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Background and objectives Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Disulfiram (DSF), as an anti-alcoholic drug, kills the cancer cells by inducing apoptosis. Several preclinical and clinical studies have examined the potential of repurposing DSF as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans. Methods Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics. Results Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates, separately. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule. There was no noticeable body weight loss after DSF treatment, which indicated that there was no major toxicity of DSF. Conclusions This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.

The surgical management of large or giant prostate still has challenges to urologists, especially if combined with bladder stones, and the traditional techniques by open prostatectomy and cystolithotomy have significant morbidity rates. The endoscopic procedure might not be feasible to treat both conditions in a single procedure, despite advances in surgical techniques and instrumentation, we present a one-session procedure by a combined endoscopic and open approach for treating benign prostatic hyperplasia (BPH) larger than 100 g combined with bladder stones in the elderly patient with other comorbidities. Between May 2017 and January 2020, bipolar transurethral plasma kinetic enucleation of the prostate (TUEP) followed by open cystolithotomy was performed to six patients at our institution, three of them combined with a big bladder stone(s). All the patients have other chronic chest and heart diseases; we retrospectively collected the data. All the patients diagnosed as BPH of big size or giant prostate over 100 g, with bladder stone, and all the patients treated with the same procedure. We founded that the combination methods showed a significant effect in terms of surgery time, patient outcomes and recovery, hospital discharge. The mean age of patients was 78.16 ± 4.2 (73–84) years, and the mean prostate-specific antigen (PSA) value was 16.27 ± 10.01 (8.32–32.17) ng/mL. The mean size of the prostate measured by MRI/US was 266.16 ± 89.1 (169–405) mL. The mean total operation time was 70.5 ± 10.9 (60–90) min, while the mean enucleation time was 28.38 ± 6.61 (23–40) min. The mean intraoperative blood loss was 193.33 ± 19.66 (170–220) mL. The mean resected prostate weight was 217.166 ± 94.67 (117–365) g. The mean post-operative hospital stay was 2.6 ± 0.81 (2–4) days. One patient was readmitted 2 months later due to urinary tract infection, and one patient complains of urine incontinence who spontaneously subsided in 4 months after surgery, other that no severe postoperative complications observed, a significant reduction of serum PSA and IPSS recorded at 3 months, postoperatively. Although simple open prostatectomy remains the reference standard for the treatment. Of excessively large or giant prostatic hyperplasia, the combination procedure not only facilitates the management of selected cases of hyperplasia but further imparts significant benefits to patients and surgeons alike. This treatment plan is safe, time-consuming, and could revolutionize future treatment approaches to giant prostate.

Purpose. To investigate the vascular density of the optic nerve head (ONH) and macula using optical coherence tomography angiography (OCTA) in patients undergoing vitrectomy for rhegmatogenous retinal detachment (RRD) and to evaluate associations with visual outcomes. Methods. Patients with RRD, successfully treated with a pars plana vitrectomy (PPV) and a minimum three-month follow-up were included in this study. The vessel density (VD) of the ONH and peripapillary regions, foveal avascular zone (FAZ), foveal flow density (FFD), and parafoveal flow density (PFD) were evaluated using OCTA and compared to the fellow eye. Multivariate linear regression analysis was performed to determine correlations with visual outcomes. Results. Thirty-one patients with macula-off RRD were included in the study. Compared with the fellow eyes, eyes after RRD surgery had a lower peripapillary VD ( P < 0.01 ). No significant difference in superficial and deep FFD, PFD, and FAZ area was found compared to the fellow eyes. Postoperative peripapillary VD and baseline BCVA were significantly associated with BCVA three months after PPV ( P < 0.05 ). Conclusion. Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower peripapillary vessel density than fellow healthy eyes. Postoperative BCVA was related to postoperative peripapillary VD.

A newly discovered natural hybrid, Iris × ampliflora Y.E. Xiao, F.Y. Yu & X.F. Chen (Iridaceae: subgenus Limniris section Lophiris) from Chongqing, China, is described and illustrated. This hybrid is morphologically similar to I. japonica Thunb. and I. wattii Baker, but can be distinguished by its giant leaves and large purple flowers. Phylogenetic trees based on cpDNA data support the separation of I. × ampliflora from other closely related species in the section Lophiris. According to its morphological features, molecular systematic evidence and chromosome data, we speculate that I. × ampliflora [31 chromosomes] likely is a new hybrid between I. japonica [2n = 32] and I. wattii [2n = 30].

Due to the advantages of easy harvesting and escaping from immune rejection, autologous bone marrow-derived mesenchymal stem cells (BMSCs) are promising in immunosuppressive therapy against inflammation and autoimmune diseases. However, it is still a challenge because the immunomodulatory properties of BMSCs always are impaired by the immunopathogenesis in patients. Because of reliable and extensive multiple biological activities, osthole have got more and more clinical attention. In this article, we found that BMSCs derived from osteoporosis donors was ineffective in cell therapy for experimental inflammatory colitis and osteoporosis.In vivo and in vitro tests showed that due to the downregulated Fas and FasL expression, the ability of osteoporotic BMSCs to induce T cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved its treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pretreatment. In this study, our data unravel a new approach that pharmacological modification (i.e., osthole) can improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance the immunosuppressive therapy of BMSCs might be significantly improved by these findings. Funding Statement: This work was supported by Nature Science Foundation of China (81800979 to Yang Yu.， 31970783 to Deqin Yang, 81700958 to Liang Chen, 32000577 to Bingyi Shao,81800958 to Dou Lei). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All the animal experiments were conducted under the experimental animal guidelines of the National Institutes of Health and approved by the Animal Care and Use Committee of Chongqing Medical University.

