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To describe clinical and genetic characteristics in a series of Chinese patients with non-syndromic retinitis pigmentosa, a total of 20 unrelated Chinese pedigrees with non-syndromic retinitis pigmentosa were evaluated. Complete ophthalmic examinations data including the Humphrey visual field, spectral domain-optical coherence tomography, full-field electroretinography, and fundus fluorescence were collected and analyzed. Targeted exome sequencing was utilized to investigate variations in 260 known genes of inherited retinal disease, including the 90 known causative retinitis pigmentosa genes. We initially identified the potential candidate variants in the pedigrees, then validated the variants using the Sanger sequencing and performed segregation analysis to verify that the variants constituted disease-causing mutations in these pedigrees. We detected three novel (likely) pathogenic and eight previously reported (likely) pathogenic variations in nine genes reported to be related to non-syndromic retinitis pigmentosa in nine of the pedigrees. We report clinical characteristics of Chinese patients with retinitis pigmentosa and novel mutations responsible for non-syndromic retinitis pigmentosa in Chinese pedigrees, expanding the number of gene mutations associated with this disorder and clarifying its genetic basis in the Chinese population. These data will help with rapid and efficient molecular diagnosis and the study of targeted treatment for retinitis pigmentosa in this population.

Centromere protein M (CENPM) is essential for chromosome separation during mitosis. However, its roles in lung adenocarcinoma (LUAD) progression and metastasis remain unknown. In this study, we aimed to explore the effects of CENPM on LUAD progression as well as the underlying mechanisms. We analyzed the expression of CENPM and its correlation with clinicopathological characteristics using GEO LUAD chip datasets and TCGA dataset. We further investigated the impact of CENPM on LUAD and . In silico analysis and qRT-PCR revealed that CENPM is upregulated in LUAD compared with that in normal lung tissues. Via gain/loss-of-function assays, we further found that CENPM promotes the LUAD cell cycle, cell proliferation, migration and invasion, and inhibits cell apoptosis. The study showed that loss of CENPM inhibits the growth of A549 xenografts. Furthermore, we found that CENPM can promote the phosphorylation of mTOR rather than directly affect the mTOR content. Inhibition of mTOR activity abrogates the promoting effects of CENPM on cell cycle progression, cell proliferation, migration and invasion. Taken together, these results show that CENPM plays an important role in the growth and metastasis of LUAD and may be a promising therapeutic target in LUAD.

To investigate the clinical efficacy and survival factors of microtransplantation (MST) in adult patients with acute myeloid leukemia (AML).For a retrospective analysis of 27 adult patients with AML receiving MST from July 2014 to October 2021, the median age was 59(29-77) years old, 13 cases were ≥60 years old, 14 case were60 years old, 13 cases were male and 14 cases were female. Classification by FAB: AML-M2 6 cases, AML-M4 6 cases, AML-M5 2 cases, AML-M6 2 cases, AML（Undivided type） 9 cases, AML myeloid sarcoma 2 cases (primary AML 21 cases, AML secondary to MDS 6 cases). Cytogenetic analysis showed 25 patients with a normal karyotype, 2 patients with an abnormal karyotype, and 20 patients with an abnormal molecular biology. Induction chemotherapy regimens mainly include: IA, DA, MA or HA regimen, including CAG or CIG in combination with decitabine, and single-agent decitabine. 17 patients achieved complete remission (CR) after 1 course of induction chemotherapy and 4 patients achieved CR after 2 courses of induction chemotherapy. 3 patients received CR by four courses of decitabine, 2 patients received no remission, and 1 patient underwent no induction chemotherapy and were treated direct MST. There were 16 patients with pretransplant CR and 11 patients were not in remission before transplantation. Follow-up mainly used consult patient's medical records and telephone inquiry to observe the adverse effects and efficacy of MST treatment. Survival analysis was performed by Kaplan-Meier method, with the main observation indicators overall survival(OS) and leukemia-free survival(LFS), and performed with the Log-rank test. Multivariate analysis was performed by the Cox regression model.A total of 79 MST were performed in 27 AML patients with good overall safety and no special serious adverse effects. The median time of leukocyte recovery was 13(4-28) days, and the median time of platelet recovery was 13(4-30) days. There were 50 cases of infection, 5 cases of abnormal liver function and 3 cases of abnormal cardiac function. Except for abnormal cardiac function, all other complications did not affect the treatment and were cure. Acute or chronic GVHD, renal insufficiency, abnormal coagulation function, and severe bleeding were not observed during treatment or during follow-up. As of the follow-up date, the median follow-up time of the 27 patients was 79(14-171) months, the median OS time was 62(1-171) months, and the median LFS time was 15(0-171) months. The 2-year OS rate was 65.7%（17/27）, and the 2-year LFS rate was 47.4%（12/27） . The complete response rate of 27 patients treated with MST was 48.1% (13/27). 8 patients relapsed during MST treatment, including 7 patients after the completion of the first MST course and 1 patient after the completion of the second MST course. 2 patients relapsed after the end of the course of MST. 13 patients died, including 10 patients because of disease progression, two patients from severe infection, and one patient from cardiac damage.MST has the advantages of small toxic side effects, complete compatibility of HLA matching is not required, effective avoidance of GVHD and rapid hematopoietic recovery, which can improve OS and LFS in elderly AML and young AML patients, and is one of the treatment options for patients without HLA matching.成人急性髓系白血病患者微移植治疗后的临床疗效及生存分析.探究微移植（MST）治疗成人急性髓系白血病(AML)患者的疗效及生存影响因素.回顾性分析单中心2014年7月至2021年10月接受MST治疗的AML患者27例，中位年龄59（29-77）岁，年龄≥60岁者13例，＜60岁者14例，男13例，女14例。疾病按FAB分型：AML-M2 6例，AML-M4 6例，AML-M5 2例，AML-M6 2例，AML（未分型）9例，AML髓系肉瘤2例（原发AML 21例，MDS继发AML 6例）。细胞遗传学分析示正常核型患者25例，异常核型患者2例，分子生物学异常患者20例。诱导化疗方案主要包括：IA、DA、MA或HA方案，个别使用CAG或CIG联合地西他滨，以及单药地西他滨等方案。诱导化疗1个疗程获完全缓解（CR）的患者17例，2个疗程获得CR的患者4例。地西他滨4个疗程获得CR患者3例，未获缓解的2例，1例患者未行诱导化疗，直接行MST治疗。移植前达CR的患者16例，移植前未缓解的患者11例。随访主要采用查阅患者病历资料以及电话问询，观察MST治疗的不良反应与疗效。通过Kaplan-Meier进行生存分析，主要观察指标总生存期（OS）和无白血病生存（LFS），并进行Log-rank检验。通过Cox回归模型进行多因素分析.27例AML患者共进行79例次MST，总体安全性良好，无特殊严重不良反应发生。患者白细胞恢复中位时间13(4-28)天，血小板恢复中位时间13(4-30)天。发生感染50例次，肝功能异常5例次，心功能异常3例次，除了心功能异常外，其它并发症未影响治疗均治愈。所有患者在治疗期间及随访期间均未观察到急性或慢性移植物抗宿主病（GVHD）、肾功能不全、凝血功能异常及严重出血。截至随访日期，中位随访时间79（14-171）个月，中位OS时间为62（1-171）个月，中位LFS时间为15(0-171)个月。2年OS率为65.7%（17/27），2年LFS率为47.4%（12/27）。27例患者MST治疗后完全缓解率为48.1%（13/27）。8例患者在接受MST治疗过程中复发，其中7例第1次MST疗程完成后复发，1例第2次MST疗程完成后复发。2例患者在MST疗程结束后复发。13例患者死亡，其中10例患者死于疾病进展，2例患者死于严重感染，1例患者死于心脏损害.MST具有药物毒副作用小、不需要HLA配型完全相合、有效避免GVHD、造血恢复快等优势，可改善老年AML和部分年轻AML患者的OS及LFS，是无HLA相合配型患者的治疗选择之一.

