Search

Shengyang Liu,1 Hui Zhao,2 Li Shi,1 Hongzhi Ji1 1Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Radiology, Shandong Second Provincial General Hospital, Jinan, People’s Republic of ChinaCorrespondence: Hongzhi Ji, Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, 4 Duanxing West Road, Jinan, 250000, People’s Republic of China, Email jhz_jx163@163.comAbstract: In this case report, we describe a 21-year-old man with recurrent hemangiomas in his left eye socket and nasal cavity. Traditional surgeries were unsuccessful, so we used Bevacizumab, a drug that inhibits blood vessel growth. This approach significantly reduced the tumor size and stopped frequent nosebleeds. Over two years, the tumor remained controlled without major side effects, suggesting Bevacizumab as a promising non-surgical treatment for recurrent hemangiomas.Keywords: Bevacizumab, orbital hemangioma, vascular endothelial growth factor, treatment efficacy

Yan Wu,1 Zhenzhen Xu,2 Jing Dong,3 Wenzhong Zhang,2 Jing Li,2 Hong Ji1 1Department of Nursing, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, Shandong, 250014, People’s Republic of China; 2School of Nursing, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 3School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong Province, 271016, People’s Republic of ChinaCorrespondence: Hong Ji, Department of Nursing, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, Shandong, 250014, People’s Republic of China, Tel +86-13791120369, Email honghongji-2005@163.comBackground: Older age and female sex are risk factors for osteoarthritis and osteoporosis (OP). This study evaluated the knowledge, attitudes, and practices of patients with knee osteoarthritis (KOA) in China regarding OP and its prevention. This cross-sectional, questionnaire-based study enrolled patients with KOA at four grade-A tertiary hospitals in Shandong Province between 1st September and 20th November 2022.Methods: The administered questionnaire contained 55 items across four dimensions (demographic information, knowledge, attitude, and practice). Logistic regression analyses were performed to identify factors associated with an overall questionnaire score ≥ 70% of the maximum possible score. SPSS 26.0 was used for the analyses; P< 0.05 was considered significant.Results: The analysis included 434 participants (261 females). The median knowledge, attitude, and practice scores were 7 (interquartile range: 5– 10) (possible range, 0– 17 points), 44 (interquartile range: 42– 49) (possible range, 11– 55 points), and 43 (interquartile range: 38– 47) (possible range, 13– 65 points), respectively. Multivariable logistic regression indicated that female sex (odds ratio [OR], 2.421; 95% confidence interval [95% CI] 1.558– 3.762; P< 0.001), age 56– 65 years-old (OR, 4.222; 95% CI, 1.763– 10.109; P=0.001 vs ≤ 55 years-old), age > 65 years-old (OR, 4.358; 95% CI, 1.863– 10.195; P=0.001 vs ≤ 55 years-old), middle/high/technical secondary school education (OR, 1.853; 95% CI, 1.002– 3.428; P=0.049 vs primary school or below), and having KOA for 4– 5 years (OR, 2.682; 95% CI, 1.412– 5.094; P=0.003 vs ≤ 3 years) were independently associated with a high KAP score.Conclusion: There is room for improvement in the knowledge and practices of patients with osteoarthritis in China regarding OP. The findings of this study may facilitate the design and implementation of education programs to increase awareness about OP prevention among patients with KOA.Keywords: osteoarthritis of the knee, osteoporosis, disease prevention, surveys and questionnaires, health knowledge, attitudes, practice

Aims: Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation. Methods: This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR. Results: From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy. Conclusion: This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation. Cite this article: Bone Joint Res 2024;13(7):315–320.

Hua Ji,1,&ast; YaTing Lu,1,&ast; Gui Liu,2 Xiaotong Zhao,1 Murong Xu,1 Mingwei Chen1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 2Department of Endocrinology, The Second People’s Hospital of Lu’an City, Lu’an City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei Chen, Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei City, Anhui Province, People’s Republic of China, Email chmw1@163.comObjective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN.Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value.Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency.Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.Keywords: miR-155, miR-146a, diabetic peripheral neuropathy, type 2 diabetes mellitus, biomarkers

Jiemei Ye,1,2,&ast; Xiaoying Huang,3,4,&ast; Weiling Qin,1,2,&ast; Pan Liang,3,4 Jun Zhao,4 Yinxin Ye,1,2 Huojin Ji,1,2 Xinyun Peng,1,2 Yushan Liang,3,4 Yonglin Cai1,5 1Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 2Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonglin Cai, Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, 543002, People’s Republic of China, Email cylzen@163.com Yushan Liang, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email yushanliang33@outlook.comPurpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC.Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis.Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice.Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.Keywords: nasopharyngeal carcinoma, transcription factor, PAX5, prognosis, immunity, Epstein-Barr virus

Yiwen Zhang,1 Wei Wang,2,&ast; Lili Xu,1 Zhexun Lian,3 Jiale Huang,4 Yaowei Chang,5 Junjie Guo,3 Yangang Wang,1,&ast; Kexiu Song,6 Hongwei Ji7,8,&ast; 1Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of International Medicine, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China; 8Department of Internal Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangang Wang, Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email wangyg@qdu.edu.cn Hongwei Ji, Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China, Email hongweijicn@gmail.com

Abstract A high-performance H2 gas sensor system based on capacitive electrodes and a volumetric analysis technique were developed. Coaxial capacitive electrodes were fabricated by placing a thin copper rod in the center and by adhering a transparent conductive film on the exterior surface of a graduated cylinder. Thus, H2 from a polymer specimen lowered the water level in the cylinder between the two electrodes, producing measurable changes in capacitance that allowed for the measurement of the H2 concentration emitted from the specimen enriched by H2 under high-pressure conditions. The sensing system detected diffused/permeated hydrogen gas from a specimen and hydrogen gas leaks caused by imperfect sealing. The hydrogen gas sensor responded almost instantly at 1 s and measured hydrogen concentrations ranging from 0.15 to 1500 ppm with controllable sensitivity and a measurable range. In addition, performance tests with polymer specimens used in hydrogen infrastructure verified that the sensor system was reliable; additionally, it had a broad measurement range to four decimal places. The sensor system developed in this study could be applied to detect and characterize pure gases (He, N2, O2 and Ar) by real time measurement.

Yaxin Guo,1 Haiyan Ji,1 Junfeng Liu,1 Yong Wang,1 Jinming Liu,1 Hong Sun,1 Yuanhui Fei,1 Chunhui Wang,1 Tieliang Ma,2 Chao Han1,3 1Department of Anesthesiology, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 3Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, 214200, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86 13961568178, Fax +86 051087921010, Email staff940@yxph.comPurpose: This study aimed to develop and validate a post-operative delirium (POD) nomogram in a population of elderly patients undergoing elective orthopedic surgery.Patients and Methods: A predictive model was developed based on a training dataset of 474 elderly patients undergoing elective orthopedic surgery from March 2021 to May 2022. POD was identified using the Confusion Assessment Methods (CAM). The least absolute shrinkage and selection operator (LASSO) method was used to screen risk factors, and prediction models were created by combining the outcomes with logistic regression analysis. We employ bootstrap validation for internal validation to examine the model’s repeatability. The results were validated using a prospective study on 153 patients operated on from January 2022 to May 2022 at another institution.Results: The predictors in the POD nomogram included age, the Mini-Mental State Examination(MMSE), sleep disorder, neurological disorders, preoperative serum creatinine (Pre-SCR), and ASA classification. The c-index of the model was 0.928 (95% confidence interval 0.898 ~ 0.957) and the bootstrap validation still achieved a high c-index of 0.912. The c-index of the external validation was 0.921. The calibration curve for the diagnostic probability showed good agreement between prediction by nomogram and actual observation.Conclusion: By combining preoperative and intraoperative clinical risk factors, we created a POD risk nomogram to predict the probability of POD in elderly patients who undergo elective orthopedic surgery. It could be a tool for guiding individualized interventions.Keywords: post-operative delirium, elderly, elective orthopedic surgery, predictive models, nomogram