Background Neuromyelitis optica spectrum disorders (NMOSD) are associated with recurrent episodes of optic neuritis and transverse myelitis, often resulting in high attack-related disability. Therapeutic apheresis has been recommended as a second-line treatment for steroid-refractory NMOSD. To assess the efficacy and safety of two apheresis techniques, lymphoplasmapheresis (LPE) and therapeutic plasma exchange (TPE), in refractory NMOSD and to provide a new treatment option for patients with refractory NMOSD. Methods This retrospective study examined NMOSD patients who had undergone either LPE or TPE treatment between January 2015 and January 2018. The patients were monitored for improvements in disabilities, incidences of adverse reactions, and safety of the procedure over a one-year follow-up period. The primary outcome measures included changes in the visual outcome scale (VOS) score, the expanded disability status scale (EDSS), and the annualized relapse rate (ARR). Results Neurological function and objective response rates were significantly improved in 76.5% of patients treated with LPE and 83.3% of patients treated with TPE. There were no significant differences in the two treatment groups (P=0.392). Similarly, there were no differences in the reduction in the relative relapse rate between the two groups (P=0.494). Adverse reactions, mostly of mild or moderate intensity, were recorded in 9.3% of procedures in 38% of patients. The most commonly observed adverse events (AEs) were similar between the two treatment cohorts. Conclusions Patients treated with LPE showed improved neurological function comparable to that reported with TPE treatment. No superiority was shown for either of the apheresis techniques.

Rationale and Objectives The purpose of this study was to investigate the role of computed tomography (CT) radiomics for the prediction of the human epidermal growth factor 2 (HER2) status in patients with gastric cancer. Methods One hundred and thirty two consecutive patients with advanced gastric cancer undergoing radical gastrectomy were retrospectively reviewed. All patients received preoperative contrast CT examination, and immunohistochemistry results of their HER2 status were available. All the subjects were randomly divided into a training cohort (n = 90) and a test cohort (n = 42). Arterial phase (AP) and portal phase (PP) contrast CT images were retrieved for tumor segmentation and feature extraction. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate the performance of the radiomics classifiers. Results Among the 132 patients, a total of 99 patients were HER2 negative, and the remaining 33 patients were border line or positive. The AP radiomics model could distinguish HER2-negative cases with an AUC of 0.756 (95% confidence interval [CI]: 0.656–0.840) in the training cohort, which was confirmed in the test cohort with AUC of 0.830 (95% CI: 0.678–0.930). The PP radiomics model showed AUCs of 0.715 (95% CI: 0.612–0.804) and 0.718 (95% CI: 0.554–0.849) in the training and test cohort for distinction of negative HER2 cases, respectively. Conclusion Radiomics models based on standard-of-care CT images hold promise for distinguishing HER2-negative gastric cancer.

Naqi Lian,1,2,* Mengxi Shen,1,2,* Kai Zhang,1,2,* Jiacheng Pan,1,2 Yi Jiang,1,2 Yang Yu,1,2 Yonghao Yu1,2 1Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 2Tianjin Institute of Anesthesiology, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Yu; Yonghao YuDepartment of Anesthesiology, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, People’s Republic of ChinaEmail sevenyu1987@outlook.com; yuyonghao@126.comIntroduction: Chemotherapy-induced neuropathic pain (CINP) is one of the most common complications of chemotherapeutic drugs which limits the dose and duration of potentially life-saving anticancer treatment and compromises the quality of life of patients. Our previous studies have reported that molecular hydrogen (H2) can be used to prevent and treat various diseases. But the underlying mechanism remains unclear. The aim of the present study was to explore the effects of hydrogen-rich water on gut microbiota in CINP.Methods: All C57BL/6J mice were divided into 4 groups: The group fed with normal drinking water and injected with saline (H2O + Saline), the group fed with normal drinking water and injected with oxaliplatin (H2O + OXA), the group fed with hydrogen-rich water and injected with saline (HW + Saline), and the group fed with hydrogen-rich water and injected with oxaliplatin (HW + OXA). The mechanical paw withdrawal threshold of the mice was tested on days 0, 5, 10, 15 and 20 after hydrogen-rich water treatment. On day 20, feces of mice from different groups were collected for microbial community diversity and structure analysis. The levels of inflammatory cytokines (TNF-α and IL-6), oxidative stress factors (OH- and ONOO-), lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) were detected in dorsal root ganglia (DRG), L4-6 spinal cord segments and serum by enzyme-linked immunosorbent assay. The expression of TLR4 in DRG and spinal cords was determined by Western blot.Results: The results illustrated that hydrogen-rich water could alleviate oxaliplatin-induced hyperalgesia, reduce the microbial diversity and alter the structure of gut microbiota, reverse the imbalance of inflammatory cytokines and oxidative stress, and decrease the expression of LPS and TLR4.Conclusion: Hydrogen-rich water may alleviate CINP by affecting the diversity and structure of the gut microbiota, and then the LPS-TLR4 pathway, which provides a direction for further research.Keywords: hydrogen-rich water, gut microbiota, CINP, LPS-TLR4 pathway

Interleukin-22 (IL-22), secreted by tumor infiltrated lymphocytes, is identified as a tumor-promoting factor in certain cancers, which was secreted by tumor infiltrated lymphocytes. However, the role of IL-22 in breast cancer remains conflicting. In this study, we assessed the expression of IL-22, IL-22 receptor 1 (IL-22R1), CD4, CD8, FOXP3, and CD68 in breast cancer by immunohistochemistry. IL-22 expression was exhibited in 105 (69.1%) cases in tumor cells (tIL-22), whereas only 24 (15.8%) samples displayed IL-22 expression in stromal cells. Multivariate analysis showed that tIL-22 expression was a poor prognostic factor for overall survival (OS) (

The model provided by the International Classification of Functioning, Disability and Health (ICF) is used to describe, classify and measure function in both health care practice and research. ICF for Children and Youth (ICF-CY) has not been applied to the rehabilitation of patients with visual impairment. The purpose of this case report is to describe the process of evaluation and treatment of low vision patients based on ICF-CY models. The patient was a 9-year-old girl. The diagnosis included retinopathy of prematurity (ROP) (OU), secondary glaucoma after iridectomy (OD), keratoleukoma (OD), retinal detachment (OS), strabismus postoperation (OU), nystagmus. The patient complained of being unable to see clearly, of fear of falling down stairs and of being unable to study normally. The ICF-CY framework is used to assess the overall function and disability of this girl. We provided visual devices and instruction to improve the body structure and function, mobility restriction and environmental factors associated with the cognitive function of patients. The results showed that with the help of devices and the guidance of her parents, friends and health professionals, the patient's cognitive function, learning ability and social ability were significantly improved and her psychological conditions had also been improved. As a result, using the ICF-CY model to evaluate and intervene in patients is helpful for accurately dealing with different functional problems and their correlations.

