’s Republic of China; 2Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 3Central Laboratory of the Medical Research Center, Ningbo First Hospital, Ningbo, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxin Guo; Ruishuang Ma, Department of Radiotherapy and Chemotherapy, Ningbo First Hospital, Ningbo, People’s Republic of China, Email nbdyyygjx@163.com; xiaomisara@163.comPurpose: Lactate, a marker of tumor metabolic reprogramming, maintains the acidic microenvironment and also affects the metabolism and function of immune cells. SLC16A3 is responsible for the extracellular transport of lactate, which is a key component of glycolysis. However, the role of SLC16A3 in immune infiltration and immunosuppression of lung cancer is largely unknown. Our study explored the therapeutic and prognostic value of SLC16A3 in predicting immune infiltration and immune checkpoint efficacy of lung cancer.Methods: SLC16A3 expression was evaluated with TCGA database. Kaplan–Meier analysis was performed for survival rates. GO and KEEG enrichment was conducted to determine predictive signaling pathways. We utilized TIMER and CIBERSORT to analyze the correlation between SLC16A3 and immunocyte infiltration as well as immune checkpoint. Interleukin and HIF-1a expression was measured with ELISA kit and flow cytometry separately.Results: In comparison with normal tissues, SLC16A3 expression was significantly upregulated in both lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC), which was closely related to poor prognosis. GO analysis indicated that SLC16A3 involved in different signal pathways in LUAD and LUSC and linked to HIF-1 signaling in LUAD. High SLC16A3 was correlated with immunosuppressive cells (Treg, Th2 and iDC), immune checkpoint (PD1, PD-L1, PVR, Tim-3, ITGAM) and immunosuppressive factors (foxp3, TGF-β) in LUAD not LUSC. Furthermore, SLC16A3 was identified to tightly interact with IL-8 which may induce microenvironment immune tolerance. Based on the clinical prediction, we performed experiments with LUAD A549 cells and showed reduced IL-8 and HIF-1a when treated with SLC16A3 knockdown. HIF-1a stimulation by dimethyloxalylglycine (DMOG) could restore IL-8 secretion in SLC16A3 downregulated cells.Conclusion: Taken together, our results suggest that SLC16A3 contributes to a worse prognosis in lung cancer and may play an important role in immune microenvironment and evasion through HIF-1a-IL8 axis, which could be a novel therapeutic target for immunotherapy in lung cancer.Keywords: SLC16A3 (MCT4), IL-8, lung cancer, immune evasion, bioinformatics analysis

OBJECTIVE: Ferroptosis of neurons is a significant cause of brain injury following intracerebral hemorrhage (ICH). As an iron-containing compound in hemoglobin, heme contributes to nerve injury post-ICH. Melatonin has been shown to mitigate the effects of ICH, yet its specific functions remain largely elusive. In this study, we aimed to explore the roles and mechanisms of melatonin in heme-induced ferroptosis subsequent to ICH. MATERIALS AND METHODS: C57BL/6 mice were intracranially injected with heme and then treated with melatonin. Behavior tests [modified neurological severity score (mNSS), forelimb placing, and corner turn tests], H&E staining, Nissl staining, and Prussian blue staining were used to evaluate mouse brain tissue injury. In vitro, HT-22 cells were stimulated with heme and cell viability was determined by crystal violet staining. The iron contents were determined in heme-treated brains and cells, and the levels of 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA) were assessed by ELISA. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Immunoblotting was used to analyze the protein expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Finally, small interfering RNA (siRNA) was used to knock down Nrf2 in HT-22 cells. RESULTS: Melatonin treatment alleviated heme-induced injuries to neural function, as indicated by improved behavior in the mice. Moreover, melatonin decreased cell death and iron concentrations, increased MDA and 4-HNE levels, and reversed the decreases in GPX4, SLC7A11, Nrf2, and HO-1 induced by heme in vitro and in vivo. These results indicated that melatonin could improve the ferroptosis induced by heme. In addition, we found that Nrf2 knockdown attenuated the therapeutic effect of melatonin on neuronal ferroptosis induced by heme. CONCLUSIONS: In general, melatonin alleviates heme-induced ferroptosis by activating the Nrf2/HO-1 pathway, which implies that melatonin is a promising treatment for ferroptosis in ICH. [ABSTRACT FROM AUTHOR]