Hongxiang Ji,1 Ziyi Zhao,2 Zeyu Liu,3 Ruitao Sun,3 Yuquan Li,1 Xiaoheng Ding,2 Tongshang Ni4 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Hand and Foot, Microsurgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3School of Clinical Medicine, Department of Medicine, Qingdao University, Qingdao, People’s Republic of China; 4Center of Integrated Traditional Chinese and Western Medicine, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Tongshang Ni, Center of Integrated Traditional Chinese and Western Medicine, School of Basic Medicine, Qingdao University, No. 308, Ningxia Road, Qingdao, Shandong, People’s Republic of China, Email neetongshang@126.com Xiaoheng Ding, Department of Hand and Foot, Microsurgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, Shandong, People’s Republic of China, Email dxhqd@126.comAim: To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment.Methods: This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment.Results: Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04± 0.82% at baseline to 8.30± 0.99% and 8.00± 0.80% at the end, p< 0.001), FPG (165.6± 40.2 mg/dL at baseline to 157.1± 36.3mg/dL and 143.6± 32.3mg/dL at the end, p< 0.001), weight (74.7± 7.1kg at baseline to 74.8± 10.0kg and 73.6± 8.1kg at the end, p< 0.001), insulin dose (49.3± 10.8U/d at baseline to 46.7± 8.0U/d and 45.2± 8.7U/d, p< 0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c< 7%. The most common adverse event is hypoglycemia.Conclusion: HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, β-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.Keywords: type 2 diabetes, observational study, hydrogen inhalation, glycemic control, real-world study

Chao Han,1,2 Haiyan Ji,1 Yaxin Guo,1 Yuanhui Fei,1 Chunhui Wang,1 Yanbo Yuan,1 Zhihui Ruan,1 Tieliang Ma1,2 1Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, 214200, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86 13961568178, Fax +86 051087921010, Email staff940@yxph.comBackground: Perioperative neurocognitive disorders (PND), including delayed neurocognitive recovery (dNCR) and postoperative cognitive dysfunction (POCD), are common postoperative complications in elderly patients and adversely affect their prognosis. The study was designed to explore the effects of esketamine on postoperative cognitive function in elderly patients who underwent gastrointestinal surgery under general anesthesia and its potential mechanism.Methods: Eighty-four patients aged 65 and above undergoing gastrointestinal surgery were randomly divided into 2 groups: the esketamine group (group S) and the control group (group C). Group S received intravenous sub-anesthetic doses of esketamine (0.15 mg/kg) 5 minutes before the initiation of surgery, while group C received the same volume of saline. A battery of neuropsychological tests was used to assess cognitive function before surgery, 7 days, and 3 months after surgery. The primary outcome was the incidence of dNCR at 7 days postoperatively and POCD at 3 months postoperatively in both groups. The secondary outcome measures included changes in the levels of serum interleukin-6 (IL-6) and calcium-binding protein β (S100β) before and 1 day after surgery.Results: The incidence of dNCR in group S was lower than that of group C (18.15% vs 38.24% P=0.033). Contrarily, there was no difference in both groups regarding POCD 3 months postoperatively (6.06% vs 14.37% P=0.247). Plasma IL-6 and S100β levels were significantly elevated in both groups on postoperative day 1 (p< 0.05), but esketamine pretreatment reduced these levels to some extent compared with group C (p< 0.05).Conclusion: Sub-anesthetic doses of esketamine might reduce the incidence of dNCR and improve early postoperative cognitive function in elderly patients undergoing gastrointestinal surgery, which might be related to the anti-neuroinflammation effects of esketamine.Keywords: esketamine, perioperative neurocognitive disorders, gastrointestinal surgery, elderly, neuroinflammatory

IntroductionTrauma patients are susceptible to coagulopathy and dysfunctional immune responses. Mesenchymal stromal cells (MSCs) are at the forefront of the cellular therapy revolution with profound immunomodulatory, regenerative, and therapeutic potential. Routine assays to assess immunomodulation activity examine MSC effects on proliferation of peripheral blood mononuclear cells (PBMCs) and take 3–7 days. Assays that could be done in a shorter period of time would be beneficial to allow more rapid comparison of different MSC donors. The studies presented here focused on assays for MSC suppression of mitogen-stimulated PBMC activation in time frames of 24 h or less.MethodsThree potential assays were examined—assays of apoptosis focusing on caspase activation, assays of phosphatidyl serine externalization (PS+) on PBMCs, and measurement of tumor necrosis factor alpha (TNFα) levels using rapid ELISA methods. All assays used the same initial experimental conditions: cryopreserved PBMCs from 8 to 10 pooled donors, co-culture with and without MSCs in 96-well plates, and PBMC stimulation with mitogen for 2–72 h.ResultsSuppression of caspase activity in activated PBMCs by incubation with MSCs was not robust and was only significant at times after 24 h. Monitoring PS+ of live CD3+ or live CD4+/CD3+ mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, 2 h, although no increase in the percentage of PS+ cells was seen with time. The ability of MSC in co-culture to suppress PBMC PS+ externalization compared favorably to two concomitant assays for MSC co-culture suppression of PBMC proliferation, at 72 h by ATP assay, or at 96 h by fluorescently labeled protein signal dilution. TNFα release by mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, with accumulating signal over time. However, suppression levels with MSC co-culture was reliably seen only after 24 h.DiscussionTakeaways from these studies are as follows: (1) while early measures of PBMC activation is evident at 2–6 h, immunosuppression was only reliably detected at 24 h; (2) PS externalization at 24 h is a surrogate assay for MSC immunomodulation; and (3) rapid ELISA assay detection of TNFα release by PBMCs is a robust and sensitive assay for MSC immunomodulation at 24 h.

Jiao Meng,1,&ast; Hongyan Ji,2,&ast; Liting Chen,2 Aichun Liu1 1Hematology Department, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aichun Liu, Hematology Department, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, People’s Republic of China, Tel +86-451-13633611958, Email aichun2002@hotmail.com Liting Chen, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86-27-13339999679, Email ltchen@tjh.tjmu.edu.cnPurpose: The aim of this study was to examine and compare the differences between droplet digital PCR (ddPCR) and metagenomic next-generation sequencing (mNGS) in the detection of human herpesvirus 6B (HHV-6B). Long-term monitoring of HHV-6B viral load in patients receiving chimeric antigen receptor-modified T-cell (CAR-T) therapy and hematopoietic stem cell transplantation (HSCT) can be used to identify immune effector cell-associated neurotoxicity syndrome (ICANS) and guide drug therapy.Methods: Twenty-seven patients with suspected HHV-6B infection who had both mNGS and ddPCR test results were analyzed retrospectively, including 19 patients who received CAR T-cell therapy and 8 who received HSCT. The HHV-6B probe and primers were designed, and the performance of the ddPCR assay was evaluated. Subsequently, ddPCR was performed utilizing blood and urine. Data on clinical information and mNGS investigations were collected.Results: The ddPCR test results correlated significantly with the mNGS test results (P < 0.001, R2 = 0.672). Of the 27 time-paired samples, ddPCR showed positive HHV-6B detection in 20 samples, while mNGS alone showed positive HHV-6B detection in 12 samples. ddPCR detected additional HHV-6B infections in 8 samples that would have been missed if only mNGS were used. In addition, the first HHV-6B infection event was detected at a median of 14 days after CAR T-cell infusion (range, 8 to 19 days). Longitudinal monitoring of HHV-6B by ddPCR was performed to assess the effectiveness of antiviral therapy. The data showed that with antiviral treatment HHV-6B viral load gradually decreased.Conclusion: Our results indicated that ddPCR improved the HHV-6B positive detection ratio and was an effective adjunct to mNGS methods. Furthermore, the longitudinal detection and quantification of HHV-6B viral load in patients undergoing CAR T-cell therapy and HSCT may serve as a guide for drug treatment.Keywords: droplet digital PCR, CAR T-cell therapy, HSCT, infection, HHV-6B, mNGS

ABSTRACT Objective: The risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy (FNAB) of thyroid nodules (TN) with diameters ≥ 3-4 cm remains controversial. However, some groups have indicated surgical treatment in these patients regardless of the FNAB results. We aimed to evaluate the diagnostic accuracy of the FNAB in systematically resected ≥4 cm TN and if the risk of malignancy is higher in these patients. Subjects and methods: We retrospectively evaluated 138 patients (142 nodules) with TN with diameters ≥4 cm who underwent thyroidectomy. Results: The FNAB results were nondiagnostic/unsatisfactory (ND/UNS) in 2.1% of the cases and benign in 51.4%. They indicated atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 23.9% of cases, follicular neoplasia/suspicious for a follicular neoplasm (FN/SFN) in 9.2%, suspicion of malignancy (SUS) in 8.5%, and malignant in 4.9%. The histopathological analysis after thyroidectomy revealed a thyroid cancer rate of 100% in the FNABs classified as malignant, 33.3% in SUS cases, 7.7% in FN/SFN, 17.6% in AUS/FLUS, and 4.1% in benign FNABs. None of the ND/UNS FNABs were malignant. The global malignancy diagnosis was 14.8% (n = 21). However, the rate of false negatives for FNAB was low (4.1%). Conclusion: We showed that the risk of malignancy in nodules with diameters ≥4 cm was higher compared to the risk of thyroid cancer in TN in general. However, we found a low rate of false-negative cytological results; therefore, our data do not justify the orientation of routine resection for these larger nodules.