Current clinical treatment targeting osteosarcoma (OS) are limited for OS patients with pulmonary metastasis or relapse, which led to high mortality (70%-85%) for advanced osteosarcoma patients. Although ongoing efforts have been made to illustrate the mechanisms of tumorigenesis and progression in OS; however, it was far for us to learn a comprehensive molecular mechanism implies in OS development. In our study, we implicated a circRNA hsa_circ_0002137, which was higher expressed in osteosarcoma tumours compared with paracancerous tissue. The dysregulated expression pattern was also found in osteosarcoma cell lines. The role of circ_0002137 was explored via down- or up-regulated experiments. It was proved that down-regulation of circ_0002137 suppressed the progress of OS, including cell invasion, cell cycle and cell apoptosis. Furthermore, the correlation between circ_0002137 and miR-433-3p was predicted using bioinformatic tools and verified utilizing RNA pull-down assay and luciferase reporter assay. Interestingly, we found that the inhibitory effect of circ_0002137 on OS was dependent of insulin-like growth factor-1 receptor (IGF1R). In conclusion, it was demonstrated that circ_0002137 could restrain the progression of OS through regulating miR-433-3p/IGF1R axis, providing a comprehensive landscape of circ_0002137 in the generation and development of OS.

Sevoflurane could stimulate neurotoxicity and result in postoperative cognitive dysfunction (POCD). Long non-coding RNAs (lncRNAs) have been implicated in the regulation of nervous system disease. This study was performed to investigate role and mechanism of lncRNA Rian (RNA imprinted and accumulated in nucleus) in sevoflurane anesthesia-induced cognitive dysfunction. Mice post-sevoflurane anesthesia showed cognitive impairments and neuronal damage and apoptosis. However, intracerebroventricularly injection with Adenovirus (Ad) for the over-expression of Rian ameliorated sevoflurane-induced neuronal damage and apoptosis. Cognitive impairments induced by sevoflurane were attenuated by injection with Ad-Rian. Moreover, transfection with Ad-Rian also protected isolated primary hippocampal neurons against sevoflurane-induced decrease of cell viability and increase of lactic acid dehydrogenase (LDH) and apoptosis. Mechanistically, Rian bind to miR-143-3p, and decreased expression of LIMK1 (Lim kinase 1) through negative regulation of miR-143-3p. Knockdown of LIMK1 aggravated sevoflurane-induced decrease of cell viability and increase of LDH and apoptosis in neurons, while over-expression attenuated LIMK1 silence-induced neuronal damage post-sevoflurane anesthesia. In conclusion, Rian demonstrated neuroprotective effects against sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis, providing promising target for sevoflurane anesthesia-induced cognitive dysfunction.

Purpose: To comparing the survival in different strategies, preoperative systemic treatment (PST) versus upfront surgery (US) in patients of HER2-positive early breast cancer in real-world.Methods: Eligible patients from 2012 to 2015 were classified as PST or US group prospectively, according to the real upfront treatment. The primary endpoint is disease-free survival (DFS), the second endpoint is overall survival (OS). All the outcomes were examined in unadjusted model, propensity score matching (PSM) model, and inverse probability of treatment weighting (IPTW) model. Results: Finally, 1067 eligible patients (215 in PST group, 852 in US group) were included into analysis (Table 1). In unweighted analysis, the cumulative DFS of PST group was significantly lower than US group (78.1% vs 87.7%, P *Proportions and medians are weighted using IPTW, all covariates included in the propensity analysis. Abbreviations: PSM, propensity score matching, IPTW, inverse probability of treatment weighting, PST, preoperative systemic treatment, US, upfront surgery, SMD, standardized mean difference, ER, estrogen receptor, PR, progesterone receptor.In IPTW model, the DFS rate of the PST group was 81.3% versus 80.8% of the US group, and the OS rate of the PST group was 92.1% versus 90.3% (Figure 2E, 2F), both having no significantly differences (Table 4). In further stratified analysis (Figure 3E, 3F), as in PSM model, the DFS and OS rate of the patients without pCR after PST (73.1%, 88.4%) were worse than those with pCR (96.6%, 99.3%) and US group (80.8%, 90.3%), respectively. Table 1. The clinicopathologic characteristics of two groups in PSM and IPTW modelsCharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMDN (%)N (%)N (%)N (%)N (%)N (%)Age (years, medium, 95%CI)50, 39~6150, 33~640.0550, 40~6549, 34~620.1049, 39~6750, 31~640.03Stage T14588 (3.7)450 (52.8)0.7018(3.7)10 (6.9)0.03280 (10.5)450 (44.1)0.4672529157 (73.0)372 (43.7)118 (81.4)116 (80.0)635 (83.0)458 (44.9)38050 (23.3)30 (3.5)19 (13.1)19 (13.1)50 (6.5)113 (11.1)Stage N057137 (17.2)534 (62.7)1.04837 (17.2)32 (22.1)0.081310 (40.5)538 (52.7)0.2461596178 (82.8)318 (37.3)108 (81.4)113 (77.9)455 (59.5)483 (47.3)Grade1 and 252292 (42.8)430 (50.5)0.15477 (53.1)89 (61.4)0.168345 (45.1)493 (48.3)0.0643545123 (57.2)422 (49.5)68 (46.9)56 (38.6)420 (54.9)528 (51.7)ERNegative536142 (66.0)394 (46.2)0.40787 (60.0)68 (46.9)0.265386 (50.5)513 (50.2)0.004Positive53173 (34.0)458 (53.8)58 (40.0)77 (53.1)379 (49.5)508 (49.8)PRNegative649171 (79.5)478 (56.1)0.418108 (74.5)113 (77.9)0.081499 (65.2)625 (61.2)0.083Positive41844 (20.5)374 (43.9)37 (25.5)32 (22.1)266 (34.8)396 (38.8) Citation Format: Yang Hongjian, Xingfei Yu, Chen Wang, Zheng Yabing, Hu Jiejie, Xiying Shao, Liming Sheng, Juan Lin, Yuqin Ding, Haojun Xuan, Lijie Gong, Weiliang Feng, Chengdong Qin, Daobao Chen, Yang Yu. Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-52.