Shengyan Huang,1,&ast; Xirong Tan,1,&ast; Ping Feng,1,2,&ast; Sha Gong,1 Qingmei He,1 Xunhua Zhu,1 Na Liu,1 Yingqing Li1 1State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy; Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingqing Li; Na Liu Tel +86-20-87343255; +86-20-87342370Fax +86-20-87342370Email liyingq1@sysucc.org.cn; liun1@sysucc.org.cnObjective: Metabolic syndrome has been identified as a prognostic predictor in multiple cancers. This study aimed to evaluate the impact of metabolic syndrome on the clinical outcome of patients with nasopharyngeal carcinoma (NPC) and its mechanism.Methods: A cohort of 2003 NPC patients with a median follow-up time of 96.3 months (range: 4.1– 120.0 months) were enrolled in this analysis. Kaplan–Meier curves and the Log rank test were used to determine the differences in progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Univariate and multivariable analyses were used to identify independent prognostic predictors. Untargeted metabolomics (LC-HRMS) was used to detect the serum metabolic profiles of 10 well-matched patients with or without metabolic syndrome. Differential metabolite-based enrichment analysis and pathway analysis were performed to identify the potential mechanism of metabolic syndrome in NPC.Results: A total of 171/2003 (8.5%) patients were diagnosed with metabolic syndrome, and these patients tended to be male (P < 0.001) and older (P = 0.003). Patients with metabolic syndrome had poorer PFS (P = 0.011), CSS (P = 0.003) and OS (P = 0.001) than those without metabolic syndrome. Univariate and multivariable analyses showed that metabolic syndrome was a statistically significant and independent predictor for PFS (HR: 1.34, 95% CI: 1.03– 1.75, P = 0.032), CSS (HR: 1.53, 95% CI: 1.12– 2.08, P = 0.008), and OS (HR: 1.50, 95% CI: 1.13– 2.00, P = 0.006). The serum metabolic profile of patients with metabolic syndrome was distinct from that of patients without metabolic syndrome. A total of 319 differential metabolites [log2(FC)> 1 or log2 (FC)

Susan Gong,1 Lakshay Khosla,1 Fred Gong,1 Nikhil Kasarla,1 Karel Everaert,2 Jeffrey Weiss,1 Abdo Kabarriti1 1Department of Urology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA; 2Department of Uro-Gynecology, Ghent University Hospital, Ghent, BelgiumCorrespondence: Susan GongDepartment of Urology, State University of New York Downstate Health Sciences University, 450 Clarkson Ave., Brooklyn, NY, 11203, USATel +1 845-891-6642Email Susan.Gong@downstate.eduPurpose: Current literature has suggested a relationship between nocturnal enuresis (NE) in childhood and the development of nocturia later in life as both disorders have similar underlying etiologies, comorbidities, and treatments. The objective was to synthesize the available evidence on the association between childhood NE and later presentation of nocturia.Methods: PubMed, CINAHL, Scopus, and Google Scholar were searched for peer-reviewed studies published between January 1980 and April 2021. Case–control and cohort studies that reported on childhood NE and current nocturia were included. The PRISMA protocol was followed (PROSPERO ID: CRD42021256255). A random-effects model was applied to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). Risk of bias was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria and with a funnel plot.Results: Of the 278 articles identified, 8 studies met inclusion criteria. The 6 case–control and 2 prospective cohort studies resulted in a total sample size of 26,070 participants. In a random-effect pooled analysis, childhood NE was significantly associated with the development of nocturia (OR: 1.75, 95% CI: 1.11– 2.40). Significant heterogeneity (I2 = 92.7%, p < 0.01) was identified among the included studies, which was reflected in an asymmetrical funnel plot. NE and nocturia have similar underlying etiologies of hormonal abnormalities, sleep disorders, physiological disorders, and psychological disorders.Conclusion: The history of childhood NE is significantly associated with nocturia later in life. The data in this meta-analysis support this transition and identify potential similarities between the two disorders. The sparse number of articles relevant to this topic is a strong indicator of the need for more work on this transition from childhood to maturity. More studies are warranted to further explore the association between NE and nocturia.Keywords: LUTS, pediatric urology, incontinence, nocturnal polyuria

