Calculation of additional load and deformation of the receiving well enclosure structure caused by shield tunneling.

The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

Sex Differences in Outcomes of Hepatobiliary and Pancreatic Surgery with Accelerated Rehabilitation.

BACKGROUND: Sex, in the sense of gender, is a major social demographic characteristic that has been shown to affect health care outcomes. The concept of enhanced recovery after surgery (ERAS) is an effective perioperative management measure that can reduce the perioperative stress response in patients. However, there are few studies on the differences between male and female patients under this type of care. We aimed to analyze sex differences in clinical characteristics among patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. METHODS: We enrolled patients who underwent liver, biliary tract, and gallbladder operations in the Department of Hepatobiliary and Pancreatic Surgery of Taizhou Hospital, Zhejiang Province, China, from April 2021 to July 2021. Key measures were collected for patients undergoing perioperative accelerated rehabilitation (i.e., the case group). The study group was assembled by performing 1:1 matching for age, sex, chronic disease, and type of surgery. Postoperative risk assessment, postoperative recovery indicators, and postoperative length of hospital stay (days) were compared between male and female patients. RESULTS: A total of 226 surgical patients were enrolled, including 109 male (48.23%) and 117 female patients (51.77%). The outcomes, presented as the median (min, max), were as follows: pulmonary rehabilitation risk assessment in females (1(0,3)) and males (0(0,2)), postoperative nausea and vomiting in females (2(1,3)) and males (1(0,2)), and time to first defecation in females (31(4,61)) and males (36(10,78)). Significant differences were indicated by p values < 0.05. CONCLUSION: We identified sex differences in the clinical prognosis and performance of perioperative patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. The perioperative pulmonary rehabilitation risk of male patients was higher than that of female patients, and the time to first defecation was longer in male than in female patients. The incidence of nausea and vomiting in women was higher than in men.

Effects of Different Heterogeneous Nutrient Environments on the Growth and Activities of Enzymes in the Roots of Fokienia hodginsii Families.

Currently, research on the F. hodginsii asexual lineage primarily focuses on the screening of growth traits and the control of single fertilizer applications. The effects of the heterogeneity of soil nutrients on root growth and activity have not been studied in detail. Therefore, we propose forest management measures to improve the foraging ability of forest trees in conjunction with stand productivity. In this experiment, annual containerized seedlings of 10 free-pollinated F. hodginsii lines from a primary asexual seed orchard were used as test subjects, and three heterogeneous nutrient environments of nitrogen (N), phosphorus (P), and potassium (K) were constructed. In contrast, homogeneous nutrient environments were used as the control to carry out potting experiments, to study the growth of F. hodginsii lines and the differences in the activities of root enzymes under the three heterogeneous nutrient environments, and to carry out the comprehensive evaluation using the principal component and cluster analysis method. The results were as follows: (1) The seedling height of F. hodginsii family lines under a homogeneous nutrient environment was significantly higher than that of all heterogeneous nutrient environments; the diameter of the ground was the highest under N heterogeneous nutrient environment and significantly higher than that of all the other nutrient environments; the biomass of the root system was the highest under P heterogeneous nutrient environment, which was significantly higher than that of homogeneous nutrient environment and K heterogeneous nutrient environment. The catalase (CAT) activity of F. hodginsii roots was higher than that of homogeneous nutrients in all heterogeneous nutrient environments but not significant, and the superoxide dismutase (SOD) activity was slightly higher than that of K heterogeneous and homogeneous nutrient environments in N and P heterogeneous nutrient environments. SOD activity was slightly higher than that of K heterogeneous and homogeneous nutrient environments under N, and P. peroxidase (POD) activity in the F. hodginsii root system was the highest under the P heterogeneous nutrient environment, which was significantly higher than that of the other nutrient environments. Unlike the activities of the enzymes, the content of malondialdehyde (MDA) in the roots of F. hodginsii was higher in the heterogeneous environment than in all the other nutrient environments. (2) Under N and P heterogeneous nutrient environments, lines 552 and 590 had higher seedling height, ground diameter, and root enzyme activity, while root biomass was highest in line 544; and under K heterogeneous nutrient environments, line 591 had higher seedling height, ground diameter, and root enzyme activity while root biomass was highest in line 551. In contrast to the patterns of seedling height, accumulation of root biomass and activities of root enzymes, family No. 590 had the highest ground diameter of all the F. hodginsii families under the heterogeneous nutrient environments. Family No. 547 had the highest MDA content. In conclusion, it can be seen that N heterogeneous and homogeneous nutrient environments can significantly increase the seedling height and diameter of F. hodginsii compared with P and K heterogeneous nutrient environments, and N and P heterogeneous nutrient environments can also increase the root biomass, root enzyme activities and significantly reduce the MDA content of F. hodginsii. According to the principal component analysis and cluster analysis, it can be seen that among the 10 F. hodginsii family lines, family lines 590 and 552 have higher evaluation in growth, root biomass accumulation, and enzyme activity.