To explore the role of radiomics in integrating primary tumor and peritumoral areas based on PET-CT scans for predicting E-cadherin (E-cad) expression in early-stage cervical cancer (ESCC) and its correlation with pelvic lymph node metastasis (PLNM). Ninety-seven ESCC patients who had undergone PET-CT scans were retrospectively analyzed. The ROI of primary tumors, peritumoral areas, and plus tumors were semi-automatically segmented on PET-CT images. A total of 1188 radiomics features were extracted, selected, and eventually integrated into radiomics score (rad-score). The rad-score difference between patients with E-cad expression of high and low was analyzed using Mann-Whitney tests. Characteristic correlation was tested using a Spearman analysis. Four models were established using logistic regression algorithms and evaluated using ROC and calibration curves. A DeLong test was used to perform pairwise comparisons of AUCs. The rad-score of patients with low E-cad expression was higher than that of patients with high E-cad expression in both training and testing cohorts (p < 0.001 and p = 0.027, respectively). A significant correlation was observed between the rad-score and E-cad (p < 0.001). PLNM correlated slightly with rad-score and E-cad values (p = 0.01 and p < 0.001, respectively). The ROC curve and calibration curve of the rad-score model performed best in both training and testing cohorts (AUC = 0.915, 0.844, p < 0.001, respectively). The radiomics of integrating primary tumor and peritumoral areas based on PET-CT showed correlations with PLNM. It was also able to predict E-cad expression in ESCC patients, allowing for evaluation of those patients’ prognosis and more individualized medical treatment. • By integrating the primary tumor and peritumoral area based on PET-CT, radiomics was feasible. • The rad-score was associated with E-cad expression and PLNM in patients with ESCC. • Radiomics that integrated the primary tumor and peritumoral areas based on PET-CT could predict E-cad expression in patients with ESCC.

Axillary lymph node dissection is an indispensable step in modified radical mastectomy for breast cancer. It is the most reliable method and the golden standard to determine the status of axillary lymph nodes. It is also of great importance to evaluate the prognosis and develop treatment plans for breast cancer patients. Axillary lymph node dissection can be anatomically divided into levels I, II, and III. Level I and Level II axillary lymph dissection is the standard clinical treatment of axillary lymph nodes positive breast cancer, whereas level III axillary lymph node dissection has been controversial. Level III axillary lymph node metastasis is one of the important factors that can easily cause distant metastasis and recurrence. It is also an important index to estimate the prognosis of breast cancer patients. To facilitate the decision of whether or not to perform level III lymph node dissection, we reviewed the indications, complications, and surgical procedures of level III lymph node dissection.

Background Ovarian mucinous cystadenomas with situs inversus totalis (SIT) are infrequent in pubertal girls. Surgical techniques on their treatment without affecting ovary anatomical and physiological function have always been a great challenge. Case A 15-year-old girl presented with abdominal distension and pain due to some huge growths. Computed tomography imaging showed that the heart and whole abdomen viscera were inversely located. Two big low-density masses were found in the abdominopelvic cavity. An exploratory laparotomy was performed and two tumors were removed. Pathology confirmed a mucinous cystadenoma.

The effects of solid carbon on NO electrocatalytic reduction in the presence of O2 content, as low as can be found in a gasoline engine, were investigated. Tubular solid-state fuel cells filled with Fe-loaded carbon materials (Fe-loaded activated carbon, Fe-AC, and Fe-loaded carbon black, Fe-BC) were fabricated for electrochemical reduction in the configuration of LSM as the cathode, NiO-YSZ mixed powder as the anode, and YSZ as the electrolyte. A moderate NO removal efficiency of 60% and maximum peak power density of 0.035 W cm−2 were achieved for Fe-AC in the presence of 1% O2, whereas no such performances were detected in the case of AC. Following TGA-MS and in-situ analyses of exit gases from the anodes, it can be concluded that Fe-loaded carbon materials promote CO formation in Boudouard reactions by utilizing excess oxygen transported from the cathode, which is capable of alleviating the impact of oxygen on NO removal while also enhancing electrical performance. The formation of CO contributes to the reduction of both concentration polarization loss and activation polarization loss at both electrodes.

Peripherally or centrally administered TNF-α elicits a prolonged sympathetically mediated pressor response, but the underlying molecular mechanisms are unknown. Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in cardiovascular regions of the brain has recently been recognized as a key mediator of sympathetic excitation, and ERK1/2 signaling is induced by activation of epidermal growth factor receptor (EGFR) tyrosine kinase activity. The present study examined the role of EGFR and ERK1/2 signaling in the sympathetic response to TNF-α. In urethane-anesthetized rats, intracarotid artery injection of TNF-α increased phosphorylation of EGFR and ERK1/2 in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN); upregulated the gene expression of excitatory mediators in SFO and PVN; and increased blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA). A continuous intracerebroventricular infusion of the selective EGFR tyrosine kinase inhibitor AG1478 or the ERK1/2 inhibitor PD98059 significantly attenuated these responses. Bilateral PVN microinjections of TNF-α also increased phosphorylated ERK1/2 and the gene expression of excitatory mediators in PVN, along with increases in BP, HR, and RSNA, and these responses were substantially reduced by prior bilateral PVN microinjections of AG1478. These results identify activation of EGFR in cardiovascular regulatory regions of the forebrain as an important molecular mediator of TNF-α-driven sympatho-excitatory responses and suggest that EGFR activation of the ERK1/2 signaling pathway plays an essential role. These mechanisms likely contribute to sympathetic excitation in pathophysiological states like heart failure and hypertension, in which circulating and brain TNF-α levels are increased. NEW & NOTEWORTHY Proinflammatory cytokines contribute to the augmented sympathetic nerve activity in hypertension and heart failure, but the central mechanisms involved are largely unknown. The present study reveals that TNF-α transactivates EGFR in the subfornical organ and the hypothalamic paraventricular nucleus to initiate ERK1/2 signaling, upregulate the gene expression of excitatory mediators, and increase sympathetic nerve activity. These findings identify EGFR as a gateway to sympathetic excitation and a potential target for intervention in cardiovascular disease states.

Introduction Ovine interferon-tau (oIFN-τ) is a newly discovered type I interferon. This study used biochemical techniques to transform the oIFN-τ gene into Escherichia coli to obtain the mass and soluble expression of the recombinant protein. Material and Methods First, total RNA was extracted from fresh sheep embryonic tissues with TRIzol reagent and then used as a template to reverse transcribe and amplify the mature oIFN-τ gene with RT-PCR. The amplified product was next digested with the HindIII and XhoI restriction enzymes and inserted into the pET-32a(+) vector to construct the prokaryotic expression plasmid. The corrected in-frame recombinant plasmid, pET-32a(+)-oIFN-τ, was transformed into E. coli Rosetta (DE3) competent cells. After induction with isopropyl-beta-D-thiogalactopyranoside (IPTG), the recombinant protein was detected in bacteria. Finally, the bacteria were lysed by sonication, and the recombinant protein was purified by nickel affinity chromatography and DEAE anion exchange chromatography. Results The protein was confirmed to be oIFN-τ, which mainly existed in the soluble lysate fraction, as proven by SDS-PAGE and Western blot assays. Conclusion Purified IFN-τ exists mostly in a soluble form, and its anti-vesicular stomatitis virus (VSV) activity reached 7.08×10(6)IU/mL.