Meihong Sheng,1 Juan Ji,1 Chenying Zhang,1 Zirui Zhang,1 Shenchu Gong,1 Yihua Lu2 1Department of Radiology, Affiliated Hospital 2 of Nantong University, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China; 2Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, 226019, Jiangsu, People’s Republic of ChinaCorrespondence: Shenchu Gong Email gongshenchu@msn.comBackground: Full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) are used separately or in combination to identify small breast lesions. The dose of the examination depends on the density of the breast and the imaging (FFDM or DBT) performed. We have performed a retrospective review of FFDM and DBT in women with denser breasts in order to demonstrate how varying the combination of FFDM and DBT in CC and MLO views affects lesion detection and the average gland dose.Methods: Eighty-one patients with dense breast received both full-field digital mammography (FFDM) and DBT bilateral screening. The recorded data included the display rates for small lesions or other positive lesions, the type of breast gland, the average gland dose (AGD), and the compression thickness of different collection methods. ANOVA was used to compare the AGD among different collection combinations, and t-test was used to perform pairwise comparison between groups with the same gland type. The relationship between AGD and compression thickness was analyzed by Pearson linear correlation, and the lesion display rates were compared using Chi-square test.Results: We found that AGDs were significantly different among the 6 collection methods (F = 119.06, p< 0.01), but were not obviously different between groups with the same gland type (F = 0.848, p> 0.05). The types of dense glands were correlated with compression thickness, and the thickness was moderately to strongly correlated with AGD (r=0.596– 0.736). The combination of single-view DBT(CC-DBT) and FFDM showed significantly higher mass display rates than the two-view FFDM (p< 0.05), while the display rates for other positive lesions were similar (p> 0.05).Conclusion: Our study showed that in opportunistic screening of patients with small breast masses that can be easily detected by ultrasound, MLO-FFDM+CC-DBT or CC-FFDM+MLO-DBT combinations can better balance the individual average gland dose and detection accuracy. The study result cannot be applied to the detection of non-mass lesions as the numbers are too small.Keywords: breast, breast tomography, screening, digital mammography, average gland dose

Plankton are the foundation of the food chain in aquatic environments, and changes in phytoplankton community structure and function could pose risks to human health through their impacts on pollutant activity. We studied the correlation of plankton community and functional groups to the environmental factors in the Fuhe River, China. Water quality was evaluated based on Qr-index of phytoplankton diversity and functional group biomass. From September 2020 to August 2021, a total of 304 phytoplankton and 158 zooplankton species were collected. The phytoplankton were divided into 30 functional groups, whereas zooplankton were divided into nine functional groups. Phytoplankton functional groups were mainly composed of groups H1, MP, and W1. Among them, functional group MP had the greatest biomass, accounting for 34.37% of the phytoplankton biomass, followed by H1 (10.61%), and W1 (10.10%). The zooplankton functional groups mainly consisted of RF, RC, and SCF functional groups. The functional group RC accounted for 48.81% of the total zooplankton biomass, followed by RF (20.46%), and SCF (19.65%). The major environmental factors influencing phytoplankton functional groups were water temperature (WT), dissolved oxygen (DO), oxidationreduction potential (ORP), and transparency (TS), whereas the major environmental factors influencing zooplankton functional groups were WT, pH, and DO. Overall, water quality of Fuhe River Basin was good, being slightly polluted or pollution-free. [ABSTRACT FROM AUTHOR]

