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Yanting Ma,1 Yongyuan Li,2 Zhanfeng Zhang,3 Guomei Du,4 Ting Huang,1 Zhi Zhong Zhao,5 Shou Liu,1 Zhancui Dang1 1Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Disease Control department, Huangzhong District health Bureau, Xining, Qinghai, People’s Republic of China; 3Huangzhong District, Duoba County Health Services Center, Xining, Qinghai, People’s Republic of China; 4Clinical Laboratory, Qinghai Red Cross Hospital, Xining, Qinghai, People’s Republic of China; 5Disease Control Department, Qinghai Provincial Center for Endemic Disease Control and Prevention, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Shou Liu; Zhancui Dang, Email liushou2004@aliyun.com; yxyyy2019@163.comPurpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China.Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation.Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies.Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.Keywords: metabolic syndrome, nomogram, prediction model, plateau section

Jinzhu Huang,* Jinxin Zhao,* Miao Yi, Yaling Yuan, Peiwen Xia, Bingxue Yang, Jiajia Liao, Zijun Dang, Yun Xia* Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Xia, Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13668043942, Fax +86-23-89012513, Email xiayun12cn@aliyun.comPurpose: This research aims to profile ten novel strains of carbapenem-resistant Enterobacteriaceae (CRE) co-carrying blaKPC and blaNDM.Methods: Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics.Results: During the course of this research, ten clinical CRE strains co-carrying blaKPC and blaNDM were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 existed concurrently within a single Citrobacter freundii strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 were transferred by Tn 5393, IS 5, and Tn 6296, respectively.Conclusion: This research presents the first report of coexistence of tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 in a carbapenem and tigecycline-resistant C. freundii strain, CF10.Importance: Tigecycline is considered a “last resort” antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1, which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these “superbugs”.Keywords: blaKPC, blaNDM, carbapenem-resistantEnterobacteriaceae, tigecycline-resistance, tmexCD 1-toprJ 1

Xiangqian Xu,1,2,* Zhongqin Dang,2,* Junping Zhang,3 Yingpu Feng,4 Zheng Wei1,3 1Gastroenterology Department, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China; 2Gastroenterology Department, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450002, People’s Republic of China; 3Oncology Department, Henan Academy Institute of Traditional Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China; 4Oncology Department, Henan Province People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingpu Feng Email fengyingpu888@163.comZheng Wei Email questwz@163.comObjective: To investigate the function and the mechanism of miR-125b in the invasion and metastasis of gastric cancer and provide experimental basis for finding and developing new therapeutic strategies for gastric cancer.Methods: The difference of miR-125b expression in gastric cancer tissues and adjacent tissues was detected by qRT-PCR. The same test was performed in different gastric cancer cell lines. The effect of miR-125b on SGC-7901 and BGC-823 gastric cancer cell viability was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Transwell assay was used to detect the effect of miR-125b on invasion and metastasis of gastric cancer cells. The target gene STAT3 of miR-125b was identified and validated by dual luciferase reporter assay. Western blot assay and immunofluorescence staining were used to detect the effect of miR-125b on the expression and distribution of STAT3 protein. The inhibitor and activator of STAT3 were used to confirm the effect of STAT3 on invasion and metastasis of gastric cancer cells. Peritoneal metastasis experiment and IHC were used to study the inhibitory effect of miR-125b on the metastasis of gastric cancer in vivo.Results: The results of qRT-PCR showed that 125b expression was significantly lower in gastric cancer than in adjacent tissues, which indicated poor prognosis for gastric-cancer patients. Furthermore, two gastric-cancer cell lines, SGC-7901 and BGC-823, exhibited lower miR-125b levels than the normal cell line HEK293. After treatment with miR-125b mimics, cell proliferation was markedly inhibited. Meanwhile, the invasion and metastasis of gastric cancer cells were also inhibited after treated with miR-125b mimics. We also identified the signal transducer and activator of transcription 3 (STAT3) as a potential target of miR-125b based on patient data from The Cancer Genome Atlas (TCGA). Dual luciferase assays revealed that miR-125b directly inhibited STAT3 by binding to its 3′-untranslated region (UTR). Immunofluorescence assay showed that miR-125b could affect the subcellular distribution of STAT3. Moreover, treatment with miR-125b mimics or stattic inhibited invasion and migration in the gastric cancer cell lines, and IL-6 could reverse the inhibitory effect. Finally, nude mice xenografted with gastric-cancer cells expressing miR-125b mimics exhibited smaller tumors and lower transfer rates than mice engrafted with control group cells.Conclusion: These data suggested that miR-125b inhibited invasion and metastasis in gastric cancer by inhibiting STAT3; therefore, miR-125b and STAT3 could be potential therapeutic targets in the treatment of gastric cancer.Keywords: miR-125b, invasion and metastasis, gastric cancer, STAT3