Xu Li,1 Huifan Ji,1 Dezhi Zhang,2 Meishan Jin,3 Xiaolin Guo,1,&ast; Pujun Gao1,&ast; 1Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Abdominal Ultrasound, The First Hospital of Jilin University, Jilin University, Changchun, 130021, People’s Republic of China; 3Department of Pathology, The First Hospital of Jilin University, Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolin Guo; Pujun Gao, Email gpj@jlu.edu.cnBackground: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic tumor that is poorly understood. It is not associated with specific physical findings and is usually diagnosed incidentally, resulting in tumors that are often large-sized at diagnosis. At present, the main treatment approach is surgical resection.Case Presentation: Here, we report the case of a patient with LELCC treated with microwave ablation (MWA). Our patient was a Chinese man with chronic hepatitis C and a 51 mm-diameter intrahepatic tumor. Despite blood testing, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, and abdominal ultrasound, the tumor was not well diagnosed. However, the histopathological findings of ultrasound-guided percutaneous tumor biopsy led to a diagnosis of LELCC. The patient was treated with MWA, and no new lesions had occurred at 9 months after treatment.Conclusion: To our knowledge, this is the first patient with LELCC treated using MWA. Our experience suggests that MWA is an effective new therapeutic method for this disease.Keywords: Epstein-Barr virus, lymphoepithelioma-like cholangiocarcinoma, microwave ablation, hepatitis C, liver tumor

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Aims: This study aimed to identify the effect of anatomical tibial component (ATC) design on load distribution in the periprosthetic tibial bone of Koreans using finite element analysis (FEA). Methods: 3D finite element models of 30 tibiae in Korean women were created. A symmetric tibial component (STC, NexGen LPS-Flex) and an ATC (Persona) were used in surgical simulation. We compared the FEA measurements (von Mises stress and principal strains) around the stem tip and in the medial half of the proximal tibial bone, as well as the distance from the distal stem tip to the shortest anteromedial cortical bone. Correlations between this distance and FEA measurements were then analyzed. Results: The distance from the distal stem tip to the shortest cortical bone showed no statistically significant difference between implants. However, the peak von Mises stress around the distal stem tip was higher with STC than with ATC. In the medial half of the proximal tibial bone: 1) the mean von Mises stress, maximum principal strain, and minimum principal strain were higher with ATC; 2) ATC showed a positive correlation between the distance and mean von Mises stress; 3) ATC showed a negative correlation between the distance and mean minimum principal strain; and 4) STC showed no correlation between the distance and mean measurements. Conclusion: Implant design affects the load distribution on the periprosthetic tibial bone, and ATC can be more advantageous in preventing stress-shielding than STC. However, under certain circumstances with short distances, the advantage of ATC may be offset. Cite this article: Bone Joint Res 2022;11(5):252–259.

Dan Guo,1,&ast; Lemin Hong,1,&ast; Hao Ji,2,&ast; Yuwen Jiang,1 Ling Lu,1 Xinfeng Wang,1 Hongming Huang1 1Department of Hematology, The Affiliated Hospital of Nantong University, Jiangsu, People’s Republic of China; 2Department of Urology, Tumor Hospital Affiliated to Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Wang; Hongming Huang, Department of Hematology, The Affiliated Hospital of Nantong University, No. 20, Xisi Street, Nantong, 226001, Jiangsu, People’s Republic of China, Email wxf5204079@126.com; hhmmmc@163.comIntroduction: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33– 89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL.Methods: A total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software.Results: We observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74%), MYD88 (50%), KMT2D (38%), KMT2C (34%), BTG2 (34%), TBL1XR1 (34%) and ETV6 (24%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥ 60 years, IPI 3– 5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy.Conclusion: In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.Keywords: primary testicular diffuse large B-cell lymphoma, genetic mutation, BTG2, prognosis, survival

Lu Yu,1 Haiyan Ji,2 Minmin Zhou,1 Yaxin Guo,2 Junfeng Liu,2 Daoyun Lei,3 Chao Han,1 Tieliang Ma1 1Department of Anesthesiology, Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Medical College of Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China; 3Department of Anesthesiology, Zhongda Hospital Southeast University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaCorrespondence: Chao Han, Email staff940@yxph.comBackground: Several studies have shown that ATP-binding cassette transporter A7 (ABCA7) gene variation is associated with cognitive impairment. This study was aimed to investigate the relationship between ABCA7 rs3764650 polymorphism and perioperative neurocognitive disorder (pNCD).Methods: A total of 132 elderly patients aged 65 and over who underwent elective non-cardiac surgery were enrolled in the study, while 28 healthy volunteers matching age and sex were recruited as the control group. A battery of neuropsychological tests was conducted 1 day before, 7 days, and 3 months after surgeries. Delayed neurocognitive recovery (dNCR) and postoperative mild or major neurocognitive disorder (POCD) were determined using the Z value method. The venous blood sample of the surgical patients was taken before the operation. Genotyping of rs3764650 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis.Results: The incidences of dNCR and POCD were 29.7% and 16.8% at 7 days and 3 months after surgery, respectively. The G allele frequency and GG frequency of dNCR patients were significantly higher than that of non-dNCR patients (43.3% vs 28.2%, P=0.035; 23.3% vs 4.2%, P=0.013, respectively) at 7 days following surgery. No significant differences in ABCA7 alleles between POCD and non-POCD patients were observed 3 months postoperatively.Conclusion: ABCA7 rs3764650 gene polymorphism is associated with dNCR and GG genotype might be a predisposing factor for postoperative cognitive impairment in Chinese Han elderly populations.Keywords: ATP-binding cassette transporter, rs3764650, polymorphism, postoperative neurocognitive disorders

Suzhen Chen,1,2 Zhi Xu,1,2 Yinghui Li,1,2 Tianyu Wang,1,2 Yingying Yue,1,2 Zhenghua Hou,1,2 Linlin You,1,2 Na Lu,1,2 Yingying Yin,1,2 Xiaoyun Liu,1,2 Liangliang Tan,1,2 Houcheng Ji,3 Yaoran Shi,1,2 Xiaoyun Xin,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, People’s Republic of ChinaCorrespondence: Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, 210009, People’s Republic of China, Tel +86-25-83285124, Email yygylh2000@sina.comPurpose: Shumian capsule (SMC) is a patent Chinese herbal medicine that can soothe the liver and relieves depression, quiet the spirit. Here, we aimed to investigate the efficacy of SMC for treating insomnia using both scales and polysomnography (PSG).Patients and Methods: A randomized, double-blind, placebo-controlled trial was performed. Twenty-six insomnia patients randomly received SMC (n = 11) or placebo (n = 15) for four weeks. Pittsburgh Sleep Quality Inventory (PSQI), Insomnia Severity Index (ISI), 9-items Patient Health Questionnaire (PHQ-9), 7-items Generalized Anxiety Disorder (GAD-7), 17-item Hamilton Depression Rating Scale (HAMD-17), and Hamilton Anxiety Rating Scale (HAMA) were applied at the baseline and the 2nd, 4th week after treatment. Treatment Emergent Symptom Scale was used to assess adverse reactions. We used PSG to record and analyze sleep features at baseline and after four weeks.Results: PSQI, ISI, PHQ-9, HAMD-17, and HAMA scores decreased significantly after SMC treatment. Also, the total sleep time, rapid-eye-movement (REM) sleep latency, stage 2 sleep, deep sleep, REM sleep, and sleep efficiency improved significantly after SMC treatment. In the placebo group, the only significant change was the decrease of PHQ-9 at week-2. Furthermore, both SMC and placebo reported no adverse events.Conclusion: SMC could safely improve sleep quality with depression and anxiety remission in insomnia patients.Keywords: Chinese herbal medicine, shumian capsule, insomnia, polysomnography, clinical trial, randomized and double-blind method