Shiyi Gong,1 Hao Hu,2 Kun Zhao,2 Ting Yang1 1Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Disease; Institute of Respiratory Medicine, Chinese Academy of Medical Science; Peking University Health Science Center, Beijing, People’s Republic of China; 2China National Health Development Research Center, National Health Commission of the People’s Republic of China, Beijing, People’s Republic of ChinaCorrespondence: Ting YangDepartment of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Disease; Peking University Health Science Center; Institute of Respiratory Medicine, Chinese Academy of Medical SciencePeking University Health Science Center, No. 2 Yinghua East Street, Chaoyang District, Beijing, People’s Republic of ChinaTel +86 13651380809Email zryyyangting@163.comBackground: Indacaterol/glycopyrronium (IND/GLY) is a once-daily dual bronchodilator for long-term treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy and safety of IND/GLY have been proved before, but the cost-effectiveness is unknown in China.Purpose: This study assessed cost-effectiveness of IND/GLY comparing with salmeterol/fluticasone (SAL/FLU) and tiotropium.Methods: A patient-level simulation model was established from Chinese payer perspective. Patient parameters were randomly simulated through resampling from parameter distributions based on clinical trials and China-specific cost data to represent individual level health state and health state transitions in the model. We simulated patient-level health state, costs, life years (LYs) and quality-adjusted life years (QALYs) of whole life horizon to evaluate the cost-effectiveness of IND/GLY comparing with SAL/FLU and tiotropium respectively.Results: Comparing with SAL/FLU, IND/GLY resulted in 0.384 LYs and 0.255 QALYs gained. The incremental cost-effectiveness ratio (ICER) is − 35,822 CNY/LY and the incremental cost-utility ratio (ICUR) is − 53,834 CNY/QALY for IND/GLY versus SAL/FLU. Comparing with tiotropium, IND/GLY resulted in 0.232 LYs and 0.146 QALYs gained. The ICER is 39,729 CNY/LY and the ICUR is 63,246 CNY/QALY for IND/GLY versus tiotropium.Conclusion: This study found that dual bronchodilator IND/GLY is cost-effective for stable COPD treatment in China from Chinese payer’s perspective.Keywords: chronic obstructive pulmonary disease; COPD, dual bronchodilator, cost-effectiveness analysis, China

Siling Ren,1,* Jingxian Wu,2,* Wanchun Yin,1 Qianqian Liao,1 Sailan Gong,1 Beibei Xuan,1 Xiaoling Mu1 1Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Pathology, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this work.Correspondence: Xiaoling MuDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaEmail mxl@hospital.cqmu.edu.cnObjective: In this study, 345 patients with endometrial carcinoma (EC) were selected to investigate the correlation between ER/PR status and the EC disease-free survival (DFS) rate.Methods: The intensity and proportion of tumor cell expression of estrogen receptors and progesterone receptors (ER/PR) status of 345 postoperative tumor specimens in ECs were independently assessed semi-quantitatively by two pathologists using immunohistochemistry, the summed score ranged from 0 to 8 points was worked out by adding proportion score and intensity score based on the breast cancer hormone receptor immunohistochemical Allred scoring system. The association between DFS in ECs and ER/PR expression (intensity, proportion and summed score) was assessed using Cox regression analysis. Gene expression data were obtained from The Cancer Genome Atlas research network (TCGA).Results: According to inclusion criteria, 201 type I and 144 type II EC patients were enrolled in this study. In the univariate analysis of type I endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER/PR status on DFS is generally decreased but the correlation is still significant. In the univariate analysis of type II endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER status on DFS is generally decreased, but the correlation is still significant, the effect of PR expression on DFS is not statistically significant.Conclusion: Higher ER/PR expression status was associated with better DFS in patients with type I endometrial cancer after adjusting for known factors that significantly affect survival. In patients with type II endometrial cancer, patients with positive ER expression were significantly associated with better DFS. However, the effect of PR expression on DFS was not statistically significant.Keywords: endometrial cancer, endometrioid carcinoma, disease-free survival rate, hormone receptor status, ER, PR