Yuxing Cai,1 Yi Hao,2 HaiFeng Ren,3 ZhiGuo Dang,3 Hui Xu,1 Xiangfei Xue,1 Yan Gao3 1Department of Respiratory Medicine, Baoji Central Hospital, Baoji, 721008, People’s Republic of China; 2Department of Pediatric Surgery, Baoji Maternal and Child Health Hospital, Baoji, 721008, People’s Republic of China; 3Department of Respiratory Medicine, People Hospital BaoJi City, Baoji, 721001, People’s Republic of ChinaCorrespondence: Yan GaoDepartment of Respiratory Medicine, People Hospital BaoJi City, No. 24 Xinhua Street, Weibin District, Baoji City, Shanxi Province 721001, People’s Republic of ChinaEmail zhungao703730393@126.comBackground: Increasing evidence has suggested the critical implication of microRNAs (miRNAs) in the initiation and progression of non-small cell lung cancer (NSCLC). Previous studies have shown the tumor-suppressive function of miR-1305 in cancer; however, the role of miR-1305 in NSCLC has not been fully understood.Methods: The expression of miR-1305 in NSCLC was detected by RT-qPCR. The influence of miR-1305 on the growth of NSCLC cells was determined via Cell Counting Kit 8 (CCK-8), colony formation and FACS analysis. The targets of miR-1305 were predicted with the miRDB database. Luciferase reporter assay was performed to investigate the binding between miR-1305 and 3ʹ-UTR of MDM2. Western blot was applied to check the expression of MDM2 with miR-1305.Results: Here, we found that miR-1305 was down-regulated in NSCLC tissues and cell lines. Decreased miR-1305 was significantly correlated with the metastasis and poor prognostics of NSCLC patients. Overexpression of miR-1305 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Bioinformatics and luciferase assay uncovered that the mouse/murine double minute 2 (MDM2) was a target of miR-1305. miR-1305 bound the 3ʹ-untranslated region (UTR) of MDM2 and decreased the expression of MDM2 in NSCLC cells. As MDM2 was a negative regulator of p53, decreased MDM2 by miR-1305 up-regulated the abundance of p53 in NSCLC cells. Restoration of MDM2 markedly attenuated the suppressive role of miR-1305 in the proliferation and migration of NSCLC cells.Conclusion: The findings provided novel mechanism of miR-1305/MDM2 signaling in regulating the progression of NSCLC, suggesting miR-1305 as a promising target for the treatment of NSCLC.Keywords: NSCLC, miR-1305, MDM2, p53

Zhibo Dang,1,2,* Xiaoli Liu,1,* Xinhui Wang,1 Mengge Li,1,2 Yuyong Jiang,1 Xianbo Wang,1 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Chaoyang District, Beijing 100015, People’s Republic of China; 2First Clinical Medical College, Beijing University of Chinese Medicine, Chaoyang District, Beijing 100029, People’s Republic of China *These authors contributed equally to this work Abstract: A systematic review and meta-analysis of previous randomized controlled trials of traditional Chinese medicine (TCM) supporting Qi and enriching blood in the treatment of cancer related anemia (CRA) in patients not receiving chemoradiotherapy were conducted. A total of 13 randomized controlled trials were included. Compared with the control group, better improvement was found for the level of hemoglobin (mean difference=4.57, 95% CI [1.38, 7.76], P=0.005) and overall therapeutic effect (risk ratio [RR]=1.31, 95% CI [1.18, 1.46], P

Objective: A qualitative study was conducted to gain insight into challenges reported by Butaleja households during a previous household survey. Specifically, this paper discusses heads of households’ and caregivers’ perceptions of challenges they face when seeking care for their very young children with fever presumed to be malaria. Methods: Eleven focus groups (FGs) were carried out with household members (five with heads of households and six with household caregivers) residing in five sub-counties located across the district. Purposive sampling was used to ensure the sample represented the religious diversity and geographical distance from the peri-urban center of the district. Each FG consisted of five to six participants. The FGs were conducted at a community centre by two pairs of researchers residing in the district and who were fluent in both English and the local dialect of Lunyole. The discussions were recorded, translated, and transcribed. Transcripts were reviewed and coded with the assistance of QDA Miner (version 4.0) qualitative data management software, and analyzed using thematic content analysis. Results: The FG discussions identified four major areas of challenges when managing acute febrile illness in their child under the age of five with presumed malaria: (1) difficulties with getting to public health facilities due to long geographical distances and lack of affordable transportation; (2) poor service once at a public health facility, including denial of care, delay in treatment, and negative experiences with the staff; (3) difficulties with managing the child’s illness at home, including challenges with keeping home-stock medicines and administering medicines as prescribed; and (4) constrained to use private outlets despite their shortcomings. Conclusions: Future interventions may need to look beyond the public health system to improve case management of childhood malaria at the community level in rural districts such as Butaleja. Given the difficulties with accessing quality private health outlets, there is a need to partner with the private sector to explore feasible models of community-based health insurance programs and expand the role of informal private providers.

OBJECTIVE: This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases. MATERIALS AND METHODS: PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed. RESULTS: The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147). CONCLUSIONS: The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype. [ABSTRACT FROM AUTHOR]