Background:. Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS). Methods:. A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score. Results:. A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P

The aim of this proof-of-concept study is to develop a predictive model based on deep learning algorithms to predict working alliances after the first therapeutic session and to provide a basis for clinical decisions.Using a sample of 325 patients and 32 psychotherapists from three university counseling centers, a deep learning algorithm known as fully connected neural networks (FCNNs) was adopted to construct data-driven predictive models. The performance differences between the model including only patient indicators and the model including both patient and therapist indicators were compared. The optimal model was further tested in a general hospital sample of 85 patients and 8 therapists.The model incorporating both patient indicators and therapist-level indicators (R²: 0.30 ± 0.02) performed better than the model incorporating only patient indicators (R²: 0.11 ± 0.02). The performance of this model decreased when being transferred to the independent general hospital sample, but still retained some predictive value (R² = 0.11).This study showed that the inclusion of therapist-level indicators can improve the performance of a predictive model in predicting working alliances. This model could assist clinical decisions on choosing psychotherapists for patients and may also initiate new possibilities for future research.

Background:. Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy. Methods:. A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB–IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8– interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). Results:. We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05). Conclusion:. Circulating Th17 cells in the LACC patients (FIGO stage IIB–IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Background Hip fracture is common and carries high morbidity and mortality; thus, it has become a vital concern. We aim to analyse the present status, worldwide trends in hip fracture and state of clinical research. Methods Publications from 2000 to 2019 were retrieved from the Web of Science database and analysed using a bibliometric methodology. VOSviewer software was utilised for analysis. Results In total, 6139 publications were included, and publications increased annually from 152 in 2000 to 592 in 2019. U.S. researchers have produced the most publications, the highest H-index and the greatest number of citations. Osteoporosis International has published the most papers on the topic. Leading researchers, contributing institutions, their cooperative relationships and scientific masterpieces have been identified. The publications can be divided into five clusters: ‘mortality’, ‘surgical management’, ‘rehabilitation’, ‘osteoporosis’ and ‘epidemiology’. A clear developing trend was described, which began with fracture epidemiology and prevention, transitioned to perioperative management, orthogeriatric care and patient safety and then to functional recovery, disease burden and national audits in recent times. Conclusions Hip fractures result in conditions that extend far beyond orthopaedics concerning epidemiology and preventive medicine, internal medicine and endocrinology, as well as critical care and gerontology. Interest, research and publications are on the rise.

Objectives To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. Methods A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study. Results Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P=2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P =0.58), with evidence of heterogeneity (P=0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P=4.08E-08) and DOT1L (rs4807205; OR= 1.12, P=8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. Conclusions We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.

Background Thyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet. Methods TC cell lines (IHH4 and TPC-1) were used. Flow cytometry was used to identify the surface marker of M2-like tumor-associated macrophages (TAMs) from cell culture. Quantitative real-time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β-catenin pathway, and proliferation/epithelial-mesenchymal transition (EMT)-related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β-catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice. Results Coculture with M2-like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation-related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β-catenin signaling pathway, and suppressed EMT and proliferation-related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model. Conclusion M2-like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β-catenin activation.

Background Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated. Methods To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in GPCM, we assign a risk score to genes in the GPCM and identify risk pathways enriched with the risk genes. Results Analysis of >8300 expression profiles covering ten cancer tissues and blood samples indicates that CTpathway outperforms the current state-of-the-art methods in identifying risk pathways with higher accuracy, reproducibility, and speed. CTpathway recapitulates known risk pathways and exclusively identifies several previously unreported critical pathways for individual cancer types. CTpathway also outperforms other methods in identifying risk pathways across all cancer stages, including early-stage cancer with a small number of differentially expressed genes. Moreover, the robust design of CTpathway enables researchers to analyze both bulk and single-cell RNA-seq profiles to predict both cancer tissue and cell type-specific risk pathways with higher accuracy. Conclusions Collectively, CTpathway is a fast, accurate, and stable pathway enrichment analysis method for cancer research that can be used to identify cancer risk pathways. The CTpathway interactive web server can be accessed here http://www.jianglab.cn/CTpathway/. The stand-alone program can be accessed here https://github.com/Bioccjw/CTpathway.

Noncoding RNAs (ncRNAs), such as lncRNAs, circRNAs and pri-miRNAs, play important roles in physiological and pathological processes. Recently, it was demonstrated that they could encode proteins or peptides. However, relevant information is scattered across numerous published articles, which is inconvenient for the exploration of ncRNA translation by researchers. In this study, we presented an ncEP database, which records the low-throughput experimentally validated (LTEV) proteins or peptides encoded by ncRNAs, from published articles. Collectively, ncEP contains 80 entries including 74 proteins or peptides, 22 lncRNAs, 11 circRNAs, 9 pri-miRNAs and 37 other ncRNAs across 18 species from more than 50 articles of over 2000 candidate articles. We have provided a user-friendly interface for users to search, browse, visualize, download and submit data. In summary, ncEP provides a relatively comprehensive repository of the LTEV proteins or peptides encoded by ncRNAs and will enrich the knowledge for translation process. ncEP is freely available at http://www.jianglab.cn/ncEP/.

Background The surgical treatment of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. In the current study, the authors have reported their surgical outcomes and experience with en bloc retroperitoneal laparoscopic radical nephrectomy (LRN) with inferior vena cava (IVC) thrombectomy for patients with RCC with level 0 to II VTT. Methods A retrospective review of the clinical records of 78 patients who underwent retroperitoneal LRN with IVC thrombectomy from March 2015 to September 2018 was performed. The surgical procedures included establishing the retroperitoneal space, ligating and severing the renal artery, clamping the renal vein and IVC, incising the IVC, and placing the renal and tumor thrombus en bloc into a retrieval bag. Results According to the Mayo classification, the tumor thrombus was level 0, I, and II, respectively, in 28 patients, 27 patients, and 23 patients. The median operative time, estimated blood loss, and postoperative hospital stay were 256 minutes, 400 mL, and 8 days, respectively. A total of 67 patients were not converted to open surgery. No patient died during surgery, and no tumor embolization occurred. Thirteen patients experienced complications. The pathological reports indicated clear cell RCC in 70 patients and other RCC in 8 patients. The median follow-up was 14.5 months, and 61 patients were alive at the time of last follow-up. Conclusions En bloc retroperitoneal LRN with IVC thrombectomy is a challenging but feasible procedure for experienced surgeons in patients with RCC with level 0 to II VTT.