To evaluate the contributory value of positron emission tomography (PET)-intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the prediction of lymphovascular space invasion (LVSI) in patients with cervical cancer without lymphatic metastasis. A total of 90 patients with cervical cancer without signs of lymph node metastasis on PET/MRI were enrolled in this study. The tumours were classified into LVSI-positive (n = 25) and LVSI-negative (n = 65) groups according to postoperative pathology. The PET-derived parameters (SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) and IVIM-derived parameters (ADCmean, ADCmin, Dmean, Dmin, f, D* and gross tumour volume (GTV)) between the two groups were evaluated using a Student’s t test (Mann-Whitney U test for variables with a nonnormal distribution) and receiver operating characteristic (ROC) curves. The optimal combination of PET/MR parameters for predicting LVSI was investigated using univariate and multivariate logistic regression models and evaluated by ROC curves. The optimal cutoff threshold values corresponded to the maximal values of the Youden index. A control model was established using 1000 bootstrapped samples, for which the performance was validated using calibration curves and ROC curves. PET-derived parameters (SUVmax, SUVmean, MTV, TLG) and IVIM MRI-derived parameters (Dmin, ADCmin, GTV) were significantly different between patients with and without LVSI (P < 0.05). Logistic analyses showed that a combination of TLG and Dmin had the strongest predictive value for LVSI diagnosis (area under the curve (AUC), 0.861; sensitivity, 80.00; specificity, 86.15; P < 0.001). The optimal cutoff threshold values for Dmin and TLG were 0.58 × 10−3 mm2/s and 66.68 g/cm3, respectively. The verification model showed the combination of TLG and Dmin had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.878) and consistency. The combination of TLG and Dmin may be the best indicator for predicting LVSI in cervical cancer without lymphatic metastasis.

Objective To investigate the therapeutic efficacy of titanium elastic intramedullary nail (TEN) and open reduction and internal fixation with plate (ORIF) in the treatment of humeral fracture in children. Methods A retrospective study was carried out in a total of 69 patients who were admitted to the hospital from January 2013 to December 2018. These patients, including 41 males and 28 females, were aged from 6 to 12 years old with a median of 8 years. These patients were diagnosed with humeral fracture and underwent the surgery of ORIF (n = 22) or TEN (n = 47). The intraoperative bleeding, operation time, length of stay (LOS), and fracture healing time were compared between the two groups. The therapeutic effect was assessed by the shoulder range of motion, the elbow range of motion, the UCLA shoulder function score, and the Mayo elbow performance score (MEPS) 6 months after the surgery. Results The intraoperative bleeding (97.20 ± 27.83 mL vs 185.60 ± 37.50 mL, P, Compared with the open reduction and internal fixation with plate, titanium elastic intramedullary nail can be a good technique for the treatment of humeral fracture in children, with the advantages of less intraoperative bleeding, shorter operative time, quicker healing, and better recovery of shoulder mobility and range of motion.

Cell membranes are complicated multicomponent structures, related to many basic cellular processes, such as substance transporting, energy conversion, signal transduction, mechanosensing, cell adhesion and so on. However, cell membranes have long been difficult to study at a single-molecule level due to their complex and dynamic properties. During the last decades, biophysical imaging techniques, such as atomic force microscopy and super-resolution fluorescent microscopy, have been developed to study biological structures with unprecedented resolution, enabling researchers to analyze the composition and distribution of membrane proteins and monitor their specific functions at single cell/molecule level. In this review, we highlight the structure and functions of cell membranes based on up-to-date biophysical techniques. Additionally, we describe the recent advances in force-based detecting technology, which allow insight into dynamic events and quantitativelymonitoring kinetic parameters for trans-membrane transporting in living cells.

Peritoneal mesothelioma (PM) is a rare and aggressive primary peritoneal malignancy characterized by widespread multiple metastatic tumour nodules originating from the peritoneum. The conventional classification distinguishes diffuse malignant peritoneal mesothelioma (DMPM) and border-line forms: multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). Despite the novel achievements in the management of PM, there is difficulty in conducting randomized trials due to its rarity and aggressive biology in many cases. As there is, a necessity to standardize diagnosis and management of PM, the Peritoneal Surface Oncology Group International (PSOGI) commissioned a steering committee to elaborate clinical guidelines.

This was a national survey that determined the prevalence of depressive symptoms (depression thereafter) and its relationship with quality of life (QOL) in frontline clinicians working in psychiatric hospitals in China during the COVID-19 pandemic. Depression and QOL were assessed using the Patient Health Questionnaire nine items (PHQ-9) and the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF), respectively. Multivariable logistic regression analyses and analysis of covariance were used. A total of 10,516 frontline clinicians participated in this study, of which, 28.52% (n=2,999) met screening criteria for depression. Compared to those without depression, clinicians with depression had a lower quality of life (F (1, 10515) =2874.66, P

Inspired by aspirin and chalcone, herein, we describe a modular biomimetic strategy to achieve a new class of CF3-bearing benzannulated macrolactams. The key to the success of macrolactams was the utilization of a highly chemoselective Rh(iii)-catalyzed native carboxylic acid-directed C-H alkylation. Moreover, the unique CF3-containing benzannulated macrocycles showed decent immunosuppressive effects on B cells in vitro, including proliferation, activation, and antibody production upon specific stimulation implicating TLR and BCR signaling.