Lingwei Kong,1,&ast; Yu Wang,1,&ast; Hairu Ji,2 Zhehong Li,1 Yupeng Sun,1 Yanchao Liu,1 Sheng Cao,1 Jingxin Zhao,1 Litao Shi,1 Yu Jin1 1Department of Orthopedics, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, 067000, People’s Republic of China; 2Pathology Teaching and Research Section, Chengde Medical College, Chengde, Hebei, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Jin Tel +86 13832428328Email 358620793@qq.comAbstract: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has received greater attention. It mainly infects diabetic patients and typically causes a hepatic abscess. Here, we report a case of hvKp that caused forearm muscle and soft tissue infection in addition to bacteremia, hepatic and pulmonary abscess, and hyperglycemia. The patient’s condition stabilized after comprehensive treatment. She eventually recovered and was discharged after several debridement and flap operations. At 9 months of follow-up, no signs of infectious recurrence were noted, and the hyperglycemia resolved. Here, we detail important clinical features of a severe hvKp case diagnosed in an otherwise healthy individual. This report underscores the potential of hvKp to cause deep tissue infection and present with clinical symptoms similar to gas gangrene. Symptom onset in the setting of hvKp infection is usually gradual and misdiagnosis is common. The diagnosis of hvKp should be routinely considered in the clinical setting, and be strongly suspected when presenting with characteristic epidemiological, clinical and laboratory features. Although diabetes is a predisposing factor to hvKp infection, hyperglycemia appeared to manifest as a consequence of hvKp infection in this patient.Keywords: hypervirulent K. pneumoniae, hvKp, soft tissue infection, liver abscess, lung abscess, diabetes

Haoqiang Ji,1 Jia Xu,1 Ruiheng Wu,1 Xu Chen,1 Xintong Lv,2 Hongyu Liu,2 Yuxin Duan,1 Meng Sun,1 Yuanping Pan,1 Yunting Chen,1 Xiwei Lu,2 Ling Zhou1 1School of Public Health, Dalian Medical University, Dalian, 116044, People’s Republic of China; 2Office of Epidemic Surveillance, Dalian Tuberculosis Hospital, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Xiwei Lu; Ling Zhou 9 West Section, Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 411 8611 0368Email yiluxiwei@126.com; zhouling0609@163.comPurpose: Despite increasing literature on the association between treatment delay and outcomes, cut-off point (1 month or median) selection in almost all studies for treatment delay is too subjective. This study explored more scientific cut-off points of treatment delay for poor treatment outcomes and death at the clinical level.Patients and Methods: A total of 18,100 newly confirmed pulmonary tuberculosis (TB) cases in Dalian, China were used in the final analysis. A 3-knotted restricted cubic spline (RCS) fitted for Cox proportional hazard regression models is used to analyse the effects of cut-off points of treatment delay on incident poor treatment outcomes. To explore the moderating effects of age, gender and diabetes, we added the interaction terms of these moderating variables and treatment delay to Cox proportional hazard regression models.Results: The median time of treatment initiation was 30 days (IQR: 14– 59 days). The risk of incident poor treatment outcomes increased when the time was greater than cut-off point 1 (53 days; adjusted HR: 1.26; 95% CI: 1.00– 1.60) of treatment delay, and the risk of incident death events increased when the time was greater than cut-off point 2 (103 days; adjusted HR: 1.56; 95% CI: 1.00– 2.44) of delay. In addition, treatment delay was associated with an increased risk of incident poor treatment outcomes and death, and older age, male sex, and diabetes may increase the risk of treatment delay for poor outcomes.Conclusion: This study is the first to identify scientific cut-off points of treatment delay for poor treatment outcomes and death, and this method of exploration should be popularized. In addition, the knowledge of tuberculosis must be spread to every adult. Moreover, the tuberculosis diagnosis level of community level health workers should be enhanced.Keywords: new pulmonary tuberculosis patients, poor treatment outcomes, treatment delay, cut-off points, restricted cubic spline

Li Liu,1,&ast; Tian Xia,2,&ast; Haiyan Ji,1 Yaxin Guo,1 Junfeng Liu,1 Liping Du,1 Daoyun Lei,3 Chao Han,1 Tieliang Ma4 1Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of China; 2Department of Gynaecology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, Zhongda Hospital Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Central Laboratory, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Han Tel +86 0510-87921000 Email staff940@yxph.com.telStudy Objective: To determine whether sub-diaphragmatic irrigation with sodium bicarbonate would relieve post-laparoscopic shoulder pain (PLSP) after total laparoscopic hysterectomy.Design: Randomized double-blinded trial.Setting: Teaching hospital.Patients: Seventy patients undergoing total laparoscopic hysterectomy (TLH) for benign indications.Intervention: We randomly allocated patients to intervention or control groups where sodium bicarbonate containing flushing liquid or normal saline was irrigated sub-diaphragm before sewing.Measurement & Main Results: The primary outcome was PLSP following surgery measured by a numerical rating scale (NRS) (0 = no pain; 10 = worst pain imaginable). Secondary outcomes were abdominal incisional and visceral pain, analgesic use, and sodium bicarbonate related side effects. The incidence of PLSP in intervention group was significantly lower than that in control group (P < 0.05). Contrarily, incisional and visceral pain was similar in both groups (P = 0.1). The consumption of rescue analgesics in the intervention group was lower than that in the control group. Side effects were comparable in both study groups.Conclusion: Sub-diaphragmatic irrigation with sodium bicarbonate could effectively reduce shoulder pain, but not abdominal incisional and visceral pain, in patients undergoing TLH without an increase in side effects.Registration information: Clinical trial registry number: http://www.chictr.org.cn/ (ChiCTR2100041765)Registration findings: http://www.chictr.org.cn/showproj.aspx?proj=66721 Link to clinical trial page and data repository: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=2992Keywords: total laparoscopic hysterectomy, post-laparoscopic shoulder pain, sodium bicarbonate

A 26-year-old woman patient had an 18-year long history of vulvar and vaginal lymphorrhea and multiple millet-like lesions on her vulva. On magnetic resonance image, multiple T2 high signal intensities were noted at the bilateral vulvar areas and pelvic cavity. Conventional lipiodol lymphangiography showed lymphatic reflux to the vulvar areas, possibly originating from prominent tubular lymphatics in the right lower abdominal wall. After percutaneous puncture of this tubular lymphatic structure, its distal portion was embolized using microcoils to prevent upward glue propagation; this was followed by glue embolization of the tubular lymphatic structure. The patient was without skin lesions or symptoms at follow-up of 1 year after the procedure.

Jing Xiong,1,* Yunyun Qian,1,* Shikai Yu,1 HongWei Ji,1 Jiadela Teliewubai,1 Chen Chi,1 YuYan Lu,1 YiWu Zhou,1 XiMin Fan,1 Jue Li,2 Jacques Blacher,3 Yi Zhang,1 YaWei Xu1 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2The Research Institute of Clinical Epidemiology, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Paris Descartes University, AP-HP, Diagnosis and Therapeutic Center, Hôtel-Dieu, Paris, France*These authors contributed equally to this workCorrespondence: Yi Zhang; Yawei XuDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, ChinaTel +86-21-66308182Fax +86-21-66301051Email yizshcn@gmail.com; xuyawei@tongji.edu.cnObjective: To investigate the relationship between asymptomatic target organ damage (TOD) and different somatotypes in a population of elderly from Chinese community-dwelling.Methods: A total of 2098 Chinese senior residents from northern Shanghai older than 65 years were recruited in the research. The following somatotype parameters were recorded and analyzed: body mass index, waist circumference, hip circumference, and waist-hip ratio were recorded and calculated. Asymptomatic TOD, including urine albumin/creatinine ratio, estimated glomerular filtration rate (eGFR), intima-media thickness (IMT), left ventricular mass index (LVMI), left ventricular diastolic function, and carotid-femoral pulse wave velocity (PWV) was recorded using the MyLab30 Gold CV system and SphygmoCor.Results: Of all 2098 residents, 817 (38.9%) were overweight and 289 (13.8%) were obese. All somatotype measures were significantly correlated with TOD parameters (p< 0.05). After adjustment for age and male gender, in total population, LVMI (p< 0.001), cardiac diastolic function (E/Ea, p< 0.001), PWV (p< 0.001), eGFR (p=0.03), and urine albumin/creatinine ratio (p< 0.001) changed gradually and significantly correlated with increasing BMI values. Obesity and overweight were independently related to the incidence of LVH, LVDD, artery stiffness, carotid arterial plaque, and microalbuminuria.Conclusion: The incidence of asymptomatic TOD was significantly correlated with overweight and obesity, especially in women, whereas the underweight may favor in the prevention of TOD.Keywords: Chinese elderly cardiovascular risk