Chromosome abnormality is one of the important causes of spontaneous abortion. However, due to regional and ethnic differences, the reported rates of chromosomal abnormalities in patients with spontaneous abortion vary greatly. At present, there is no large sample statistics of chromosome abnormality in patients with spontaneous abortion in Yantai, Shandong province, China and hence 2959 couples (5918 individuals) with spontaneous abortion were recruited for this study. G banding was used to examine the karyotype of patients. The results showed that chromosomal abnormalities were present in 173 of 2959 couples with the rate of 5.85%. Female carriers were significantly higher than male. Chromosomal abnormality rate was positively correlated with the number of spontaneous abortions. Structural aberrations were significantly greater than numerical aberrations, with a prevalence of 92.49% and 7.51%, respectively. Balanced translocation, Robertson translocation and inversion were the most common types of chromosomal structural abnormalities. Among them, the proportion of balanced translocation was the highest (63.13%, 101/160). In addition, three cases of rare complex abnormal karyotype were detected. In summary, chromosome abnormality could be one of the important causes of spontaneous abortion in Yantai, Shandong province, China. The sex of patients with chromosomal abnormalities and the number of spontaneous abortions should be considered in genetic counselling. When one of the partners have chromosome abnormality, preimplantation genetic diagnosis and prenatal diagnosis could play a great significance for preventing the birth of children with chromosomal diseases and reducing birth defects.

Background. The present research focuses on preeclampsia (PE), a clinically relevant pregnancy disease. To date, the majority of research on PE was centered on placental insufficiency. However, the genes that regulate these processes, and the exact molecular mechanisms modulating these processes, are still unclear. Methods. We obtained placentae from a clinically well-specified group of patients with preeclampsia and gestationally matched control pregnancies in order to evaluate the expression of homeobox gene DLX3 by immunohistochemical staining, real-time PCR, and Western immunoblotting and determine the function of DLX3 utilizing lentivirus transfection in HTR-8/SVneo cells. Results. In the present study, we detected DLX3 expression in a clinically well defined cohort of preeclampsia-affected and gestation-matched control pregnancies. As opposed to the controls, DLX3 was overexpressed in preeclampsia-affected placentae. Moreover, we found that the in vitro cell growth and invasive ability of HTR8/SVneo cells was enhanced by the exogenous overexpression of DLX3 ( P < 0.05 ). It can be seen that DLX3 influences the cell cycle of HTR-8/SVneo cells in vitro. Conclusions. DLX3 has been shown to be strongly related to normal placental growth as well as the pathophysiology of preeclampsia. The imbalanced expression of DLX3 may perform an integral function in the occurrence and progression of preeclampsia.

Sodium/iodide symporter (NIS) acts as a vital role in regulation of iodide uptake in thyroid cancer. However, the efficient approach to increase NIS expression and the mechanism of NIS-mediated iodide uptake in thyroid cancer remain unclear.Small activating RNA (saRNA) was used to promote NIS expression. And the cell viability, apoptosis, and autophagy were detected using Cell count-kit 8 (CCK-8), Annexin V-FITC/PI double staining, and GFP-LC3 immunofluorescence assays, respectively. The protein levels of caspase 3, Bax, Bcl-2, ATG5, ATG12, LC3B Ⅱ to LC3B Ⅰ, Beclin 1, P62, AMPK, mTOR, P70S6K, actin, and phosphorylation of AMPK, mTOR, P70S6K were determined by western blotting. Moreover, a nude murine node with transplanted NC-dsRNA or NIS-482-transfected SW579 cells was used to examine the effect of NIS-mediated autophagy in vivo. And the levels of caspase 3 and ki67 were examined by immunohistochemical staining assay.saRNA mediated NIS mRNA and protein upregulated in SW579 cells. saRNA-mediated NIS expression inhibited cell proliferation, induced apoptosis and autophagy, and promoted iodide uptake in SW579 cells. Moreover, the effects of NIS on cells were enhanced by autophagy activator Rapamycin whereas reversed by autophagy inhibitor 3-Methyladenine (3-MA). For mechanism analysis, we found that NIS upregulation exerted the effects on cell proliferation, apoptosis, autophagy, and iodide uptake via regulating AMPK/mTOR pathway. We also demonstrated that saRNA-mediated NIS expression promoted iodide uptake in vivo.saRNA-mediated NIS expression acted as a critical role in increasing iodide uptake via AMPK/mTOR pathway in thyroid cancer.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with differences in prevalence and severity among ancestral groups. This study was undertaken to identify novel genetic components, either shared by or distinct between Asian and European populations.Both trans-ancestral and ancestry-specific meta-analyses of genome-wide association studies (GWAS) for SLE were performed, involving 30,604 participants of European, Chinese, or Thai origin. Using public epigenomic data and expression quantitative trait loci, fine-mapping analyses were conducted to identify putative causal variants and genes for the newly identified loci. Performance of polygenic risk scores for the Thai cohort was evaluated by comparing different training data.A 1-bp deletion upstream of IFNLR1 was found to be associated with SLE, with the risk allele correlated with increased expression of IFNLR1. This gene encodes interferon-λ (IFNλ) receptor 1, providing evidence of a role of type III IFN signaling in SLE. An intronic variant in SLC29A3 was found to be associated with SLE in Asians only. The putative risk variant may modulate SLC29A3 expression in a monocyte-specific manner. SLC29A3 encodes a lysosomal nucleoside transporter, and subsequent analyses suggested that reduced lysosomal function and phagocytosis might be the mechanism underlying this association. Ancestry-shared loci in or near TAOK3, CHD9, CAMK1D, ATXN1, and TARBP1 and Asian-specific loci close to PEX2, FCHSD2, and TMEM116 also reached the genome-wide significant association with SLE. In addition, trans-ancestral meta-analysis was shown to be valuable in risk prediction for individuals without ancestry-matched data.In this study both shared and Asian-specific loci for SLE were identified, and functional annotation provided evidence of the involvement of increased type III IFN signaling and reduced lysosomal function in SLE.

Histone deacetylase 4 (HDAC4) is a member of the HDACs family, its expression is closely related to the cell development. The cell is an independent living entity that undergoes proliferation, differentiation, senescence, apoptosis, and pathology, and each process has a strict and complex regulatory system. With deepening of its research, the expression of HDAC4 is critical in the life process. This review focuses on the posttranslational modification of HDAC4 in cell biology, providing an important target for future disease treatment.

BackgroundTotal joint arthroplasty (TJA), including total knee arthroplasty (TKA) and total hip arthroplasty (THA), is required for many patients. This study aimed to evaluate the medical costs, length of stay (LOS), blood transfusion and in-hospital complications in patients undergoing simultaneous and staged TJA.MethodsAll patients who underwent primary bilateral TJA from 2013 to 2018 in our institute were included. The propensity score matching analysis was performed between simultaneous and staged TJA patients. The difference in medical costs, LOS, blood transfusion and in-hospital complications was compared between simultaneous and staged groups.ResultsExcept for materials fees and general therapy fees, medical costs (bed fees, general therapy fees, nursing care fees, check-up and laboratory test fees, surgical fees and drug fees) were significantly lower in the simultaneous TKA, THA and TJA group. The total average medical costs in simultaneous and staged TKA groups were $15 385 and $16 729 (pConclusionsOur results indicate that simultaneous TKA and THA with a shorter LOS would cost fewer (costs incurred during hospitalisation) than staged TKA and THA. Complication rates were not affected by the choice for staged or simultaneous arthroplasty, but the incidence of blood transfusion was higher in the simultaneous groups.