Genome‐wide 5hmC profiling in cell‐free DNA acquired from CRC patients, adenoma patients, and healthy individuals revealed that the differential 5hmC‐modified regions were gathered into four clusters with no overlap, although there are a few overlapped genes shared between the different clusters. CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, which was consistent with the ‘parallel’ evolution hypothesis in adenoma., Approximately 85% colorectal cancers (CRCs) are thought to evolve through the adenoma‐to‐carcinoma sequence associated with specific molecular alterations, including the 5‐hydroxymethylcytosine (5hmC) signature in circulating cell‐free DNA (cfDNA). To explore colorectal disease progression and evaluate the use of cfDNA as a potential diagnostic factor for CRC screening, here, we performed genome‐wide 5hmC profiling in plasma cfDNA and tissue genomic DNA (gDNA) acquired from 101 samples (63 plasma and 38 tissues), collected from 21 early‐stage CRC patients, 21 AD patients, and 21 healthy controls (HC). The gDNA and cfDNA 5hmC signatures identified in gene bodies and promoter regions in CRC and AD groups were compared with those in HC group. All the differential 5hmC‐modified regions (DhMRs) were gathered into four clusters: Disease‐enriched, AD‐enriched, Disease‐lost, and AD‐lost, with no overlap. AD‐related clusters, AD‐enriched and AD‐lost, displayed the unique 5hmC signals in AD patients. Disease‐enriched and Disease‐lost clusters indicated the general 5hmC changes when colorectal lesions occurred. Cancer patients with a confirmable adenoma history segmentally gathered in AD‐enriched clusters. KEGG functional enrichment and GO analyses determined distinct differential 5hmC‐modified profiles in cfDNA of HC individuals, AD, and CRC patients. All patients had comprehensive 5hmC signatures where Disease‐enriched and Disease‐lost DhMR clusters demonstrated similar epigenetic modifications, while AD‐enriched and AD‐lost DhMR clusters indicated complicated subpopulations in adenoma. Analysis of CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, consistent with the ‘parallel’ evolution hypothesis in adenoma, either developed through the adenoma‐to‐carcinoma sequence or not. These findings deepen our understanding of colorectal disease and suggest that the 5hmC modifications of different pathological subtypes (cancer patients with or without adenoma history) could be used to screen early‐stage CRC and assess adenoma malignancy with large‐scale follow‐up studies in the future.

Therapeutic angiogenesis is one promising strategy for the treatment of ischemic heart disease, which is the leading cause of death globally. In recent years, extracellular vesicles (EVs) have quickly gained much attention as a cell-free approach to stimulate angiogenesis. However, clinical applications of EVs are limited by their insufficient targeting capability. Herein, we introduce a method to enhance therapeutic angiogenesis based on platelet membrane-engineered EVs. Methods Platelet-mimetic EVs (P-EVs) were fabricated by fusing the membranes of EVs with platelet membranes by extrusion. A mouse model of myocardial ischemia reperfusion (MI/R) was established and injected with PBS, EVs, and P-EVs to evaluate their targeting ability and therapeutic angiogenesis efficacy. Results P-EVs inherited the adhesive proteins and natural targeting ability to injured vasculature of platelets and retained the pro-angiogenic potential of EVs. In the MI/R model, P-EVs preferentially accumulated in the injured endothelium of the ischemic hearts and enhanced the angiogenesis potency of EVs. Conclusions This engineering strategy to modify pre-isolated EVs with platelet membranes by membrane fusion bestows EVs with the targeting ability of platelets and offers an exciting opportunity to design other targeted EVs fused with cell membranes from different sources for therapeutic angiogenesis.

Phytochemical investigations on the dry leaves of Illicium dunnianum have led to the isolation of 24 lignans. Illiciumlignans G–K (1–5) were five undescribed benzofuran lignans, illiciumlignan L (6) was one undescribed ditetrahydrofuran lignan, illiciumlignans M–O (7–9) were three new sesquilignans, and compounds 10, 12, 13, 15, and 18–21 were firstly isolated from the genus Illicium. Their structures were elucidated by detailed spectroscopic analyses (UV, IR, HR-ESI-MS, and NMR) and CD experiments. All isolates were evaluated by measuring their inhibitory effects on PGE2, and NO production in LPS-stimulated RAW 264.7 macrophages.

Pharmacological stimulation of adipose tissue remodeling and thermogenesis to increase energy expenditure is expected to be a viable therapeutic strategy for obesity. Berberine has been reported to have pharmacological activity in adipose tissue to anti-obesity, while the mechanism remains unclear. Here, we observed that berberine significantly reduced the body weight and insulin resistance of high-fat diet mice by promoting the distribution of brown adipose tissue and thermogenesis. We have further demonstrated that berberine activated energy metabolic sensing pathway AMPK/SIRT1 axis to increase the level of PPARγ deacetylation, which leads to promoting adipose tissue remodeling and increasing the expression of the thermogenic protein UCP-1. These findings suggest that berberine that enhances the AMPK/SIRT1 pathway can act as a selective PPARγ activator to promote adipose tissue remodeling and thermogenesis. This study proposes a new mechanism for the regulation of berberine in adipose tissue and offers a great prospect for berberine in obesity treatment.

On January 21, 2020, the Centers for Medicare & Medicaid Services issued the Decision Memo for Acupuncture for Chronic Low Back Pain, which included acupuncture treatment for chronic low back pain in Medicare. This paper analyzed the characteristics and analytic methods of CMS evidence review. The evidence review of CMS is characterized by focusing on reviewing domestic and international review studies, U.S. evidence-based guidelines, public consultation and patient needs and personnel coverage. The evidence review and analytic method of CMS includes reviewing the literature to evaluate relevant evidence, reviewing the quality and basis of evidence and determining the universality of evidence. The evidence review method of CMS provides enlightenment for the development of acupuncture and moxibustion and the promotion of Traditional Chinese Medicine. China can learn from the experience of CMS and carry out evidence-based medical evaluation of acupuncture and moxibustion around the common diseases in China. We can improve the coverage of medical insurance according to the needs of patients and encourage physicians to give patient education on non-drug therapy.

Context Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. Objective This study explores the RA protective effect on APAP-induced ALI and its mechanism. Materials and methods Sixty Kunming mice 6–8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. Results Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p

Objective Riedel's thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4-related disease (IgG4-RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied. Design A case series and literature review. Patients and measurements We searched our hospital's pathology database and identified five cases of RT between 2000 and 2019. The expression levels of IgG4 and IgG in thyroid tissues were detected by immunohistochemistry. We also performed a literature search of the electronic databases PubMed/MEDLINE, Web of Science and China National Knowledge Internet (CNKI). Eight papers were included in this study. Results According to immunohistochemistry, the numbers of IgG4+ plasma cells per high-power field (HPF) of the five RT patients at our hospital were 80, 8, 50, 10 and 22, and the respective IgG4+/IgG+ ratios were 76%, 80%, 43%, 19% and 28%. In the literature, 15 RT patients with confirmed IgG4 and IgG immunohistochemical findings were identified. Only seven of them fulfilled the IgG4-RD diagnostic criteria in terms of immunohistochemistry (IgG4+ > 10/HPF, IgG4+/IgG+ > 40%). In order to ensure that most RT cases can meet the IgG4 immunohistochemical criteria, an organ-specific cut-off value (≥10 IgG4+ plasma cells/HPF and ≥ an IgG4+/IgG ratio of 20%) was finally selected in our study. Conclusion Our findings of IgG4 expression in patients with RT suggest that a cut-off of 10 IgG4+ plasma cells/HPF and an IgG4+/IgG ratio of 20% are more suitable diagnostic criteria for RT in IgG4-RD.