Wei Liu,1 Xingquan Huang,1,2 Xiuying Zhang,1 Xiaoling Cai,1 Xueyao Han,1 Xianghai Zhou,1 Ling Chen,1 Rui Zhang,1 Siqian Gong,1 Yanai Wang,1 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of ChinaCorrespondence: Linong JiDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, No. 11, Xi Zhi Men Nan Street, Beijing 100044, People’s Republic of ChinaTel +86-10-88324108Fax +86-10-88324371Email jiln@bjmu.edu.cnPurpose: Latent autoimmune diabetes in adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of both type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), meaning that accurate and early diagnosis of this subtype of diabetes is critical for optimal long-term management. Urinary C-peptide creatinine ratio (UCPCR) represents a non-invasive and practical method for assessing endogenous insulin production to facilitate diabetes classification. However, no study to date has reported the use of UCPCR in identifying LADA.Patients and methods: A total of 574 subjects were included in our study (42 LADA, 61 T1DM, 471 T2DM). All participants were evaluated for UCPCR and underwent clinical and laboratory evaluations. UCPCR was compared among different subtypes of diabetes using multinomial regression analysis, and a receiver operating characteristic (ROC) curve was used to identify its performance in diagnosing LADA.Results: UCPCR was lower in LADA (0.4±0.6 nmol/mmol) compared with T2DM (1.2±0.9 nmol/mmol), but higher than in T1DM (0.2±0.3 nmol/mmol) (p

Gong S, Zhang J, Guo Z, Fu W. Drug Des Devel Ther. 2018;12:1865–1879. The Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of flow cytometry images in Figures 3A, 4E, 7C and 9E. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication nor were they able to provide the original flow cytometry data for their study. The Editor determined the results of the study were invalid and requested for the article to be retracted. The authors agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world.This article is part of a Special Issue entitled .

The dispensing performance of needle-type piezoelectric jet dispenser constitutes a crucial factor that ensures the quality of additive manufacturing processes. In this paper, a novel approach is proposed to enhance the dispensing performance of needle-type piezoelectric jetting dispensers by introducing a more adaptable driving waveform based on Bézier curves. Initially, the approach considers the electromechanical coupling effect of the needle-type piezoelectric dispenser and constructs a high-precision fluid–solid coupling model of the dispensing process. Subsequently, a multi-physics field joint simulation platform combining Matlab and Fluent is established to systematically analyze control strategies in real service conditions. Next, a new driving waveform based on Bézier curves is introduced, and the control parameters are optimized using a genetic algorithm to address issues such as air bubbles in the droplets and instability of the dispensing process. The optimized waveform based on the Bézier curve reduces the volume of air suction during the dispensing process by over 20% compared to the traditional waveform and eliminates the uncontrolled vibration state of the needle in the fluid, ensuring the stability of the entire fluid refill process. Finally, the optimized control strategy is verified through experiments and compared with traditional methods. The experiment demonstrates its advantages in addressing issues with no air bubbles in the droplets and consistency of the droplets. This study provides valuable insights into optimizing the dispensing performance of needle-type piezoelectric jetting dispensers regarding control strategy. [ABSTRACT FROM AUTHOR]