Digital technology has promoted service innovation and provided effective technical support for public service innovation in recent years. Smart healthcare, a key element of smart city development, has gradually become an important issue in government administration. Digital technology is deeply embedded in healthcare services and reshapes value creation through digital transformation. This study combines data-enabled platform business models and value cocreation and adopts a case study approach to develop a business model for a medical information service platform that allows stakeholders to cocreate value through service exchange and resource integration in smart healthcare ecosystems, promotes efficient and coordinated applications of information, and realizes innovative development in the medical industry.

Objective We investigated the safety and effectiveness of a modified transabdominal approach for renal cell carcinoma (RCC) with a supradiaphragmatic inferior vena cava (IVC) tumor thrombus (TT). Methods Eight patients underwent radical nephrectomy with removal of a supradiaphragmatic IVC-TT through an abdominal incision using a transdiaphragmatic approach in Peking University Third Hospital from April 2015 to January 2018. We modified this technique using a Foley catheter balloon to avoid piggyback liver mobilization. Results All patients underwent successful operations. The median operative time was 7 hours 23 minutes. The median estimated blood loss was 2963 mL. All patients received a blood transfusion with a median blood infusion volume of 2162 mL. Two patients with Budd–Chiari syndrome developed postoperative ascites and hydrothorax due to non-watertight repair of the diaphragm. During a follow-up of 11 to 44 months, only one patient died of liver metastasis and four patients developed distant metastasis without recurrence in the IVC. Conclusions The modified transabdominal approach described herein has an encouraging safety profile and provides a surgical option for treatment of RCC with a supradiaphragmatic IVC-TT. More evidence concerning the beneficial role of this procedure will be elucidated in further studies.

Acute lung injury (ALI) is a pulmonary disorder, which can result in fibrosis of the lung tissues. Recently, mesenchymal stem cell (MSC) has become a novel therapeutic method for ALI. However, the potential mechanism by which MSC regulates the progression of ALI remains blurry. The present study focused on investigating the mechanism underneath MSC-reversed lung injury and fibrosis. At first, we determined that coculture with MSC led to the inactivation of NF-κB signaling and therefore suppressed hedgehog pathway in LPS-treated MLE-12 cells. Besides, we confirmed that MSC-exosomes were responsible for the inhibition of EMT process in LPS-treated MLE-12 cells through transmitting miRNAs. Mechanism investigation revealed that MSC-exosome transmitted miR-182-5p and miR-23a-3p into LPS-treated MLE-12 cells to, respectively, target Ikbkb and Usp5. Of note, Usp5 interacted with IKKβ to hamper IKKβ ubiquitination. Moreover, co-inhibition of miR-182-5p and miR-23a-3p offset the suppression of MSC on EMT process in LPS-treated MLE-12 cells as well as in LPS-injured lungs of mice. Besides, the retarding effect of MSC on p65 nuclear translocation was also counteracted after co-inhibiting miR-182-5p and miR-23a-3p, both in vitro and in vivo. In summary, MSC-exosome transmitted miR-23a-3p and miR-182-5p reversed the progression of LPS-induced lung injury and fibrosis through inhibiting NF-κB and hedgehog pathways via silencing Ikbkb and destabilizing IKKβ.

Purpose Proper aqueous humor (AH) dynamics is crucial for maintaining the intraocular pressure (IOP) in the eye. This study aims to investigate the function of Piezo2, a newly discovered mechanosensitive ion channel, in regulating AH dynamics. Methods Immunohistochemistry (IHC) analysis and western blotting were performed to detect Piezo2 expression. The Cre-lox system was applied to create a conditional knockout model of Piezo2. IOP and aqueous humor outflow facility in live animals were recorded with a Tonometer and a syringe-pump system for up to 2 weeks. Results We first detected Piezo2 with robust expression in the human trabecular meshwork (TM), Schlemm’s canal (SC), the ciliary body’s epithelium, and ciliary muscle. In addition, we found Piezo2 in human retinal ganglion cells (RGCs) and astrocytes in the optic nerve head (ONH). Through the Cre-lox system, Piezo2 can be successfully downregulated in mouse iridocorneal angle tissues. However, Piezo2 downregulation cannot significantly influence the IOP and outflow facility through the conventional pathway. Instead, we observed an effect of downregulated Piezo2 on decreasing the intercept in the flow rate versus pressure plot. According to the Goldmann equation, Piezo2 may function in regulating unconventional outflow, AH production, and episcleral venous pressure. Conclusions These findings, for the first time, demonstrate that Piezo2 acts as an essential mechanosensor in maintaining the proper aqueous humor dynamics in the eye.

Background Total Healthcare Expenditure (THE) has increased substantially in all countries. Since the health system reform and health policy environment differ from each country, it is necessary to analyze the motivations of THE in a specific country. Methods The objective of this study was to analyze the influential factors of Provincial THE (PTHE) per capita in China by using spatiotemporal panel data across 31 provinces (including provinces, autonomous regions, and municipalities, all called provinces in here) from 2009 to 2016 at the provincial and annual level. Generalized Estimating Equation (GEE) was used to identify the influential factors of PTHE per capita. Results The number of beds per 10,000 population explained most of the variation of PTHE per capita. The results also showed that health expenditure in China reacts more to mortality compared with the Gross Domestic Product (GDP) per capita. But mortality and Out-Of-Pocket Payments (OOP) as a percentage of THE were associated with PTHE per capita negatively. The rate of infectious diseases and THE as a percentage of GDP had no statistical significance. And the Proportion of the Population Aged 65 and Over (POP65) impact PTHE per capita positively. But the coefficient was small. Conclusions In response to these findings, we conclude that the impact of the increasing percentage of OOP in THE diminishes the PTHE. Furthermore, we find that both the “baseline” health level and health provision are positively correlated with PTHE, which outweighs the effect of GDP.