Background Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine. Methods We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis. Results Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4–21.3%] and 3.9% (95% CI 0.9–8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8–26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1–17.2%). Measures of heterogeneity between studies were high for all outcomes (I2 = 89–100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results. Conclusions This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.

Mounting evidence shows that long noncoding RNAs play important roles in human diseases and radioresistance could be an important factor for tumor recurrence. We observed that HOX antisense interge...

Because chondrocytes are the only resident cells in articular cartilage, the steady state of these cells is important for the maintenance of joint function. In various osteoarthritis diseases, chondrocytes undergo a series of pathophysiologic changes, leading to the loss of chondrocytes and the degradation of extracellular matrix (ECM). This study found that Cytoplasmic localized histone deacetylase 6 (HDAC6) is up-regulated on the articular surface in a destabilization of the medial meniscus-induced mouse osteoarthritis model. Because HDAC6 is highly related to the acetylation of tubulin and the function of the microtubule system is closely related to material transport and signal transduction, the relationship between the expression level or activity of HDAC6 and the fate of chondrocytes in vitro and in vivo were confirmed. Primary chondrocytes overexpressing DNA-HDAC6 with plasmid were constructed in vitro, and HDAC6 inhibitor Tubastatin A was selected to inhibit HDAC6 enzyme activity in vivo and in vitro. Subsequently, mitochondrial spatial arrangement, degradation of ECM, and pathological changes in joint were defined. The results indicate that overexpression of HDAC6 causes mitochondrial dysfunction and promotes reactive oxygen species production, leading to degradation of ECM. Tubastatin A treatment after osteoarthritis ameliorates the degradation of cartilage and improves the microenvironment and function of the joint. HDAC6 may be targeted to treat osteoarthritis.

Post-traumatic stress disorder (PTSD), an anxiety-related syndrome, is associated with increased risk for cardiovascular diseases. The present study investigated whether predator scent (PS) stress, a model of PTSD, induces sensitization of hypertension and anxiety-like behaviors and underlying mechanisms related to renin-angiotensin systems (RAS) and inflammation. Coyote urine, as a PS stressor, was used to model PTSD. After PS exposures, separate cohorts of rats were studied for hypertensive response sensitization (HTRS), anxiety-like behaviors, and changes in plasma levels and mRNA expression of several components of the RAS and proinflammatory cytokines (PICs) in the lamina terminalis (LT), paraventricular nucleus (PVN), and amygdala (AMY). Rats exposed to PS as compared to control animals exhibited (1) a significantly greater hypertensive response (i.e., HTRS) when challenged with a slow-pressor dose of angiotensin (ANG) II, (2) significant decrease in locomotor activity and increase in time spent in the closed arms of a plus maze as well as general immobility (i.e., behavioral signs of increased anxiety), (3) upregulated plasma levels of ANG II and interleukin-6, and (4) increased expression of message for components of the RAS and PICs in key brain nuclei. All the PS-induced adverse effects were blocked by pretreatment with either an angiotensin-converting enzyme antagonist or a tumor necrosis factor-α inhibitor. The results suggest that PS, used as an experimental model of PTSD, sensitizes ANG II-induced hypertension and produces behavioral signs of anxiety, probably through upregulation of RAS components and inflammatory markers in plasma and brain areas associated with anxiety and blood pressure control.

Antibiotic (ATB) use seems to negatively affect the outcomes of immune checkpoint inhibitors (ICIs). The aim of this review is to clarify whether ATB use influences the efficacy of ICI treatment in cancer patients. Databases of MEDLINE, Embase, and Cochrane Library were searched for reports published in English between January 2007 and December 2019. We included studies that compared the outcomes of ATB use and no-ATB use in cancer patients using ICIs. Two reviewers independently selected eligible studies and extracted the data. Meta-analysis was performed with pooling of unadjusted hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and with pooling of odds ratios (ORs) for objective response rate (ORR). Thirty-eight studies involving 8409 patients were finally included for qualitative or quantitative analyses. Cancer types included renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, melanoma, gastrointestinal cancer, and others. Meta-analyses revealed that ATB use was associated with poor OS [HR: 1.80, 95% confidence interval (CI): 1.44-2.26, P

Pancreatic cancer has been becoming the second cause of cancer death in the western world, and its disease burden has increased. Neoadjuvant therapy is one of the current research hotspots in the field of pancreatic cancer, aiming to improve the surgical rate and prognosis of pancreatic cancer. Based on the latest evidence, this review discussed neoadjuvant therapy in pancreatic cancer from the following three aspects: patient selection, protocols selection of neoadjuvant therapy, and treatment response evaluation and resectability prediction. A big controversy existed on the indications of neoadjuvant treatment, but it was agreed that any patient who is likely to achieve R0 resection due to neoadjuvant therapy should be the targeted population. A variety of chemotherapy regimens were tried for neoadjuvant therapy in pancreatic cancer, and FOLFIRINOX and Nab-Paclitaxel plus Gemcitabine are two preferred regimens at present. It was challenging to evaluate treatment response and predict resectability after neoadjuvant therapy, although imaging by CT is widely used. Based on new findings of the remarkable performance of several chemotherapy regimens with or without radiotherapy, the neoadjuvant indications of pancreatic cancer have extended in recent years. However, it is still a challenge to assess the neoadjuvant treatment response and determine the timing of surgery.