Applicability of risk compensation to the relationship between health behaviors and COVID-19 vaccination among inpatients in Taizhou, China.

Aim: Based on the risk compensation theory, this study was designed to investigate the relationship between health behaviors of inpatients and COVID-19 vaccination during the epidemic with regard to the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taizhou, China. Subject and methods: We conducted an online self-administered survey with a group of inpatients in a grade III, class A hospital in Taizhou, China, from February 27, 2022, to March 8, 2022. A total of 562 complete questionnaires were collected, and 18 questionnaires completed in under 180 seconds were rejected, leaving a total of 544 (96.8%) valid questionnaires collected. The participants who had received a COVID-19 vaccine were asked to describe the differences in their health behaviors before and after the vaccination, and the data were analyzed using SPSS Statistics version 22.0 software. Results: There were significant differences in the percentage of individuals wearing masks (97.2% and 78.9%, P < 0.001) and the percentage of hand washing after taking off the mask (89.1% and 63.2%, P < 0.001) between the inoculated group and the uninoculated group; however, there were no significant differences in other health behaviors. The participants showed better health behaviors (handwashing and wearing a mask) after the vaccination than prior to it. Conclusions: Our findings suggest that the Peltzman effect did not increase risk behaviors during the Omicron epidemic. There was no reduction in health behaviors among inpatients after the COVID-19 vaccine, which may have even improved their health behaviors.

Response of the root morphological structure of Fokienia hodginsii seedlings to competition from neighboring plants in a heterogeneous nutrient environment.

Introduction: Critical changes often occur in Fokienia hodginsii seedlings during the process of growth owing to differences in the surrounding environment. The most common differences are heterogeneous nutrient environments and competition from neighboring plants. Methods: In this study, we selected one-year-old, high-quality Fokienia hodginsii seedlings as experimental materials. Three planting patterns were established to simulate different competitive treatments, and seedlings were also exposed to three heterogeneous nutrient environments and a homogeneous nutrient environment (control) to determine their effect on the root morphology and structure of F. hodginsii seedlings. Results: Heterogeneous nutrient environments, compared with a homogeneous environment, significantly increased the dry matter accumulation and root morphology indexes of the root system of F. hodginsii, which proliferated in nutrient-rich patches, and the P heterogeneous environment had the most significant enhancement effect, with dry matter accumulation 70.2%, 7.0%, and 27.0% higher than that in homogeneous and N and K heterogeneous environments, respectively. Homogeneous environments significantly increased the specific root length and root area of the root system; the dry matter mass and morphological structure of the root system of F. hodginsii with a heterospecific neighbor were higher than those under conspecific neighbor and single-plant treatments, and the root area of the root system under the conspecific neighbor treatment was higher than that under the heterospecific neighbor treatment, by 20% and 23%, respectively. Moreover, the root system under heterospecific neighbor treatment had high sensitivity; the heterogeneous nutrient environment increased the mean diameter of the fine roots of the seedlings of F. hodginsii and the diameter of the vascular bundle, and the effect was most significant in the P heterogeneous environment, exceeding that in the N and K heterogeneous environments. The effect was most significant in the P heterogeneous environment, which increased fine root diameter by 20.5% and 10.3%, respectively, compared with the homogeneous environment; in contrast, the fine root vascular ratio was highest in the homogeneous environment, and most of the indicators of the fine root anatomical structure in the nutrient-rich patches were of greater values than those in the nutrient-poor patches in the different heterogeneous environments; competition promoted most of the indicators of the fine root anatomical structure of F. hodginsii seedlings. According a principal component analysis (PCA), the N, Pm and K heterogeneous environments with heterospecific neighbors and the P heterogeneous environment with a conspecific neighbor had higher evaluation in the calculation of eigenvalues of the PCA. Discussion: The root dry matter accumulation, root morphology, and anatomical structure of F. hodginsii seedlings in the heterogeneous nutrient environment were more developed than those in the homogeneous nutrient environment. The effect of the P heterogeneous environment was the most significant. The heterospecific neighbor treatment was more conducive to the expansion and development of root morphology of F. hodginsii seedlings than were the conspecific neighbor and single-plant treatments.