M2-like tumour-associated macrophages (TAMs) have been demonstrated to promote the growth of anaplastic thyroid carcinoma (ATC). However, the underlying mechanism of M2-like TAMs in ATC remains unclear. Thus, in the present study, the role and mechanism of M2-like TAMs in ATC were investigated. M2-like TAMs were induced by treatment with PMA, plus IL-4 and IL-13, and identified by flow cytometry. Transwell and sphere formation assays were applied to assess the invasion and stemness of ATC cells. The expression levels of insulin-like growth factor (IGF)-1 and IGF-2 were examined by ELISA and reverse transcription-quantitative PCR. Proteins related to the epithelial-mesenchymal transition (EMT), stemness and the PI3K/AKT/mTOR pathway were examined via western blotting. Immunohistochemistry (IHC) was used to detect the expression of the M2-like TAM markers CD68 and CD206 in ATC tissues and thyroid adenoma tissues. It was found that treatment with PMA plus IL-4 and IL-13 successfully induced M2-like TAMs. Following co-culture with M2-like TAMs, the invasive ability and stemness of ATC cells were significantly increased. The expression levels of the EMT-related markers N-cadherin and Vimentin, the stemness-related markers Oct4, Sox2 and CD133, and the insulin receptor (IR)-A/IGF1 receptor (IGF1R) were markedly upregulated, whereas E-cadherin expression was significantly decreased. In addition, the production of IGF-1 and IGF-2 was significantly increased. Of note, exogenous IGF-1/IGF-2 promoted the invasion and stemness of C643 cells, whereas blocking IGF-1 and IGF-2 inhibited metastasis and stemness by repressing IR-A/IGF-1R-mediated PI3K/AKT/mTOR signalling in the co-culture system. IHC results showed that the expression of CD68 and CD206 was obviously increased in ATC tissues. To conclude, M2-like TAMs accelerated the metastasis and increased the stemness of ATC cells, and the underlying mechanism may be related to the section of IGF by M2-like TAMs, which activates the IR-A/IGF1R-mediated PI3K/AKT/mTOR signalling pathway.

Objective: Studies were conducted to develop and validate the Capacity for Psychotherapy Process Scale (CFPPS), a self-rating measure of capacity for the psychotherapy process from a trans-theoretical perspective. Method: In Study 1, a two-round Delphi methodology consulting 27 and 15 experts, respectively, was used to select items and identify content validity. In Study 2, 279 clients were recruited for exploratory factor analysis (EFA). In Study 3, confirmatory factor analysis and internal consistency analysis were conducted among 390 outpatients; the discriminant validity and predictive validity were studied in 270 outpatients and 82 psychotherapy outpatients, respectively. Results: The Delphi method resulted in 52 items. Through EFA, the CFPPS was reduced to 20 items, focusing on five factors: motivation, belief, self-revelation, persistence, and insight; the internal consistencies were good (0.92 for total scale and 0.82-0.91 for the factors). The CFPPS was not or was only weakly associated with symptoms. The Bonferroni-corrected partial correlation analyses revealed that the CFPPS was positively related to working alliance and session impact. Conclusions: The CFPPS is a preliminary step toward the self-report assessment of the capacity for psychotherapy process from a trans-theoretical perspective and may potentially be used to predict the working alliance and session impact.

Acute respiratory distress syndrome (ARDS) develops rapidly and has a high mortality rate. Survivors usually have low quality of life. Current clinical management strategies are respiratory support and restricted fluid input, and there is no suggested pharmacological treatment. Mesenchymal stromal cells (MSCs) have been reported to be promising treatments for lung diseases. MSCs have been shown to have a number of protective effects in some animal models of ARDS by releasing soluble, biologically active factors. In this review, we will focus on clinical progress in the use of MSCs as a cell therapy for ARDS, which may have clinical implications during the coronavirus disease 2019 (COVID-19) pandemic.

Aims This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. Materials and methods Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/β-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. Key findings M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and β-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. Significance ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/β-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.

Background: Practice guidelines have recommended cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) as the treatment of choice for major depression disorder (MDD). However, whether one therapy is better than the other remains inconclusive. The aim of this study was to compare the treatment efficacy of the two treatment approaches for MDD. Methods: Using the terms “cognitive behavior therapy or cognitive therapy or CBT or CT or cognitive behavioral therapy” and “interpersonal psychotherapy or IPT,” we systematically searched PubMed, Psyclnfo and Chinese National Knowledge Infrastructure databases up to February 2017. The language was restricted to be English and Chinese. Therapeutic outcomes, characteristics, and research quality were then extracted and analyzed independently. In accessing the included studies, we followed the criteria suggested by the Cochrane Handbook for Systematic Reviews of Interventions. Results: Data for 946 patients from 10 randomized controlled trials were included in the study. Methodological quality was not optimal in most trials. Meta-analysis showed a mean difference (MD) of −1.31, 95% confidence interval (CI) (−2.49, −0.12) (P < 0.05) in favor of CBT according to the Beck Depression Inventory (BDI), and however, we did not found any statistically significant difference between CBT and IPT on the Hamilton Rating Scale for depression (HRSD) (MD −0.90, 95% CI [−2.18, 0.38]). Subgroup analyses for the studies in which patients were treated only by psychotherapy (MD −1.26, 95% CI [−2.78, 0.35]) and for those which offered more sessions of therapies (MD −0.82, 95% CI [−2.23, 0.59]) showed there was no significant difference between CBT and IPT according to BDI. Conclusions: Differences in treatment efficacy seem to vary according to different outcome measures. CBT shows an advantage over IPT for MDD according to BDI, and there is no significant difference between the two according to HRSD. These results should be interpreted with caution.

Objective: To present molecular cytogenetic characterization of mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p12-q21.13 associated with congenital hypoplasia of the tongue and review of the literature. Case report: A 27 year-old woman presented with congenital hypoplasia of the tongue. The chromosome karyotype of peripheral blood lymphocytes was detected by conventional cytogenetic analysis. The genome copy number variations were detected by SNP array. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,+mar[60]/46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636–81,263,140) × 2–3. Conclusion: With this study a patient involving mosaic trisomy 8p12-q21.13 along with clinical properties, is described and compared to previously reported cases involving a small supernumerary marker chromosome (sSMC) derived from chromosome 8. Keywords: Small supernumerary marker chromosome (sSMC), Chromosome 8, SNP array

Aims Chemotherapy and molecularly targeted therapy are main strategies for treatment of cancers. However, long-term treatment makes cancer cells acquire resistance to anti-cancer drugs, which severely limits the effects of cancer treatment. NcRNAs, especially miRNAs and lncRNAs, have been reported to play key roles in drug resistance and could restore drug responses in resistant cells. Main methods We presented a network-based framework to systematically identify drug resistance associated miRNAs and lncRNAs. First, we constructed a comprehensive heterogeneous miRNA-lncRNA regulatory network through integrating curated miRNA regulations to lncRNA, and significantly co-expressed miRNA-miRNA, lncRNA-lncRNA and miRNA-lncRNA interactions for each cancer type. Second, random walk with restart (RWR) was utilized to identify novel drug resistance associated ncRNAs. Key findings We predicted 470 associations of 34 miRNAs and 79 lncRNAs for 27 drugs in 10 cancer types. In addition, leave-one-out cross validation (LOOCV) demonstrated the effectiveness of the proposed approach. Next, we also demonstrated that the integrated heterogeneous cancer-specific network achieved better performance than the general curated miRNA-lncRNA regulatory network. What's more, we found that the drug resistance associated ncRNAs validated by high-throughput technology was also a reliable source for prediction. Significance We proposed a new framework to identify novel and reliable drug resistance associated ncRNAs, which provides new perspectives for drug resistance mechanism and new guidance for clinical cancer treatment.