Qing Zhang,1,2 Hong Ji,1,2 Jian Shi,1,2 Longmei Wang,1,2 Lu Ding,1,2 Yufei Jiang,1,2 Xianjing Huang,1,2 Pingping Qiu Snr,1,2 Ping Li1,2 1Department of Reproductive Medicine, Women and Children’s Hospital Affiliated to Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Xiamen Key Laboratory of Reproduction and Genetics, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Pingping Qiu; Ping LiDepartment of Reproductive Medicine, Women and Children’s Hospital Affiliated to Xiamen University, Zhenhai Road 10, Xiamen, Fujian, 361003, People’s Republic of ChinaTel +86-592-2663987Fax +86-592-2662032Email Pingingqiu826@163.com; saarc2001@sina.comPurpose: The ratio of mitochondrial DNA to genomic DNA (mtDNA/gDNA) in embryo culture medium as a predictor of embryonic development is a new method of noninvasive embryo screening. However, current tests based on this concept have proven inconsistent. The aim of this study was to define the predictive value of the ratio of mtDNA/gDNA for embryonic developmental potential.Materials and Methods: We used digital PCR to measure mtDNA/gDNA ratios in day 3 culture media of 223 embryos from 56 patients. We compared the relationship between the predictive value of mtDNA/gDNA ratio and each of embryo fragmentation, embryo morphological grade, and blastocyst formation.Results: mtDNA/gDNA ratio decreased significantly with a decrease in embryo rating: 22.54 (44.66); 31.25 (36.97) and 46.33 (57.11); Grades A vs C, P = 0.006; B vs C, P = 0.015. mtDNA/gDNA ratio increased overall with an increase in embryo fragment content but did not differ significantly between high-, -medium, and poor-quality embryos. Interestingly, this trend differed from that of the unformed blastocysts. mtDNA/gDNA ratio of cleavage stage embryos forming blastocysts was lower (P=0.005). Trends of mtDNA/gDNA ratio differed according to inner cell mass (ICM) and trophectoderm (TE) levels, but not significantly. mtDNA/gDNA ratio in day 3 culture medium was not significantly improved over morphological scores.Conclusion: We hereby show the correlation of mtDNA/gDNA ratio in the culture medium of developing embryos. The correlation between the mtDNA/gDNA ratio and early embryonic development was controversial. Furthermore, an increase in mtDNA/gDNA ratio might indicate reduced development potential, but the difference remains insufficient for application as a clinical predictor.Keywords: mtDNA/gDNA, embryo, digital PCR, blastocyst

Liang Du,1 Yu Zhang,1 Xintong Lv,2 Yuxin Duan,1 Xiaoyan Shi,2 Haoqiang Ji,1 Ruiheng Wu,1 Jia Xu,1 Xu Chen,1 Yang Gao,2 Xiwei Lu,2 Ling Zhou1 1School of Public Health, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 2Dalian Tuberculosis Hospital, Dalian, Liaoning, 116031, People’s Republic of ChinaCorrespondence: Xiwei Lu; Ling Zhou 9 West Section, Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 411 8611 0368Email tb_luxiwei@126.com; zhouling0609@163.comPurpose: Multidrug-resistant tuberculosis (MDR-TB) is the cause of serious health and economic burdens worldwide. The present study aimed to explore the initial and acquired drug-resistance rates among TB patients from 2012 to 2019 in Dalian, China. The effectiveness of MDR-TB prevention and control strategies were then evaluated.Patients and Methods: Drug susceptibility testing (DST) was performed for 6429 diagnosed, culture-positive, Mycobacterium tuberculosis (MTB) strains, including 4661 new cases and 1768 previously treated cases. Descriptive statistics were employed to calculate the frequencies and percentages of TB strains, and the average annual growth rates (AAGRs) for each strain were calculated. The Chi-square test was applied to examine the significance of linear drug-resistance trends over time during the study period.Results: Over the eight-year study period, the percentages of both initial (from 9.01% to 4.82%) and acquired (from 40.85% to 9.09%) MDR-TB cases decreased significantly, AAGRs of 8.55% and 19.32%, respectively. Among new and previously treated TB patients, significant downtrends were observed for the rates of both initial and acquired MDR-TB among young and middle-aged individuals (P < 0.05). Additionally, among both new and previously treated TB patients, the percentages of individuals with drug resistance against isoniazid (INH), rifampicin (RFP), ofloxacin (OFX), and amikacin (AMK) decreased significantly (P < 0.05) from 2012 to 2019 in Dalian, China.Conclusion: The initial and acquired multidrug resistance rates exhibited significantly decreasing trends from 2012 to 2019, suggesting that MDR-TB prevalence has been controlled effectively in Dalian, China. The MDR-TB epidemic was reversed in the short term by establishing feasible strategies for detection, diagnosis, treatment, and infection control.Keywords: TB, initial, acquired, MDR, epidemic

Pengchong Wang,1,2 Yan Yan,1,2 Ying Zhang,2 Tingting Gao,2 Hongrui Ji,2 Shiyan Guo,2 Ke Wang,2 Jianfeng Xing,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Yalin Dong; Jianfeng Xing Email dongyalin@mail.xjtu.edu.cn; xajdxjf@mail.xjtu.edu.cnBackground: Carbon dots (CDs) emitting near-infrared fluorescence were recently synthesized from green leaves. However, the Hg2+ detection of CDs was limited because of the insufficient water solubility, low fluorescence and poor stability.Methods: Dual fluorescence emission water-soluble CD (Dual-CD) was prepared through a solvothermal method from holly leaves and low toxic PEI1.8k. PEG was further grafted onto the surface to improve the water solubility and stability.Results: The Dual-CD solution can emit 487 nm and 676 nm fluorescence under single excitation and exhibit high quantum yield of 16.8%. The fluorescence at 678 nm decreased remarkably while the emission at 470 nm was slightly affected by the addition of Hg2+. The ratiometric Hg2+ detection had a wide linear range of 0– 100 μM and low detection limit of 14.0 nM. In A549 cells, there was a good linear relation between F487/F676 and the concentration of Hg2+ in the range of 0– 60 μM; the detection limit was 477 nM. Furthermore, Dual-CD showed visual fluorescence change under Hg2+.Conclusion: Dual-CD has ratiometric responsiveness to Hg2+ and can be applied for quantitative Hg2+ detection in living cells.Keywords: chlorophyll, polyethyleneimine, polyethylene glycol, ratiometric Hg2+ detection, A549 cells

Xiaoliang Sun, Jun Liu, Haoyang Ji, Meng Yang, Yao Lu Department of General Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yao LuDepartment of General Surgery, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of ChinaEmail zrluyao@163.comObjective: Breast cancer (BC) in young women tends to be more aggressive. This study highlights the clinicopathological features and outcomes of young breast cancer (YBC) patients in a developing country.Methods: Consecutive patients aged 35 years or younger with a pathologically confirmed diagnosis of breast cancer treated and followed up at our department were included. Medical records and follow-up databases were reviewed and documented.Results: The rate of breast conservation and reconstruction surgery is higher in YBC patients. YBC patients are more likely to have tumors over 5cm, high-grade, hormone receptor negative, triple negative and stage III than old patients. There was no statistically significant difference in the pathological type, lymph node metastasis, and HER2 status. The median follow-up time was 96 months. The disease-free survival (DFS) was significantly worse in the YBC group. However, the overall survival (OS) had no difference between the two groups.Conclusion: YBC patients had more aggressive pathological features, such as hormone receptor negative, triple negative, high-grade and advanced stage, and poorer DFS than the old counterparts.Keywords: young age, breast cancer, clinicopathological characteristics, survival, molecular subtypes

Runan Zuo,1 Jingjing Zhang,1 Xinhao Song,1 Shiheng Hu,1 Xiuge Gao,1 Junqi Wang,1 Hui Ji,1 Chunlei Ji,1 Lin Peng,1 Hongbin Si,2 Gonghe Li,2 Kun Fang,3 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2College of Animal Science and Technology, Guangxi University, Nanning, 530004, People’s Republic of China; 3Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang JiangCenter for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of ChinaTel + 86-25-84396215Fax + 86-25-84398669Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone hydrobromide (HF) is a synthetic analogue of the naturally occurring quinazolinone alkaloid febrifugine, which has potential therapeutic effects against breast cancer, however, its poor water solubility greatly limits its pharmaceutical application. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E, which can self-assemble to form polymeric micelles (PMs) for encapsulating insoluble anti-tumor drugs, thereby effectively enhancing their anti-cancer effects.Methods: HF-loaded TPGS PMs (HTPMs) were manufactured using a thin-film hydration technique, followed by a series of characterizations, including the hydrodynamic diameter (HD), zeta potential (ZP), stability, drug loading (DL), encapsulation efficiency (EE), and in vitro drug release. The anti-cancer effects and potential mechanism of HTPMs were investigated in the breast cell lines MDA-MB-231 and MCF-7, and normal breast epithelial cell line Eph-ev. The breast cancer-bearing BALB/c nude mouse model was successfully established by subcutaneous injection of MDA-MB-231 cells and used to evaluate the in vivo therapeutic effect and safety of the HTPMs.Results: The optimized HTPMs had an HD of 17.8± 0.5 nm and ZP of 14.40± 0.1 mV. These PMs exhibited DL of 12.94 ± 0.46% and EE of 90.6 ± 0.85%, along with excellent storage stability, dilution tolerance and sustained drug release in pH-dependent manner within 24 h compared to free HF. Additionally, the HTPMs had stronger inhibitory effects than free HF and paclitaxel against MDA-MB-231 triple-negative breast cancer cells, and little toxicity in normal breast epithelial Eph-ev cells. The HTPMs induced cell cycle arrest and apoptosis of MDA-MB-231 by disrupting the mitochondrial membrane potential and enhancing reactive oxygen species formation. Evaluation of in vivo anti-tumor efficacy demonstrated that HTPMs exerted a stronger tumor inhibition rate (68.17%) than free HF, and exhibited excellent biocompatibility.Conclusion: The findings from this study indicate that HTPMs holds great clinical potential for treating triple-negative breast cancer.Keywords: halofuginone hydrobromide, triple-negative breast cancer, TPGS, polymer micelles