Wanfu Men,1 Peiyao Zhu,1 Siyuan Dong,1 Wenke Liu,1 Kun Zhou,1 Yu Bai,1 Xiangli Liu,1 Shulei Gong,1 Can Yang Zhang,2 Shuguang Zhang1 1Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210, USACorrespondence: Shuguang ZhangDepartment of Thoracic Surgery, The First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, People’s Republic of ChinaTel +86 13909886618Email shgzhang@cmu.edu.cnCan Yang ZhangSingapore-MIT Alliance for Research and Technology, 1 Create Way, #03-12/13/14 Enterprise Wing, Singapore 138602, SingaporeTel +65 9499 0710Email canyang.zhang@smart.mit.eduBackground: The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance.Methods: In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pKb value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility.Results: The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX.Conclusion: All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.Keywords: pH-sensitive, redox-sensitive, lipid-polymer, hybrid, drug delivery, anticancer, stimuli-responsiveness

Yunli Shen,1,* Shiyu Gong,1,* Jiming Li,1,* Yunkai Wang,1 Xumin Zhang,1 Hao Zheng,1 Qi Zhang,1 Jieyun You,1 Zheyong Huang,2 Yihan Chen11Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, People’s Republic of China; 2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs.Methods and results: Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe3O4 nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis.Conclusions: NAC modifying could suppress the toxic effects of Fe3O4 nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.Keywords: N-acetylcysteine (NAC), iron oxide nanoparticles, oxidative stress, cardiomyocytes, hypoxia-reoxygenation

Linya Guo,1,* Yanbing Li,2,3,* Ying Tian,4,5,* Shaoxin Gong,6 Xi Chen,1 Tianhong Peng,1 Aiping Wang,1,4,5,7 Zhisheng Jiang71Clinical Anatomy & Reproductive Medicine Application Institute, School of Medicine, University of South China, Hengyang 421001, People’s Republic of China; 2National Key Discipline of Human Anatomy, Southern Medical University, Guangzhou 510000, Guangdong, People’s Republic of China; 3Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangzhou, 510000, Guangdong, People’s Republic of China; 4Institute of Clinical Research, Affiliated Nanhua Hospital, University of South China, Hengyang 421002, Hunan, People’s Republic of China; 5Postdoctoral Research Institute on Basic Medicine, University of South China, Hengyang, 421001, Hunan, People’s Republic of China; 6Department of Pathology, First Affiliated Hospital, University of South China, Hengyang 421001, Hunan, People’s Republic of China; 7Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang 421001, Hunan, People’s Republic of China*These authors contributed equally to this workPurpose: Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy.Methods: We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs.Results: Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs.Conclusion: Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway.Keywords: eIF2α, autophagy, PASMCs, PAH, monocrotaline

Xiangyi Kong,1,2,* Shun Gong,3–5,* Tao Yan,6,* Yi Yang1 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 3Department of Neurosurgery, The General Hospital of Shenyang Military, Army Institute of Neurology, Shenyang 110016, People’s Republic of China; 4Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 5Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 6Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China *These authors contributed equally to this work Aim: To elucidate the clinical implication of microRNA (miRNA)-200b in the pathological grading of gliomas.Methods: We searched the Chinese National Knowledge Infrastructure, Web of Knowledge, Embase, and PubMed databases. Related articles were assessed, and ORs with 95% CIs were calculated to examine the relationship between miRNA-200b expression levels and the World Health Organization (WHO) glioma grade, patients’ sex and age, tumor size, and extent of surgical resection. Heterogeneity, publication bias, and stability of the pooled results of the included studies were also analyzed. MiR-200b expression in 87 human glioma tissues (50 high grade and 37 low grade) and matched 41 non-neoplastic brain tissues was measured by real-time quantitative RT-PCR assay.Results: Five eligible studies involving 630 patients were included in the present meta-analysis. The miRNA-200b expression in glioma tissues was negatively associated with the WHO glioma grade (OR, 0.070; 95% CI, 0.007–0.678; P=0.022). No significant correlations were found between miRNA-200b and sex (P=0.858), age (P=0.776), tumor size (P=0.134), or extent of resection (P=0.778). In our own test, compared with non-neoplastic brain tissues, the expression level of miR-200b was significantly decreased in glioma tissues (tumor vs normal: 4.29±1.90 vs 10.45±2.34, P