Correlation between Serum ApoC III and Galectin-3 Levels and Maternal and Neonatal Adverse Outcomes in Gestational Diabetes Mellitus Patients.

Objective: The correlation between serum ApoC III and galectin-3 levels and adverse maternal and infant outcomes in GDM patients was analyzed. Methods: A total of 97 GDM patients admitted to our hospital from January 2019 to June 2021 were selected and divided into a good group and a poor group according to the pregnancy outcomes, ApoC III in blood of subjects was detected by immunoturbidimetry, and galectin-3 level was detected by enzyme-linked immunosorbent assay. Spearman correlation test was used to analyze the correlation between ApoC III and galectin-3 levels and pregnancy outcomes in patients with GDM, and ROC curves were drawn to analyze the value of each index alone and in combination to predict pregnancy outcomes in patients with GDM. Results: The levels of ApoC III and galectin-3 in the blood of the patients in the bad group were significantly higher than those in the good group, and the difference was statistically significant (t = 11.231, 14.965, P < 0.05). The levels of ApoC III and galectin-3 in the blood of GDM patients were significantly positively correlated with adverse pregnancy outcomes, and there was a statistical significance (r = 0.754 and r = 0.698, P < 0.05). The combined application of ApoC III and galectin-3 levels in GDM patients' blood to predict the adverse outcome of pregnancy was Log P = 0.623, ∗ ApoC III+0.605 ∗ galectin-3. The sensitivity, specificity, and AUC of combined application of ApoC III and galectin-3 for predicting adverse pregnancy outcomes in GDM patients were all greater than 90%, and AUC>0.90. The combined application in predicting adverse pregnancy outcomes were higher than those of the individual indicators, and the difference was statistically significant (P < 0.05). Conclusion: The levels of ApoC III and galectin-3 in the blood of GDM patients with adverse pregnancy outcomes were significantly increased, and the detection of ApoC III and galectin-3 could effectively improve the value of predicting adverse pregnancy in GDM.

Allele-aware chromosome-scale assembly of the allopolyploid genome of hexaploid Ma bamboo (Dendrocalamus latiflorus Munro).

Dendrocalamus latiflorus Munro is a woody clumping bamboo with rapid shoot growth. Both genetic transformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing techniques are available for D. latiflorus, enabling reverse genetic approaches. Thus, D. latiflorus has the potential to be a model bamboo species. However, the genome sequence of D. latiflorus has remained unreported due to its polyploidy and large genome size. Here, we sequenced the D. latiflorus genome and assembled it into three allele-aware subgenomes (AABBCC), representing the largest genome of a major bamboo species. We assembled 70 allelic chromosomes (2, 737 Mb) for hexaploid D. latiflorus using both single-molecule sequencing from the Pacific Biosciences (PacBio) Sequel platform and chromosome conformation capture sequencing (Hi-C). Repetitive sequences comprised 52.65% of the D. latiflorus genome. We annotated 135 231 protein-coding genes in the genome based on transcriptomes from eight different tissues. Transcriptome sequencing using RNA-Seq and PacBio single-molecule real-time long-read isoform sequencing revealed highly differential alternative splicing (AS) between non-abortive and abortive shoots, suggesting that AS regulates the abortion rate of bamboo shoots. This high-quality hexaploid genome and comprehensive strand-specific transcriptome datasets for this Poaceae family member will pave the way for bamboo research using D. latiflorus as a model species.

The complete chloroplast genome sequence of Bambusa albolineata (bambusodae).

Bambusa albolineata (local name: Hua Zhu) is found in Zhejiang, Jiangxi, Fujian, Taiwan, and Guangdong provinces of China, and is often cultivated on low hills, flatlands, and along streams and rivers. Due to its long internodes and flexible material, it is used as timber wood in China. In the current research, the complete chloroplast (CP) genome of B. albolineata was sequenced and reported for the first time. The complete CP genome sequence was 139,326 bp, including a large single-copy (LSC) region of 82,862 bp, a small single-copy (SSC) region of 12,870 bp, and a pair of invert repeats (IR) regions of 21,798 bp. Besides, the plastid genome consisted of 129 genes; having 82 protein-coding genes, 39 tRNA genes, and eight rRNA genes. The overall GC content of the genome was 44.2%. The phylogenetic analysis based on the complete chloroplast genome indicates that B. albolineata is strongly related to B. flexuosa and B. boniopsis.