Hongfei Xu,1,* Hongyu Ji,1,2,* Zerong Li,1,3 Wenmei Qiao,1,4 Chenghao Wang,1 Jingling Tang1 1Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, People’s Republic of China; 3Department of Pharmacy, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518028, People’s Republic of China; 4Department of Pharmacy, Shenzhen Luohu Hospital Group-Shenzhen Luohu Traditional Chinese Medicine Hospital, Shanghai University of Traditional Chinese Medicine-Shenzhen Hospital, Shenzhen, 518001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingling TangDepartment of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, People’s Republic of ChinaTel +86-0451-86660103Fax +86-0451-86664073Email tangjl430@hotmail.comBackground: Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells and causes occlusion of pulmonary arterioles that eventually results in right heart failure and death. The platelet-derived growth factor (PDGF) plays a prominent role in abnormal remodeling of pulmonary resistance vessels. Imatinib mesylate (IM), a PDGF-receptor tyrosine kinase inhibitor, was able to ameliorate PAH by reversing pulmonary vascular remodeling.Methods: In the present study, IM-loaded liposomes (IM-LPs) were developed and administered via the pulmonary route to delay the drug release and improve patient compliance for the treatment of PAH. The IM-LPs were prepared by the transmembrane gradient method with the spherical vesicles. The compatibility of the IM-LPs was studied by determining the viability of pulmonary arterial smooth muscle cells (PASMCs). Particle uptake by rat PASMCs was evaluated by incubating the particles with rat PASMCs. Pharmacokinetic studies were performed in male SD rats.Results: The IM-LPs showed an average size of 101.6 ± 50.80 nm with a zeta potential value of 19.66 ± 0.55 mV, a PDI of 0.250 and 81.96% ± 0.98% drug entrapment efficiency, meanwhile displayed a sustained release profile. Liposomes obviously increased intracellular accumulation of Rhodamine B by PASMCs using the fluorescence microscopic. Following intratracheal administration to rats, IM-LPs not only extended the half-life of IM, but also prolonged retention of IM compared with plain IM solution after intratracheal and intravenous administration.Conclusion: The study show potential applications of the LPs for pulmonary delivery of IM and the method for the development of LPs in sustained release of IM for better therapeutic outcomes. Conclusively, the prepared IM-LPs were well designed in nanosized ranges and may be a promising formulation for pulmonary delivery of IM.Keywords: imatinib mesylate, pulmonary arterial hypertension, liposomes, pulmonary delivery, pharmacokinetics

Guoming Zeng,1,2,* Libo Jin,3,4,* Qinsi Ying,5 Haojie Chen,3 Murinda Charmaine Thembinkosi,3 Chunguang Yang,6 Jinlong Zhao,6 Hao Ji,3 Sue Lin,3 Renyi Peng,3 Maolan Zhang,1,3 Da Sun3 1Chongqing University of Science and Technology, Chongqing 401331, People’s Republic of China; 2China Metallurgical Construction Engineering Group Co., Ltd., Chongqing 400044, People’s Republic of China; 3Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, People’s Republic of China; 4Biomedical Collaborative Innovation Center of Zhejiang Province & Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou, Zhejiang 325035, People’s Republic of China; 5Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325035, People’s Republic of China; 6Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Da SunInstitute of Life Sciences, Wenzhou University, Higher Educational Park, Wenzhou City 325035, Zhejiang Province, People’s Republic of ChinaEmail sunday@wzu.edu.cnMaolan ZhangChongqing University of Science and Technology, No. 19, Xijiao Branch Road, Jiulongpo District, Chongqing 400050, People’s Republic of ChinaEmail zml@cqu.edu.cnAbstract: Cancer immunotherapy is a promising approach that has recently gained its importance in treating cancer. Despite various approaches of immunotherapies being used to target cancer cells, they are either not effective against all types of cancer or for all patients. Although efforts are being made to improve the cancer immunotherapy in all possible ways, one important hindrance that lowers the immune response to kill cancer cells is the infiltration of Regulatory T (Treg) cells into the tumor cells, favoring tumor progression, on one hand, and inhibiting the activation of T cells to respond to cancer cells, on the other hand. Therefore, new anti-cancer drugs and vaccines fail to show promising results against cancer. This is due to the infiltration of Treg cells into the tumor region and suppression of anti-cancer activity. Thus, regardless of various types of immunotherapies being practiced, understanding the mechanisms of how Treg cells favor tumor progression and inhibition of anti-cancer activity is worthwhile. Therefore, the review highlights the importance of Tregs cells and how depletion of Treg cells can pave the way to an effective immunotherapy by activating the immune responses against cancer.Keywords: cancer immunotherapy, Treg cells, FoxP3, targeting Treg cells, anti-cancer

Miscanthus is a perennial grass with potential for lignocellulosic ethanol production. To ensure its utility for this purpose, breeding efforts should focus on increasing genetic diversity of the nothospecies Miscanthus × giganteus (M×g) beyond the single clone used in many programs. Germplasm from the corresponding parental species M. sinensis (Msi) and M. sacchariflorus (Msa) could theoretically be used as training sets for genomic prediction of M×g clones with optimal genomic estimated breeding values for biofuel traits. To this end, we first showed that subpopulation structure makes a substantial contribution to the genomic selection (GS) prediction accuracies within a 538-member diversity panel of predominately Msi individuals and a 598-member diversity panels of Msa individuals. We then assessed the ability of these two diversity panels to train GS models that predict breeding values in an interspecific diploid 216-member M×g F2 panel. Low and negative prediction accuracies were observed when various subsets of the two diversity panels were used to train these GS models. To overcome the drawback of having only one interspecific M×g F2 panel available, we also evaluated prediction accuracies for traits simulated in 50 simulated interspecific M×g F2 panels derived from different sets of Msi and diploid Msa parents. The results revealed that genetic architectures with common causal mutations across Msi and Msa yielded the highest prediction accuracies. Ultimately, these results suggest that the ideal training set should contain the same causal mutations segregating within interspecific M×g populations, and thus efforts should be undertaken to ensure that individuals in the training and validation sets are as closely related as possible.

Liang Du,1 Xu Chen,1 Xuexue Zhu,1 Yu Zhang,1 Ruiheng Wu,1 Jia Xu,1 Haoqiang Ji,1 Ling Zhou,1 Xiwei Lu2 1School of Public Health, Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of China; 2Department of Tuberculosis Internal Medicine, Dalian Tuberculosis Hospital, Dalian, Liaoning 116031, People’s Republic of ChinaCorrespondence: Ling Zhou; Xiwei Lu Tel +86-411-8611-0368Email zhouling0609@163.com; tb_luxiwei@126.comPurpose: Medication adherence is crucial for decreasing the burden of tuberculosis, but few relevant studies have been conducted in northeast China. This study aimed to explore the level of medication adherence among pulmonary tuberculosis outpatients and the predictive factors based on the bio-psycho-social medical model.Patients and Methods: A cross-sectional multi-center survey was conducted in four tuberculosis medical institutions in Dalian, northeast China. Medication adherence was measured using the eight-item Chinese version of the Morisky Medication Adherence Scale, which divides adherence into three levels. The independent variables consisted of sociodemographic characteristics, treatment factors, knowledge about TB, mental health, and behavioral characteristics. Descriptive statistics, the chi-square test, and multivariate ordinal logistic regression were applied to analyze the data using Stata/MP 14.0.Results: Among the 564 eligible participants, 236 (41.84%) and 183 (32.45%) exhibited high and medium medication adherence, respectively, but 145 (25.71%) exhibited low medication adherence. Multivariate ordinal logistic regression showed that patients who were older (OR: 1.02, p=0.013) were employed (OR: 1.61, p=0.011), had better tuberculosis knowledge (OR: 1.34, p< 0.001), and did not consume alcohol (OR: 1.84, p=0.032) exhibited higher medication adherence. However, patients who did not follow their doctors’ advice to take adjuvant drugs (OR: 0.44, p=0.001), had a history of TB treatment (OR: 1.76, p=0.009), experienced adverse drug reactions (OR: 0.65, p=0.017), experienced stigma (OR: 0.67, p=0.032), and needed supervised treatment (OR: 0.66, p=0.012) exhibited lower medication adherence.Conclusion: Tuberculosis patients’ medication adherence was not very high and it was influenced by diverse and complex factors involving sociodemographic characteristics, treatment factors, knowledge about TB, mental health, and behavioral characteristics.Keywords: tuberculosis patients, treatment, influence factors, bio-psycho-social medical model, Chinese context