Shenglan Gong,1 Jin Zhang,2 Zhouke Guo,3 Wenjun Fu1 1South China Research Center for Acupuncture and Moxibustion, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People’s Republic of China; 2Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People’s Republic of China; 3Department of Neurology and Psychology, Shenzhen Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, People’s Republic of China Background: Depression is characterized by a pathological injury to the hippocampal neurons. Senkyunolide A (SenA) is one of the major active components of Dan-zhi-xiao-yao-san, which is widely used in the treatment of depression-related disorders.Materials and methods: In the present study, it was hypothesized that the antidepressant effect of Dan-zhi-xiao-yao-san depended on the function of SenA and the authors attempted to reveal the molecular mechanism associated with the treatment. An in vitro depression model was induced using corticosterone (Cort), and the effect of SenA on the cell viability, apoptosis, and protein phosphatase 2A/α-synuclein (PP2A/α-syn) signaling was detected. To validate the mechanism driving the therapeutic effect of SenA, activity of PP2A and α-syn was modulated and the effect on neural cells was evaluated.Results: The results showed that SenA protects Cort-induced cell apoptosis in PC12 cells. In addition, SenA increased Cort-induced reduction of PP2A activity, while it decreased the expression of p-PP2A, α-syn, and p-α-syn (Ser129). Further, modulation of PP2A activity with specific inhibitor okadaic acid (OA) increased Cort-induced cell apoptosis, while PP2A activator D-erythro-sphingosine (SPH) exhibited an opposite effect. The neuroprotective effects of SenA on neural cells also depended on inhibition of α-syn function, the regulation of which would influence the activity of PP2A in a negative loop.Conclusion: Collectively, the results suggested that the neuroprotective effects of SenA were exerted by modulating activities of PP2A activities and α-syn. The findings partially explained the mechanism associated with the neuroprotective effect of SenA. Keywords: α-synuclein, corticosterone, depression, neuroprotection, protein phosphatase 2A, senkyunolide A

BACKGROUND/OBJECTIVES: Data regarding the relationships between body mass index (BMI) and brain tumors are inconsistent, especially for the commonly seen gliomas and meningiomas. Therefore, we conducted a dose-response meta-analysis to unravel the issue. SUBJECTS/METHODS: Cochrane Library, PubMed and Embase were searched for pertinent case-control and cohort studies updated to November 2014. Dose-response and quantitative analysis were conducted with random-effect model. RESULTS: Sixteen studies were included, containing 3 887 156 participants and 11 614 cases. In categorical analysis for the relationships between abnormal weight and BMI, the summary risk ratio (RR) of brain tumors was 1.34 (95% confidential interval (CI), 1.15-1.56) for obesity, 1.12 (95% CI, 1.05-1.19) for overweight and 0.77 (95% CI, 0.64-0.93) for underweight; the summary RR of gliomas was 1.13 (95% CI, 1.02-1.26) for overweight and 0.71 (95% CI, 0.58-0.88) for underweight; the summary RR of meningiomas was 1.48 (95% CI, 1.30-1.69) for obesity and 1.18 (95% CI, 1.07-1.31) for overweight. In dose-response analysis, for every 5 kg/[m.sup.2] increment of BMI, the summary RR was 1.13 (95% CI, 1.07-1.20) for overall brain tumors, 1.07 (95% CI, 0.97-1.19) for gliomas and 1.19 (95% CI, 1.14-1.25) for meningiomas. CONCLUSIONS: Excess weight was associated with increased risk of brain tumors and meningiomas but not with gliomas. Selective screening for brain tumors among obesity, especially for the females, might be more instructive. European Journal of Clinical Nutrition (2016) 70, 757-765; doi: 10.1038/ejcn.2016.4; published online 24 February 2016, INTRODUCTION According to the World Health Organization, in 2008, more than 1.4 billion adults, 20 and older, were overweight; more than 11% of the world's adults were obese; 42 million [...]