Thrombocytopenia may be caused by diseases of various organ systems, especially the blood system. Certain drugs may also cause thrombocytopenia. In addition, it can result from various causes of pseudo-reduction. Therefore, a correct understanding of the causes of thrombocytopenia and their underlying mechanisms has important significance for clinical diagnosis and treatment. This study aimed to report a case of a 68-year-old woman with left upper abdominal mass and loss of appetite. The auxiliary examination showed splenomegaly and thrombocytopenia. The clinician planned to perform splenectomy. However, the laboratory physician considered that thrombocytopenia might be ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP). After effective communication between laboratory physicians and clinicians, the patient was diagnosed with splenic hyperfunction and pseudothrombocytopenia, and finally saved from undergoing splenectomy. The patient has a good prognosis after oral medication. Thrombocytopenia in this patient is caused by both hypersplenism and EDTA antagonism which is different from a single factor in other reports. The diagnosis of hematological abnormality may be challenging for physicians, especially thrombocytopenia. Therefore, medical staff should possess a rigorous working style and a high sense of responsibility besides maintaining high professional quality. Further, they should actively, timely, and effectively communicate with auxiliary departments to avoid misdiagnosis and missed diagnosis.

In this paper, we expound the origin and development of special acupuncture needle tools for cutaneous region, and discuss its mechanisms from modern medical theory. By consulting related acupuncture books and literature and in combination with needles used in clinical practice, we conclude that acupuncture needle tools can be divided into skin massage needle (digital pressing, spoon needle, etc.), cutaneous pricking blood needle (shear needle, three-edged needle, plum blossom needle, etc.), subcutaneous shallow puncture needle (intradermal needle, superficial needle, subcutaneous in-dwelling needle), etc. The skin-brain axis is the core of skin stimulation therapy. Mechanical pressure exerted on the skin surface induced by acupuncture stimulation or pressing, microcirculation changes and drug superposition are probably the underlying mechanisms of special skin acupuncture needle tools for treatment of various clinical disorders.

The physicochemical properties of nanoparticles play critical roles in regulating nano-bio interactions. Whereas the effects of the size, shape, and surface charge of nanoparticles on their biological performances have been extensively investigated, the roles of nanoparticle mechanical properties in drug delivery, which have only been recognized recently, remain the least explored. This review article provides an overview of the impacts of nanoparticle mechanical properties on cancer drug delivery, including (1) basic terminologies of the mechanical properties of nanoparticles and techniques for characterizing these properties; (2) current methods for fabricating nanoparticles with tunable mechanical properties; (3) in vitro and in vivo studies that highlight key biological performances of stiff and soft nanoparticles, including blood circulation, tumor or tissue targeting, tumor penetration, and cancer cell internalization, with a special emphasis on the underlying mechanisms that control those complicated nano-bio interactions at the cellular, tissue, and organ levels. The interesting research and findings discussed in this review article will offer the research community a better understanding of how this research field evolved during the past years and provide some general guidance on how to design and explore the effects of nanoparticle mechanical properties on nano-bio interactions. These fundamental understandings, will in turn, improve our ability to design better nanoparticles for enhanced drug delivery.

By analyzing the evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle recorded in ancient literature of traditional Chinese medicine, it is found that the main contents of reinforcing-reducing manipulation by lifting and thrusting the needle include manipulating speed change, manual amplitude, insertion layer, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity. Among them, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity are the unnecessary parameters, while the manipulating speed change, manual amplitude and insertion layer are the indispensable parameters. The manipulating speed change is the core of the necessary parameters for the reinforcing-reducing manipulation achieved by lifting and thrusting the needle. Combined with the manual amplitude, the manipulating speed of needle determines the volume of needling stimulation. The insertion layer is decided on the base of the clinical demand. In the core technique of reinforcing-reducing manipulation by lifting and thrusting the needle, the reinforcing is achieved by thrusting the needle forcefully and quickly and then lifting the needle body slowly and evenly back to the original layer. The reducing is achieved by lifting the needle forcefully and quickly and then thrusting the needle body slowly and evenly back to the original layer. The manipulating speed and manual amplitude of needling are the parameters to quantize acupuncture manipulation. In association with the acupuncture effects in human body, these parameters contribute to the interpretation of the dose-effect relationship of acupuncture and the improvement of clinical effects.

Objective Acinetobacter baumannii has become an important problem because of the high drug resistance rate. The aim of this study was to assess the antimicrobial resistance profile and explore the role of membrane porin in imipenem resistance of A baumannii. Methods A total of 63 isolates of imipenem‐resistant A baumannii (IRAB) and 21 of imipenem‐sensitive A baumannii (ISAB) were collected. Susceptibility testing to 16 kinds of antimicrobial agents was conducted by K‐B method. PCR technique was used to detect carO and oprD genes, and sequencing was performed to compare the sequence between IRAB and ISAB. Three‐dimensional structure model of CarO protein was established. Results While ISAB isolates presented sensitive to most classes of antibiotics, isolates of IRAB displayed much higher resistance rate except tigecycline (3.2%), cefoperazone/sulbactam (28.6%), and minocycline (30.2%). All 84 isolates were observed carrying both carO and oprD genes. Further sequencing revealed important mutations of carO gene existed in IRAB in comparison with ISAB. Meanwhile, significant differences in three‐dimensional structure of carO protein molecule were also found between IRAB and ISAB. Conclusions The drug resistance profile of IRAB is increasingly severe in clinical settings. Mutation of CarO was identified as one of the molecular mechanisms involved in imipenem resistance in A baumannii.

To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission (CR1).Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation（allo-HSCT）and underwent auto-PBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after auto-PBHSCT, the maintenance therapy with interleukin-2 (IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality (TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemia-free survival (LFS) rate at 2 years and 3 years, overall survival (OS) were evaluated at 3 years and 4 years.Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred, but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count (ANC)0.5×10Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.应用改良BU/CY方案预处理联合自体外周血造血干细胞移植治疗青年中、低危急性髓系白血病疗效观察.观察青年中、低危急性髓系白血病（AML）在第1次完全缓解期（CR1）接受白消安（BU）/环磷酰胺（CY）改良方案预处理后行自体外周血造血干细胞移植（auto-PBHSCT）的安全性及疗效。.采用回顾性分析方法探讨改良BU/CY预处理联合auto-PBSCT的疗效。本院2013年5月至2016年12月期间10例青年中、低危AML患者，无异基因干细胞移植条件、CR1期接受以改良的BU/CY方案预处理联合auto-PBSCT，移植后3个月开始白介素-2（IL-2）或IL-2+二盐酸组胺维持治疗18个月。观察预处理方案的毒副作用、造血恢复时间、移植后100 d及1年内死亡率、复发率、2年及3年无白血病生存率（LFS）、3年及4年总生存率（OS）。.常见的非血液学毒性反应为胃肠道反应（轻度7例、中度3例、重度1例）、轻度肝损害（4例）、出血性膀胱炎0例、轻中度感染10例（血流感染5例，肠道感染2例，肛周感染3例，口腔感染2例）。患者均达到清髓效果，中性粒细胞（ANC）0.5×10改良的BU/CY+auto-PBSCT治疗模式可达到清髓目的，对青年中、低危AML疗效明确，移植相关死亡率低，LFS及OS时间较长，可作为无异基因造血干细胞移植条件患者的另一个治疗选择。.