A retrospective study.The aim of this study was to make a thorough comparison of clinical and radiographic outcomes between ankylosing spondylitis (AS) patients with severe kyphosis who underwent one- or two-level pedicle subtraction osteotomy (PSO) and to determine the indications of one-level PSO.Traditionally, one-level PSO was considered being able to obtain 35° to 40° correction. However, in our practice, one-level PSO might achieve satisfied clinical and radiographic outcomes in AS patients with severe thoracolumbar kyphosis defined as global kyphosis (GK) ≥80°.Fifty-five AS-related severe thoracolumbar kyphosis patients undergoing one- or two-level PSO from January 2007 to November 2016 were reviewed. The radiographic parameters included thoracic kyphosis (TK), lumbar lordosis (LL), GK, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), sagittal vertical axis (SVA), and femoral obliquity angle (FOA). Clinical outcomes were evaluated by Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS).The mean follow-up period was 39.7 ± 20.2 months (range, 24-120 months). Patients who underwent one-level PSO have significantly smaller preoperative GK, SVA, FOA, and larger preoperative LL and SS compared to those who underwent two-level PSO (P 0.05). The optimal cutoff points of preoperative radiographic parameters for selecting one-level PSO were: GK94°, SVA18.0 cm, and LL18°. No significant difference was observed between the two groups with regard to preoperative ODI and VAS (P 0.05), and the improvement of ODI and VAS (P 0.05). Significantly more operative time, blood loss, and fusion levels were found in two-level PSO group (P 0.05).One-level PSO might be appropriate for selected severe AS-related kyphosis patients with GK94°, SVA18.0 cm, and LL18°. This finding might be beneficial for surgical decision-making in performing one-level PSO, a relatively less risky procedure, to reconstruct the ideal sagittal alignment in AS patients with severe thoracolumbar kyphosis.Level of Evidence: 2.

Objectives To evaluate the safety of low-dose tanezumab in the treatment of knee or hip osteoarthritis (OA). Methods Databases were searched up to September 2019 for phase III randomized controlled trials (RCTs). Eleven phase III RCTs comprising 11,455 patients were eligible. The pooled estimates of safety outcomes were assessed and expressed using relative risks (RRs) and 95% confidence intervals with a random-effects model. Results Tanezumab significantly increased the incidence of rapidly progressive OA (RPOA; RR = 9.07, 95% CI = 1.21–67.90, P = 0.03) and abnormal peripheral sensation (APS; RR = 2.68, 95% CI = 1.64–4.37, P Conclusions These results demonstrate that RPOA and APS should be the most concerning AEs when using tanezumab in OA patients. Additional data are needed to define the optimal dose to minimize risk and to determine the optimal subjects to receive this treatment.

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT‐29, LoVo, LS174T, and DLD‐1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN‐38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line‐derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD‐1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN‐PE38 group was significantly reduced compared with that using control treatment alone. However, the HT‐29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN‐PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans., rBC2LCN lectin showed affinity for colorectal cancer (CRC) cell surface. rBC2LCN‐PE38 suppressed subcutaneous CRC tumor growth rates in mouse models. Lectin drug conjugate therapy could be a novel therapeutic option for CRC.

Background Poa L. is a large genus of grass in Gramineae, among which P. pratensis is widely cultivated as turf and forage. Satellite DNA is the main components of the plant genome. Information of satellites will helpful for dissection the genome composition and definition of the phylogeny relationship of these species. However, the knowledge about the satellites in genus Poa is still limited. Results Four satellite DNAs were identified using the Repeat Explorer pipeline in HiSeq Illumina reads from diploid plants in P. malaca (2n = 26). Two satellites showed high similarity with the previously identified PpTr-1 and PpTr-3, whereas two others are newly identified with the monomer of 326 bp (Poa-326) and 353 bp (Poa-353) respectively. The clone DNAs of PpTr-1 and PpTr-3, and oligonucleotides designed representing satellites Poa-326 and Poa-353 were probed to test on chromosomes across 13 Poa speceis with different polyploidy level by fluorescent in situ hybridization (FISH). PpTr-1, PpTr-3, and Poa-362 were stably positioned in the subtelomeric regions in nearly all species with the variation of hybridization sites number. However, Poa-353 showed different FISH patterns of multiple regions with the variation of hybridization intensity and distribution sites across species. In addition, 5S rDNA and 45S rDNA were used to characterize the genome of the Poa species. Four rDNA FISH patterns were revealed in the tested species. Conclusion Four identified satellite were high conservable across Poa species. Genome distribution of these satellites can be characterized by FISH. The variation of satellite DNAs and rDNA chromosomal distributions between species provide useful information for phylogenetic analysis in genus Poa.

Chromosomal microdeletions and microduplications likely represent the main genetic etiologies for children with developmental delay or intellectual disability. Through prenatal chromosomal microarray analysis, some microdeletions or microduplications can be detected before birth to avoid unnecessary abortions or birth defects. Although some microdeletions or microduplications of chromosome 5 have been reported, numerous microduplications remain undescribed. We describe herein a case of a 30-year-old woman carrying a fetus with a chromosome 5q21.1–q21.3 microduplication. Because noninvasive prenatal testing indicated a fetal chromosome 5 abnormality, the patient underwent amniocentesis at 22 weeks 4 days of gestation. Karyotyping and chromosomal microarray analysis were performed on amniotic fluid cells. Fetal behavioral and structural abnormalities were assessed by color and pulsed Doppler ultrasound. Clinical characteristics of the newborn were assessed during the follow-up. The left lateral ventricle appeared widened on ultrasound, but the infant appeared normal at birth. The 5q21.1–q21.3 microduplication in the fetus was inherited from his mother. There are seven genes in this duplication region, but their main functions are unclear. According to this case report, microduplication in this region could represent a benign mutation. Clinicians should pay attention to the breakpoints and the genes involved when counseling patients with microdeletions and microduplications.

Background The aim of this study was to determine the secondary sex ratio (SSR) of offspring in assisted reproduction technology (ART) in Jilin Province, China, and to analyse the influencing factors associated with SSR. Methods A cross-sectional study of 3833 babies including singletons and twins born to 2990 couples treated by ART between May 2011 and December 2018 was performed. Results The main outcomes of this study were that the SSR of ART babies in Jilin Province was 50.64% and the SSR was associated with fertilization methods (p ). Comparing to in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) (OR = 0.808, 95%CI: 0.681–0.958) decreased the percentage of male babies. Conclusions This study suggests that the SSR of ART births in Jilin Province was lower than the normal level and ICSI had a significant effect on SSR. Though we need more samples to study in the future, we still need to think about the impact of ICSI on SSR in ART.