Abstract Background Inanimate surfaces within a hospital serve as a reservoir of microbial life that may colonize patients and ultimately result in healthcare associated infections (HAIs). Critically ill patients in intensive care units (ICUs) are particularly vulnerable to HAIs. Little is known about how the microbiome of the ICU is established or what factors influence its evolution over time. A unique opportunity to bridge the knowledge gap into how the ICU microbiome evolves emerged in our health system, where we were able to characterize microbial communities in an established hospital ICU prior to closing for renovations, during renovations, and then after re-opening. Results We collected swab specimens from ICU bedrails, computer keyboards, and sinks longitudinally at each renovation stage, and analyzed the bacterial compositions on these surfaces by 16S rRNA gene sequencing. Specimens collected before ICU closure had the greatest alpha diversity, while specimens collected after the ICU had been closed for over 300 days had the least. We sampled the ICU during the 45 days after re-opening; however, within that time frame, the alpha diversity never reached pre-closure levels. There were clear and significant differences in microbiota compositions at each renovation stage, which was driven by environmental bacteria after closure and human-associated bacteria after re-opening and before closure. Conclusions Overall, we identified significant differences in microbiota diversity and community composition at each renovation stage. These data help to decipher the evolution of the microbiome in the most critical part of the hospital and demonstrate the significant impacts that microbiota from patients and staff have on the evolution of ICU surfaces. Video Abstract

Objective: To determine whether a single-use stethoscope diaphragm barrier surface remains aseptic when placed on pathogen-contaminated stethoscopes. Methods: From May 31 to August 5, 2019, we tested 2 separate barriers using 3 different strains of 7 human pathogens, including extended-spectrum β-lactamase–producing Escherichia coli, methicillin-resistant Staphylococcus aureus, and vancomycin resistant Enterococcus faecium. Results: For all diaphragms with either of the 2 barriers tested, no growth was recorded for any of the pathogens. Stethoscopes with aseptic barriers remained sterile for up to 24 hours. These single-use barriers also provided aseptic surfaces when stethoscope diaphragms were inoculated with human specimens, including saliva, stool, urine, and sputum. Conclusion: Disposable aseptic diaphragm barriers may provide robust and efficient solutions to reduce transmission of pathogens via stethoscopes.

Xuan Zhou, 1,* Huihui Ji, 2,* Dongxue Ye, 2 Hong Li, 1 Fen Liu, 2 Haiyan Li, 2 Jin Xu, 1 Yujun Li, 1 Fenggang Xiang 1, 2 1Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 2Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fenggang XiangDepartment of Pathology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266000, People’s Republic of ChinaEmail xiangfenggang0532@163.comIntroduction: The aim of the present study was to examine the expression of ATAD2 in gastric cancer (GC) specimens and to evaluate its correlation with clinicopathologic features, including survival of GC patients. The potential roles of ATAD2 in the GC cell proliferation, apoptosis, and tumour growth were further explored.Materials and Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were applied to determine the mRNA and protein expression of ATAD2 in GC and corresponding adjacent non-tumourous specimens. The relationship between ATAD2 expression and clinicopathological features of GC patients was analysed. Kaplan-Meier analysis was performed to assess the prognostic value of ATAD2 expression levels. The proliferation, colony formation, apoptosis and tumorigenesis roles of ATAD2 were measured using in vitro and in vivo experiments.Results: The expression of ATAD2 mRNA and protein was overexpressed in GC tissues compared with corresponding adjacent non-tumourous tissues. ATAD2 expression was significantly correlated with tumour size, tumour differentiation, and clinical tumour-node-metastasis (TNM) stage. Patients with high ATAD2 expression were likely to experience significantly shorter postoperative overall survival (OS) and disease-free survival (DFS). Multivariate Cox analysis suggested ATAD2 as an independent variable for OS and DFS. Knockdown of ATAD2 significantly suppressed cell proliferation, colony formation in vitro and tumorigenicity in vivo. Cell cycle and apoptotic assays showed that the anti-proliferative effect of pLV-ATAD2 shRNA was mediated by arresting cells in the G1 phase and inducing cell apoptosis. Silencing of ATAD2 reduced the expression of cyclinD1, ppRb, E2F1 and cyclinE and upregulated the expression of cleaved-PARP and cleaved-Caspase 3.Conclusion: Our study indicated that ATAD2 plays an important role in the process of tumorigenesis and progression in GC, and it could serve as a novel prognostic biomarker and a therapeutic target for the treatment of GC patients.Keywords: ATAD2, gastric cancer, proliferation, apoptosis, prognosis

H2 permeation in peroxide-crosslinked EPDM blended with carbon black (CB) and silica fillers was studied at pressures ranging from 1.2 MPa to 90 MPa via the volumetric analysis technique. H2 uptake in the CB-filled EPDM revealed dual-sorption behaviors via Henry’s law and the Langmuir model, which were attributed to H2 absorption by the polymer chains and H2 adsorption at the filler interfaces, respectively. Additionally, single-sorption mechanisms were observed for neat EPDM and silica-blended EPDM according to Henry’s law, indicating H2 absorption by the polymer chain. The linear decreases in the diffusivity with filler content for the silica-blended EPDMs were attributed to increases in the diffusion paths caused by the filler. Exponential decreases in the diffusivity with increasing filler content and in the permeation with the physical/mechanical properties for CB-filled EPDMs were caused by decreases in the fractional free volume due to increased densities for the EPDM composites. Moreover, good filler-dependent correlations between permeability and density, hardness, and tensile strength were demonstrated for EPDMs used as sealing materials for O-rings. From the resulting equation, we predicted the permeation value without further measurements. Thus, we can select EPDM candidates satisfying the permeation guidelines used in hydrogen infrastructure for the future hydrogen economy.

Rationale: Cell-based therapeutics have been extensively used for cardiac repair yet underperform due to inability of the donated cells to survive in near anoxia after cardiac injury. Cellular metabolism is linked to maintenance of cardiac stem cell (CSC) renewal, proliferation and survival. Ex vivo expansion alters (CSC) metabolism increasing reliance on oxygen dependent respiration. Whether promoting ‘metabolic flexibility’ in CSCs augments their ability to survive in near anoxia and repair the heart after injury remains untested. Objective: Determine the effect of LIN28a induced metabolic flexibility on cardiac tissue derived stem like cell (CTSC) survival and repair after cardiac injury. Methods and results: LIN28a expression coincides during heart development but is lost in adult CTSCs. Reintroduction of LIN28a in adult CTSC (CTSC-LIN) increased proliferation, survival, expression of pluripotency genes and reduced senescence compared to control (CTSC-GFP). Metabolomic analysis show glycolytic intermediates upregulated in CTSC-LIN together with increased lactate production, pyruvate kinase activity, glucose uptake, ECAR and expression of glycolytic enzymes compared to CTSC-GFP. Additionally, CTSC-LIN showed significantly reduced ROS generation and increase antioxidant markers. In response to H2O2 induced oxidative stress, CTSC-LIN showed increased survival and expression of glycolytic genes. LIN28a salutary effects on CTSCs were linked to PDK1/let-7 signaling pathway with loss of PDK1 or alteration of let-7 abrogating LIN28a effects. Following transplantation in the heart after myocardial infarction (MI), CTSC-LIN showed 6% survival rate at day 7 after injection compared to control cells together with increased proliferation and significant increase in cardiac structure and function 8 weeks after MI. Finally, CSTC-LIN showed enhanced ability to secrete paracrine factors under hypoxic conditions and ability to promote cardiomyocyte proliferation following ischemic cardiac injury. Conclusions: LIN28a modification promotes metabolic flexibility in CTSCs enhancing proliferation and survival post transplantation including ability to repair the heart after myocardial injury.