In this paper, we present an efficient robust labeling method for coronary arteries from X-ray angiograms based on energy optimization. The fundamental goal of this research is to facilitate the analysis and diagnosis of interventional surgery in the most efficient way, and such effort could also improve the performance during doctor training, and surgery simulation and planning. Compared to the prior state-of-the-art, our method is much more robust to resist noises and is tolerant to even incomplete data because of the “ built-in ” nature of global optimization. We start with a fully parallelized algorithm based on Hessian matrix to extract the tubular structure from the X-ray angiograms as vessel candidates. Then, instead of using the candidates directly, we use the grow cut (Vezhnevets and V. Konouchine, Growcut: Interactive multi-label N-D image segmentation by cellular automata, in Proc. of Graphicon, 2005, pp. 150–156.) method, which is similar to graph cut (Boykov et al. , Fast approximate energy minimization via graph cuts, IEEE Trans. Pattern Anal. Mach. Intell. , vol. 23, no. 11, pp. 1222–1239, Nov. 2001.)but with better performance to extract the precise vessel structure from the images. Next, we use the fast marching method with second derivatives and cross neighbors to extract the accurate skeleton segments. After that, we propose an efficient method based on iterative closest point (Z. Zhang, Iterative point matching for registration of free-form curves and surfaces, Int J. Comput. Vis. , vol. 13, no. 2, pp. 119–152, 1994.) to organize the skeleton segments by treating the continuity and similarity as extra constraints. Finally, we formulate the vessel labeling problem as an energy optimization problem and solve it using belief propagation. We also demonstrate several typical applications including flow velocity estimation, heart beat estimation, and vessel diameter estimation to show its practical uses in clinical diagnosis and treatment. Our experiments exhibit the correctness and robustness, as well as the high performance of our algorithm. We envision that our system would be of high utility for diagnosis and therapy to treat vessel-related diseases in a clinical setting in the near future.

The size and shape of a nodule are the essential indicators of malignancy in lung cancer diagnosis. However, effectively capturing the nodule's structural information from CT scans in a computer-aided system is a challenging task. Unlike previous models that proposed computationally intensive deep ensemble models or three-dimensional CNN models, we propose a lightweight, multiple view sampling based multi-section CNN architecture. The model obtains a nodule's cross sections from multiple view angles and encodes the nodule's volumetric information into a compact representation by aggregating information from its different cross sections via a view pooling layer. The compact feature is subsequently used for the task of nodule classification. The method does not require the nodule's spatial annotation and works directly on the cross sections generated from volume enclosing the nodule. We evaluated the proposed method on lung image database consortium (LIDC) and image database resource initiative (IDRI) dataset. It achieved the state-of-the-art performance with a mean 93.18% classification accuracy. The architecture could also be used to select the representative cross sections determining the nodule's malignancy that facilitates in the interpretation of results. Because of being lightweight, the model could be ported to mobile devices, which brings the power of artificial intelligence (AI) driven application directly into the practitioner's hand.

Arkadia is able to degrade key signaling molecules in the transforming growth factor (TGF)-β1 signaling pathway; however, the expression of Arkadia in the liver during development and progression of TGF-β1/Smad signaling-regulated hepatic fibrosis remains to be elucidated. The present study aimed to examine Arkadia expression in the livers of two rat models of hepatic fibrosis induced by bile duct ligation and carbon tetrachloride intoxication, and in human liver samples from patients with hepatic fibrosis. Expression was analyzed by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. The results indicated that Arkadia was predominantly expressed in the cytoplasm of cholangiocytes and hepatocytes. The protein expression levels of Arkadia were significantly decreased in fibrotic livers, whereas the mRNA expression levels of Arkadia were significantly increased in fibrotic livers compared with in nonfibrotic livers. In conclusion, these data indicated that Arkadia may regulate the pathogenesis and progression of hepatic fibrosis.

Introduction Difficult removal of locking plates including less invasive stabilisation systems (LISSs) and locking compression plates (LCPs) sometimes occur. However, investigations of the mechanisms and correlated factors of complicated removal remain scant. This study aims to identify correlated factors for the difficult removal of locking plates and to propose suggestions for decision making regarding implant removal and the prevention of complicated removal. Materials and methods In total, 308 consecutive patients who underwent LCP/LISS removal from Sep. 2004 to Nov. 2013 were assessed. Using the Mann–Whitney U test, we analysed the correlation between difficult removal and the duration between open reduction and internal fixation (ORIF) and implant removal as well as the correlation between difficult removal and the patients’ age. Using Chi Square test, we assessed the correlations between complicated removal and the size, location, insertion technique and cortical purchase of the locking head screw (LHS). Correlated factors were separately determined in upper and lower extremities. Rates of difficult removal in different fracture locations were evaluated, and postoperative complications were documented. Results Of the total 308 patients, thirty-seven had intra-operative difficulties, and six patients experienced postoperative complications. Six out of fifteen patients with peri-elbow fractures and five out of seventeen patients with femur fractures suffered difficult removal, while four out of one hundred patients with malleolar fractures had intra-operative difficulties. Difficulties were experienced with 30 of 338 LCPs, 7 of 32 LISSs, 67 of 1533 small-diameter (≤3.5-mm) LHSs, and 12 of 442 large-diameter (≥4.5-mm) LHSs. Three LCPs and seventeen small-diameter LHSs were retained. A longer interval between ORIF and removal, younger age and bicortical screws correlated with difficult removal in the upper extremities, and a longer duration before removal, small-diameter LHS and minimally invasive insertion of LHS were predictors in the lower extremities. Conclusions Complications occur with LCP/LISS removal, and it should not be a routine procedure. If removal is indicated, performing surgery as soon as radiographs show fracture healing is recommended. Different considerations should apply when making decisions and removing implants from patients with different fracture sites.

Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Migration of the activated HSCs to the site of injury is one of the key characteristics during the wound healing process. We have previously demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) is involved in migration and lamellipodia formation of HSCs. However, the role of PHP14 in liver fibrosis remains unknown. In this study, we first assessed PHP14 expression and distribution in liver fibrotic tissues using western blot, immunohistochemistry, and double immunofluorescence staining. Next, we investigated the role of PHP14 in liver fibrosis and, more specifically, the migration of HSCs by Transwell assay and 3D collagen matrices assay. Finally, we explored the possible molecular mechanisms of the effects of PHP14 on these processes. Our results show that the PHP14 expression is up-regulated in fibrotic liver and mainly in HSCs. Importantly, TGF-β1 can induce PHP14 expression in HSCs accompanied with the activation of HSCs. Consistent with the previous study, PHP14 promotes HSCs migration, especially, promotes 3D floating collagen matrices contraction but inhibits stressed-released matrices contraction. Mechanistically, the PI3Kγ/AKT/Rac1 pathway is involved in migration regulated by PHP14. Moreover, PHP14 specifically mediates the TGF-β1 signaling to PI3Kγ/AKT pathway and regulates HSC migration, and thus participates in liver fibrosis. Our study identified the role of PHP14 in liver fibrosis, particularly HSC migration, and suggested a novel mediator of transducting TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway.PHP14 is up-regulated in fibrotic liver and activated hepatic stellate cells. The expression of PHP14 is induced by TGF-β1. The migration of hepatic stellate cells is regulated by PHP14. PHP14 is a mediator of TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway in hepatic stellate cells.