The complete chloroplast genome sequence of Bambusa lapidea (Bambusodae).

Bambusa lapidea is primarily distributed in Guangdong, Guangxi, Sichuan, Yunnan, and Hong Kong in China, occurring on plains, lower hills, and wetlands on both sides of rivers and adjacent to villages. Therefore, we sequenced and reported the complete chloroplast genome of B. lapidea for the first time. The complete chloroplast genome sequence of B. lapidea was generated by de novo assembly using whole-genome next generation sequencing. The genome was 139,525 bp in total length, including a large next-copy (LSC) region of 83,034 bp, a small single-copy (SSC) region of 12,893 bp, a pair of invert repeats (IR) regions of 21,799 bp. The plastid genome contained 127 genes including 83 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on 14 chloroplast genomes indicates that B. lapidea is closely related to B. arnhemica sinospinosa and B. teres in Bambusodae.

The complete chloroplast genome sequence of Bambusa vulgaris cv. Wamin.

Bambusa vulgaris cv. Wamin is an attractive ornamental bamboo species of southern China. It has large swollen internodes and weeping culms, and it has considerable economic importance. In the present study, we sequenced the complete chloroplast genome of B. vulgaris cv. Wamin and reported it for the first time. The genome was 139,528 bp in total length, including a large single-copy (LSC) region of 83,038 bp, a small single-copy (SSC) region of 12,893 bp, and a pair of invert repeats (IR) regions of 21,799 bp. Plastid genome contained 138 genes, 82 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The overall GC content of the genome was 38.9%. The phylogenetic analysis based on the complete chloroplast genome reveals that B. vulgaris cv. Wamin is closely related to Bambusa teres. This research strengthens the genetic information of both the B. vulgaris cv. Wamin and the phylogenetic analyses of Gramineae.

A simple and feasible atom-precise biotinylated Cu(i) complex for tumor-targeted chemodynamic therapy.

A simple and feasible atom-precise biotinylated Cu(i) complex, which can catalyze H2O2 overexpressed commonly in the tumor microenvironment to produce ˙OH through a Fenton-like reaction, was prepared and employed as an effective agent for tumor-targeted chemodynamic therapy.

Complete chloroplast genome sequence of Gigantochloa verticillata (Bambusodae).

Gigantochloa verticillata is produced in Mengla and Jinghong, Yunnan Province, China, and cultivated in Hong Kong. Vietnam, Thailand, India, Indonesia, and Malaysia are distributed and cultivated. We determined the complete chloroplast genome sequence for G. verticillata using Illumina sequencing data. The complete chloroplast sequence is 139,489 bp, including large single-copy (LSC) region of 83,062 bp, small single-copy (SSC) region of 12,877 bp, and a pair of invert repeats (IR) regions of 21,775 bp. Plastid genome contain 132 genes, 85 protein-coding genes, 39 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on 23 chloroplast genomes indicates that G. verticillata is closely related to Dendrocalamus latiflorus in Bambusodae.

Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae.

We report a case of a 63-year-old female patient who developed a recurrent urinary tract infection (UTI) with extensively drug-resistant Klebsiella pneumoniae (ERKp). In the initial two rounds of phage therapy, phage resistant mutants developed within days. Although ERKp strains were completely resistant to sulfamethoxazole-trimethoprim, the combination of sulfamethoxazole-trimethoprim with the phage cocktail inhibited the emergence of phage resistant mutant in vitro, and the UTI of patient was successfully cured by this combination. Thus, we propose that non-active antibiotic and bacteriophage synergism (NABS) might be an alternative strategy in personalized phage therapy.

The complete chloroplast genome sequence of Bambusa beecheyana var.pubescens (Bambusodae).

Bambusa beecheyana var. pubescens is mainly distributed in South China to Southwest China, growing on hillsides or river banks. In the current study, we sequenced the complete chloroplast genome of B.beecheyana var. pubescens and reported for the first time. The genome is 139,402 bp in total length, include a large single-copy (LSC) region of 82,936 bp, small single-copy (SSC) region of 12,868 bp, a pair of invert repeats (IR) regions of 21,799 bp. Plastid genome contains 132 genes, 85 protein-coding genes, 39 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on 25 chloroplast genomes indicates that B. beecheyana var. pubescens is closely related to Bambusa oldhamii, Bambusa ventricosa and Bambusa ventricosa multiplex in Bambusodae.

Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-κB to repress autocrine STAT3 activation in chronic lymphocytic leukemia.

Coculture of nurse-like cells (NLCs) with chronic lymphocytic leukemia (CLL) cells induced leukemia cell phosphorylation of STAT3 (pSTAT3), which could be blocked by anti-Wnt5a antibodies or the anti-ROR1 monoclonal antibody, cirmtuzumab. Time-course studies revealed Wnt5a could induce activation of NF-κB within 30 minutes, but required more than 3 hours to induce pSTAT3. Culture of isolated CLL cells for 24 hours revealed Wnt5a-induced expression of interleukin 6 (IL-6), IL-8, CCL2, CCL3, CCL4, and CXCL1, which in turn could induce pSTAT3 in unstimulated CLL cells within 30 minutes. We found that Wnt5a could induce CLL cell expression of NF-κB target genes, including IL-6, and that this effect could be blocked by cirmtuzumab or drugs that inhibit NF-κB. Examination of CLL cells and plasma collected from patients treated with cirmtuzumab revealed reduced levels of phosphorylated p65 and diminished expression of NF-κB and STAT3 target genes in CLL cells, as well as lower plasma levels of IL-6, in the samples after therapy. Collectively, these studies indicate that Wnt5a/ROR1-dependent signaling contributes to CLL cell activation of NF-κB, which in turn causes autocrine IL-6-induced activation of pSTAT3. As such, this study demonstrates that cirmtuzumab can inhibit leukemia cell activation of both NF-κB and STAT3 in patients with CLL.

Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma.

Cirmtuzumab may enhance the therapeutic activity of ibrutinib by inhibiting ROR1-dependent signaling pathway in patients with chronic lymphocytic leukemia (CLL). Mantle cell lymphoma (MCL) is B-cell malignancy that also expresses ROR1. In this study, we found that the plasma of patients with MCL had high levels of Wnt5a, a ROR1 ligand, that were comparable to those found in patients with CLL; in contrast Wnt5a was virtually undetectable in the plasma of age-matched healthy adults. We also found that Wnt5a induced Rac1 activation in the primary MCL cells. Cirmtuzumab, but not ibrutinib, could inhibit the capacity of Wnt5a to induce primary MCL cells to activate Rac1. Addition of exogenous Wnt5a in vitro significantly enhanced the numbers of MCL cell divisions and the proportion of dividing MCL cells entering S/G2 in MCL cells over time in the presence of CD154 and IL-4/10. Treatment of the MCL cells with cirmtuzumab, but not ibrutinib, blocked Wnt5a-enhanced proliferation of MCL cells. This study indicates that cirmtuzumab and ibrutinib may have complementary activity in the treatment of patients with MCL.

Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia.

Cirmtuzumab is a humanized monoclonal antibody (mAb) that targets ROR1, an oncoembryonic orphan receptor for Wnt5a found on cancer stem cells (CSCs). Aberrant expression of ROR1 is seen in many malignancies and has been linked to Rho-GTPase activation and cancer stem cell self-renewal. For patients with chronic lymphocytic leukemia (CLL), self-renewing, neoplastic B cells express ROR1 in 95% of cases. High-level leukemia cell expression of ROR1 is associated with an unfavorable prognosis. We conducted a phase 1 study involving 26 patients with progressive, relapsed, or refractory CLL. Patients received four biweekly infusions, with doses ranging from 0.015 to 20 mg/kg. Cirmtuzumab had a long plasma half-life and did not have dose-limiting toxicity. Inhibition of ROR1 signaling was observed, including decreased activation of RhoA and HS1. Transcriptome analyses showed that therapy inhibited CLL stemness gene expression signatures in vivo. Cirmtuzumab is safe and effective at inhibiting tumor cell ROR1 signaling in patients with CLL.

Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic protein expressed on chronic lymphocytic leukemia (CLL) that can serve as a receptor for Wnt5a, which can promote leukemia cell migration, proliferation, and survival. We found Wnt5a could induce ROR1 to complex with DOCK2 (dedicator of cytokinesis 2) and induce activation of Rac1/2; these effects could be blocked by cirmtuzumab, a humanized anti-ROR1 monoclonal antibody. We find that silencing DOCK2 specifically impaired the capacity of Wnt5a to induce activation of Rac1/2 or enhance CLL cell proliferation. We generated truncated forms of ROR1 and found the cytoplasmic proline-rich domain (PRD) of ROR1 was required for Wnt5a to induce ROR1 to complex with DOCK2 and activate Rac1/2 in the CLL cell-line MEC1. We introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1-PRD at potential binding sites for the Src-homology 3 domain of DOCK2. In contrast to wild-type ROR1, or other ROR1 P→A variants, ROR1P808A was unable to recruit DOCK2 in response to Wnt5a. Moreover, unlike MEC1 cells transfected with wild-type ROR1 or ROR1 with P→A substitutions at positions 784, 826, or 841, MEC1 cells transfected to express ROR1P808A did not have a growth advantage over MEC1 cells that do not express ROR1. This study reveals that the recruitment of DOCK2 may be critical for the capacity of Wnt5a to enhance CLL proliferation, which may contribute to the observed increased tendency for disease progression in patients who have CLL cells that express high levels of ROR1.

High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia.

ROR1 is an oncoembryonic orphan receptor found on chronic lymphocytic leukemia (CLL) B cells, but not on normal postpartum tissues. ROR1 is a receptor for Wnt5a that may complex with TCL1, a coactivator of AKT that is able to promote development of CLL. We found the CLL cells of a few patients expressed negligible ROR1 (ROR1Neg), but expressed TCL1A at levels comparable to those of samples that expressed ROR1 (ROR1Pos). Transcriptome analyses revealed that ROR1Neg cases generally could be distinguished from those that were ROR1Pos in unsupervised gene-expression clustering analysis. Gene-set enrichment analyses demonstrated that ROR1Neg CLL had lower expression and activation of AKT signaling pathways relative to ROR1Pos CLL, similar to what was noted for leukemia that respectively developed in TCL1 vs ROR1xTCL1 transgenic mice. In contrast to its effect on ROR1Pos CLL, Wnt5a did not enhance the proliferation, chemotaxis, or survival of ROR1Neg CLL. We examined the CLL cells from 1568 patients, which we randomly assigned to a training or validation set of 797 or 771 cases, respectively. Using recursive partitioning, we defined a threshold for ROR1 surface expression that could segregate samples of the training set into ROR1-Hi vs ROR1-Lo subgroups that differed significantly in their median treatment-free survival (TFS). Using this threshold, we found that ROR1-Hi cases had a significantly shorter median TFS and overall survival than ROR1-Lo cases in the validation set. These data demonstrate that expression of ROR1 may promote leukemia-cell activation and survival and enhance disease progression in patients with CLL.

Association of vitamin D receptor gene TaqI, BsmI, FokI and ApaI polymorphisms and susceptibility to extremity chronic osteomyelitis in Chinese population.

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of several inflammatory diseases. However, potential association of the VDR gene polymorphisms with susceptibility to extremity chronic osteomyelitis remains unclear. The present study aimed to investigate link between VDR gene polymorphisms and the risk of extremity chronic osteomyelitis in Chinese population. A total of 233 patients with chronic osteomyelitis and 200 healthy controls were genotyped for the 4 single-nucleotide polymorphisms (SNPs) (TaqI, BsmI, FokI and ApaI) in VDR gene using the SNaPshot genotyping method. The frequencies of mutant allele C in rs731236 (P=0.044, OR=1.830, 95% CI 1.009 - 3.319) and rs2228570 (P=0.029, OR=1.347, 95% CI 1.031 - 1.761) were significantly higher in patients than those in healthy controls. In addition, outcomes of the logistic regression analysis adjusted by gender and age revealed that significant links were found between rs731236 (P=0.05, OR=1.887, 95% CI 1.001 - 3.558), rs2228570 (P=0.042, OR=1.594, 95% CI 1.016-2.500) and the risk of developing chronic osteomyelitis by dominant genetic model. In addition, significant association was also found between rs2228570 and the risk of developing the disease by homozygous model (P=0.034, OR=1.803, 95% CI 1.046 - 3.106). However, no significant correlations were found between BsmI (rs1544410) or ApaI (rs7975232) gene polymorphisms and the susceptibility to the disease. To our knowledge, we reported for the first time that VDR gene TaqI (rs731236) and FokI (rs2228570) polymorphisms may contribute to the increased risk of chronic osteomyelitis in Chinese population.