Ming Zhao, Ji Li, Hongrui Ji, Dawei Chen, Haiyang HuDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaBackground: Polycation carriers show great foreground in the developing efficient and safe gene delivery; nevertheless, they are cytotoxic and unstable in vivo because of the excess cationic charge. PEGylation improves the biocompatibility and stability of polycation, whereas PEGylation restrains the endosomal escape to some extent.Materials and methods: To address this issue and promote the transfection in vivo, a pH-sensitive conjugate folate-polyethylene glycol-carboxylated chitosan (shorten as FA-PEG-CCTS) was designed and coated on the surface of PEI/NLS/pDNA (PNDs), forming a versatile gene carrier FA-PEG-CCTS/PEI/NLS/pDNA (FPCPNDs). The novel carrier exhibited a few picturesque characteristics, including (i) neutral surface charge to restrain nonspecific interactions; (ii) folate receptors (FR)-mediated endocytosis to augment cellular uptake; (iii) dual proton sponge effect to realize endosome escape, and (iv) nuclear localization sequences (NLS) to enhance the transfection of pDNA.Results: FPCPNDs could compress and protect pDNA from degradation. FPCPNDs energetically targeted tumor cells because of their high binding affinity between FA and highly expressed FR on the tumor surface, accordingly enhancing the cellular uptake. In the acidic endosomes, FA-PEG-CCTS segment dissociated from PNDs. Then, PNDs realized endosomal escape through the proton sponge effect of PEI. Furthermore, FPCPNDs showed admirable transfection efficiency with the aid of NLS peptides. What’s more, in vivo studies revealed that FPCPNDs had supreme antitumor activity among the whole preparations.Conclusion: In vitro and in vivo assays thus demonstrate that FPCPNDs is a hopeful strategy for gene delivery.Keywords: gene delivery, PEI, gene transfection, NLS, shell–core structure, CCTS

Qijia Xuan,1,* Yan Yang,1,* Hongfei Ji,2 Shuli Tang,1 Juan Zhao,1 Jiayue Shao,1 Jingxuan Wang11Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province 150081, People’s Republic of China; 2Department of Cancer Molecular and Biology, Cancer Institute, Harbin Medical University, Harbin, Heilongjiang Province 150081, People’s Republic of China*These authors contributed equally to this work Background: The pretreatment albumin to globulin ratio (AGR) and neutrophil to lymphocyte ratio (NLR) were the inflammation-associated factors which were related to the disease-free survival in various malignancies. The aim of this study was to evaluate the clinical significance of the pretreatment AGR combined with NLR for patients with triple negative breast cancer (TNBC).Method: This retrospective study included 286 cases of pathologically diagnosed patients with TNBC. The relationships of AGR and NLR with clinicopathologic characteristics and prognosis were analyzed by Kaplan–Meier and Cox regression methods.Results: An AGR of 1.63 and a NLR of 2.93 were identified as the optimal cut-off points for distinguishing patients with good versus poor prognosis. The area under the receiver operating characteristic curves of combined with AGR and NLR (CO-AN) was increased compared with AGR and NLR individually. Kaplan–Meier analysis showed that low AGR/high NLR was related to poor survival. The prognosis of patients can be predicted well by the CO-AN. Univariate and multivariate analyses revealed that high AGR levels, low NLR levels, and CO-AN

Shu Zhao,1,* Mengqi Sun,1,* Hongxue Meng,2 Hongfei Ji,3 Yupeng Liu,4 Minghui Zhang,1 Hongbin Li,1 Pengfei Li,5 Yue Zhang,1 Qingyuan Zhang11Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China; 2Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China; 3Heilongjiang Cancer Research and Prevention Institute, Harbin, Heilongjiang, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Medical Imaging Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workBackground: Toll-like receptor 4 (TLR4), a member of the pattern recognition receptors, has been reported to be involved in carcinogenesis. However, the clinical impact of TLR4 in peripheral T-cell lymphomas (PTCL) remains unclear.Methods: The current study, using immunohistochemical staining, first examined TLR4 and programmed cell death-ligand 1 (PD-L1) expression in patients with PTCL, to correlate TLR4 and PD-L1 expression with clinicopathological parameters.Results: It was found that the rates of high expression of TLR4 and PD-L1 were 41.7% and 45.8%, respectively. TLR4 expression was closely associated with PD-L1 expression. The expression of TLR4 was closely related to primary extranodal site involvement, increased Ann Arbor stage, and low hemoglobin expression, while the expression of PD-L1 was closely related to a low platelet count and multiple extranodal organ involvements (>1). High expression of either TLR4 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analyses further confirmed that increased expression levels of TLR4 and PD-L1 are unfavorable prognostic factors for PTCL.Conclusion: This study demonstrates that the expressions of TLR4 and PD-L1 are independent predictors of survival time for patients with PTCL. Thus, TLR4 and PD-L1 may serve as potential therapeutic targets in PTCL patients.Keywords: TLR4, PD-L1, peripheral T-cell lymphomas, non-Hodgkin’s lymphoma, immune checkpoint inhibitor, survival

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.

Cytokine signaling in the epidermis has an important role in maintaining barrier function and is perturbed in pathological conditions. Environmental exposures, such as to metal compounds, are of interest for their potential contribution to skin disease. Present work explores the possibility that vanadate is a more effective protein tyrosine phosphatase inhibitor in human keratinocytes than previously observed in fibroblasts. It focuses on the state of phosphorylation of signal transducer and activator of transcription 1 (STAT1) on tyrosine 701 upon treatment of cultured human keratinocytes with the cytokine oncostatin M, a cutaneous inflammatory mediator that is highly effective in suppressing several differentiation markers and in preserving proliferative potential of keratinocytes. Exposure to sodium vanadate in the medium greatly prolonged the phosphorylation of STAT1, but only at high concentration (>30 µM). Inhibitors of protein tyrosine phosphatases known to dephosphorylate STAT1 (SHP2, TCPTP, PTP1B) were ineffective in mimicking the action of vanadate. The irreversible protein tyrosine phosphatase inhibitor phenyl vinyl sulfonate alone induced STAT1 phosphorylation and appeared to induce its limited cleavage. It also inhibited cross-linked envelope formation, a characteristic step of keratinocyte terminal differentiation, likely due to its reaction with the active site cysteine of keratinocyte transglutaminase. Thus, the key protein tyrosine phosphatase responsible for STAT1 dephosphorylation remains to be identified, and an off-target effect of a potential inhibitor was revealed.

Guoxiang Liu, Qifeng Yin, Huanhuan Ji, Yujuan Wang, Huihui Liu, Liangqian Jiang, Feng Zhu, Bing Li Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao 266071, People’s Republic of China Background: To improve the targeting ability of antitumor drugs, we identified the antigens with high expression on the surface of tumor cells associated with tumor escape, such as the complement regulatory protein CD55 molecule, which is also known as the decay accelerating factor. In this study, phage display technology was used to screen and identify CD55-specific ligand peptide (CD55sp) bound to CD55 molecule on the surface of cervical cancer HeLa cells. We then explored the role of this peptide in inhibiting the growth of cervical cancer cells in vitro. Our characterization of CD55sp will provide implication for tumor target therapy. Methods: The phage bound to the surface of HeLa cells were isolated by phage display technology. Positive phage clones were identified by ELISA. Phage was then amplified and determined by agarose gel electrophoresis after monoclonal DNA extraction. DNA sequencing and bioinformatical analysis were conducted to obtain specific ligand peptides. Flow cytometry and immunofluorescence were used to measure the expression of CD55 molecule on the surface of tumor and normal cells. Subsequently, the effects of CD55sp on the proliferation and apoptosis of HeLa and SiHa cells were determined by Cell Counting Kit-8 (CCK-8), flow cytometry, and TUNEL assay, respectively. The morphology of apoptotic cells was examined by electron microscope. The distribution of Cleaved caspase-3 was detected by immunofluorescence. The expression of bcl-2 and Cleaved caspase-3 were determined by Western blot. Results: The results showed that the peptide (QVNGLGERSQQM) can bind to the CD55 molecule on the surface of cervical cancer HeLa and SiHa cells as a ligand peptide. It can also effectively inhibit the proliferation of cervical cancer cells and induce cell apoptosis. Conclusion: This study demonstrates that CD55sp screened by phage display technology plays a strong antitumor role. Keywords: phage display, cervical cancer, CD55sp, ligand peptide, apoptosis

ABSTRACT Objective To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. Subjects and methods Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). Results 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. Conclusion 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.