The aim of the present study was to investigate the role of the angiotensin-converting enzyme (ACE)2-angiotensin‑(Ang)-(1-7)-Mas axis in the pathogenesis of pancreatitis and the association between this axis and the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor (NF-κB) signaling pathway in pancreatic acinar cells. Mouse pancreatic acinar cancer (MPC-83) cells were stimulated with 10 nM caerulein (CAE) to create an in vitro model of acute pancreatitis, and collected for analysis at 2, 6, 12, 24 and 48 h post stimulation. In addition, cells were pretreated with different concentrations of Ang‑(1‑7), Ang‑(1‑7) antagonist A779, p38 MAPK inhibitor SB203580 or ACE2 inhibitor DX600 for 30 min, and then stimulated with CAE for 24 h. The ACE2, Mas receptor, p38 MAPK, phosphorylated (p)-p38 MAPK and NF-κB expression levels were evaluated using western blotting and immunofluorescence. p38 MAPK, NF-κB, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8 and IL-10 mRNA expression levels were assessed using reverse transcription-quantitative polymerase chain reaction. The results of the immunofluorescence assay demonstrated that ACE2 and p38 MAPK were present mainly in the cytoplasm, while the Mas receptor was located mainly in the cell membrane. ACE2, p38 MAPK and p-p38 MAPK protein levels were significantly increased (P

Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time-consuming, and often fail to replicate human activity. Here a microfluidic tumor-on-a-chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time-elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX-loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.

Recently, studies involving uterine cervical cancer and uterine corpus cancer have been reported from many institutes. The presence of regulatory T cells (Treg cells) in human uterine cancer is crucial for maintaining immunological homeostasis. To improve treatment strategies, I will be reviewing recent studies in the field. This work will discuss the central role that Treg cells play in the development of uterine cancer, which makes these cells a key missing component in current cancer immunotherapy.

In this paper, 17 compounds (1–17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4’-O-β-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).

We report our initial experience with the first series of laparoendoscopic single-site (LESS) radical cystectomy and urinary diversion performed by a single surgeon using a homemade single-port device at a single institution in China.Between December 2010 and February 2011, we performed five LESS radical cystectomis using a homemade single-port device composed of an inverted cone device of polycarbonate and a powder-free surgical glove. The port was placed into a 5-cm periumbilical incision. The conventional laparoscope and laparoscopic instruments were inserted through the single-port. No additional ports were needed for radical cystoprostatectomy and bilateral standard pelvic lymphadenectomy. Cutaneous ureterostomy and ileal conduit urinary diversion were used for our patients, respectively. Perioperatively, oncologic data and complications were collected and analyzed.All the procedures were completed successfully. The mean extirpative operative time was 208.2 (168-280) minutes, estimated blood loss was 270 (100-500) mL, bowel recovering time was 9.75 (6-12) days, and postoperative hospital stay was 19.5 (14-28) days. One patient needed a transfusion of 400 mL of red blood cells. The pathologic evaluation revealed negative margins and negative lymph node involvement. After the operations, one patient had a bowel obstruction, while another patient died from cardiac disease. Mean follow-up time was 143 (110-173) days.In our experience, LESS radical cystectomy is clinically feasible and safe for selected patients, but requires a learning curve. Our homemade single-port device is a cost-effective and convenient device. Although the initial outcomes have been promising, the long-term oncologic evaluation of these patients awaits.

ObjectivesInterleukin 21 (IL-21) and IL-12 have been known to be effective antitumor agents. In this study, we evaluated whether IL-21 in combination with IL-12 could enhance the cytotoxicity of peripheral blood mononuclear cells (PBMCs) in patients with cervical intraepithelial neoplasia III and cervical cancer.MethodsPeripheral blood mononuclear cells were isolated from peripheral blood of cervical intraepithelial neoplasia III patients (n = 17) and cervical cancer patients (n = 18). Peripheral blood mononuclear cells were cultured with IL-2 in low concentration as control group. Interleukin 2–stimulated PBMCs were cocultured with anti–human IL-21 neutralizing antibody, IL-21 alone, IL-12 alone, and IL-21 plus IL-12, respectively, as test groups. The cytotoxicity of PBMCs against SiHa tumor cells was examined by lactate dehydrogenase released assay. CD4+CD25+FOXP3+ T regulatory (Treg) cells and CD4+IL-17A+ T helper 17 (TH17) cells were analyzed by flow cytometry. Proliferation and apoptosis were detected by CCK-8 (cell counting kit 8) assay and flow cytometry, respectively.ResultsCompared with controls, IL-21 and IL-12 significantly elevated PBMC cytotoxicity against SiHa cells. Moreover, IL-21 plus IL-12 significantly elevated PBMC cytotoxicity in comparison to IL-21 alone and IL-12 alone. We also found that IL-21 plus IL-12 significantly decreased Treg and TH17 cell proportion in comparison to controls. Notably, IL-21 plus IL-12 significantly decreased TH17 cell proportion in comparison to IL-21 alone. Both IL-21 and IL-12 significantly decreased the apoptosis rate of PBMCs, whereas neither IL-21 nor IL-12 had significant effect on PBMC proliferation.ConclusionsThe combination of IL-21 and IL-12 could efficiently stimulate PBMCs with cytotoxicity against SiHa cells, and the possible mechanisms may be due to down-regulated Treg and TH17 cell differentiation.

Objectives We present preliminary experience of retroperitoneal laparoscopic nephroureterectomy (RPLNU) with bladder cuff excision by combining cystoscopic resection with open transperitoneal dissection for native upper urinary tract transitional cell carcinoma (UUT-TCC) ipsilateral to a transplanted kidney. Methods Thirteen renal recipients with native UUT-TCC ipsilateral to a transplanted kidney were operated on with RPLNU between November 2005 and August 2008. Retroperitoneal laparoscopic nephrectomy was performed first and followed by cystoscopic excision of ipsilateral ureteral orifice with bladder cuff. A 6-cm midline lower abdominal incision was made. The distal ureter was dissected transperitoneally into the intramural segment, and the intact specimen was removed manually via the same incision. The cystostomy was generally not sutured. Results The mean operation time was 264 minutes. The mean estimated blood loss was 256 mL. Three patients needed blood transfusion. No open conversion was required. Two patients experienced minor complications. Pathologic findings confirmed UUT-TCC in all patients with 8 of the pelvis and 7 of the ureter. Four were involved with bladder TCC. With the mean follow-up of 30 months, none of the patients developed retroperitoneal recurrence or distant metastasis, 2 of the 4 patients with bladder TCC had recurrence in the bladder, and 2 had contralateral UUT-TCC after the first unilateral nephroureterectomy. Conclusions RPLNU with bladder cuff excision by combining cystoscopic resection with open transperitoneal dissection might be a safe and feasible alternative for native UUT-TCC ipsilateral to a transplanted kidney with acceptable oncological outcomes.