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Abstract Traditional villages hold a vital place in Chinese vernacular built heritage continuation with their colors being a significant constituent of the built environment. While digital technology has advanced our understanding of built environment, current research pays little attention on how color influences the environment, often overlooking temporal changes and regional differences, especially neglects color protection measures. This study establishes an diachronic image dataset using national traditional villages in Macheng City, Hubei Province. By using of K-Means and CIEDE2000 algorithms, we analyze color characteristics differences among 4 regions in Macheng City in 2022. And, we select five year’ s diachronic image data of Dongyuan Village (2017–2022) to elucidate the color changes mechanisms. The results show that: (1) Elements influenced by the government, construction techniques dissemination, and environmental factors exhibit regional similarity, while the color of wall differs significantly. Specifically, K-Means values for northern and eastern wall elements indicate light brown tones [RGB: (159, 151, 136), (163, 159, 147)], whereas southwestern and central wall elements exhibit distinct colors, including grayish brown [RGB: (132, 127, 119)] and light yellow [RGB: (190, 182, 161)], respectively. (2) Dongyuan Village underwent color corrections in accordance with government policies, resulting in a shift from blue [RGB: (138, 154, 213)] to yellow [RGB: (223, 206, 196)] for the walls and a gradual unification of road colors into light gray [RGB: (239, 238, 243)]. This initiative led to increased consistency with government guidelines, and the color data stabilized with minimal changes in the surrounding environment. This study enhances our comprehension of traditional village color and regional characteristics changes, contributing to effective measures for the preservation of these culturally significant built heritage.

Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignancies. While PD-1 immune checkpoint inhibitors have demonstrated promising therapeutic efficacy in HCC, not all patients exhibit a favorable response to these treatments. Glutamine is a crucial immune cell regulatory factor, and tumor cells exhibit glutamine dependence. In this study, HCC patients were divided into two subtypes (C1 and C2) based on glutamine metabolism-related genes via consensus clustering. The C1 pattern, in contrast to C2, was associated with a lower survival probability among HCC patients. Additionally, the C1 pattern exhibited higher proportions of patients with advanced tumor stages. The activity of C1 in glutamine metabolism and transport is significantly enhanced, while its oxidative phosphorylation activity is reduced. And, C1 was mainly involved in the progression-related pathway of HCC. Furthermore, C1 exhibited high levels of immunosuppressive cells, cytokine-receptor interactions and immune checkpoint genes, suggesting C1 as an immunosuppressive subtype. After stepwise selection based on integrated four machine learning methods, SLC1A5 was finally identified as the pivotal gene that distinguishes the subtypes. The expression of SLC1A5 was significantly positively correlated with immunosuppressive status. SLC1A5 showed the most significant correlation with macrophage infiltration, and this correlation was confirmed through the RNA-seq data of CLCA project and our cohort. Low-SLC1A5-expression samples had better immunogenicity and responsiveness to immunotherapy. As expected, SubMap and survival analysis indicated that individuals with low SLC1A5 expression were more responsive to anti-PD1 therapy. Collectively, this study categorized HCC patients based on glutamine metabolism-related genes and proposed two subclasses with different clinical traits, biological behavior, and immune status. Machine learning was utilized to identify the hub gene SLC1A5 for HCC classification, which also could predict immunotherapy response.

Abstract Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate‐stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug‐eluting bead TACE (DEB‐TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first‐order branch of the bile ducts (B1‐type bile duct invasion; B1‐BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB‐TACE with cTACE in this patient population. Materials and Methods Using data from five tertiary medical centers (January 2017–December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1‐BDI who underwent DEB‐TACE or cTACE after successful biliary drainage. X‐tile software calculated the pre‐TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. Results The study included 108 patients with unresectable HCC (B1‐BDI) who underwent DEB‐TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB‐TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB‐TACE group exhibited fewer post‐procedural increments in the mean albumin‐bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p 99 μmol/L) had poorer OS in both groups (p

The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of “components-targets-pathways” was established using Cytoscape 3.8.2 and assessed with the “network analyzer” plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(β-d-glucopyranosyl)-furost-5-en3β,22α,26-triol3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.

Abstract Background Limited research exists on the laboratory characteristics of coexistent primary biliary cholangitis (PBC) and Sjögren’s syndrome (SS). This study aimed to investigate the laboratory risk factors for the coexistence of PBC in patients with SS. Methods Eighty-two patients with coexistent SS and PBC (median age 52.50 years) and 82 age- and sex-matched SS controls were retrospectively enrolled between July 2015 and July 2021. The clinical and laboratory characteristics of the two groups were compared. Laboratory risk factors for the coexistence of PBC in patients with SS were analyzed using logistic regression analysis. Results Both groups had a similar prevalence of hypertension, diabetes, thyroid disease, and interstitial lung disease. Compared with the SS group, patients in the SS + PBC group had higher levels of liver enzymes, immunoglobulins M (IgM), G2, and G3 (P 1:10000 in the SS + PBC group was 56.1%, higher than that in the SS group (19.5%, P

Early diagnosis of cancer is crucial to improving the long‐term survival rate of patients. However, commonly used tumor markers lack sensitivity and specificity for screening purposes. Herein, 10 diagnostic models for 10 common types of cancer are developed by extreme gradient boosting, incorporating 66 laboratory parameters. The datasets consist of a retrospective cohort of 737 503 training and 184 012 validation cases, and a prospective cohort of 174 894 cases for model testing. The areas under the curve of the 10 diagnostic models range from 0.763 to 0.993. Notably, the different models have varying numbers of identical parameters among the 66 test features. Additionally, SHapley Additive exPlanation analysis reveals that 54 nontumor markers contributed significantly to the models. Cosine similarity analysis and clustering analysis demonstrate that some of the 10 cancers share common pathophysiological characteristics. Feature‐based inference graph models are thus performed and infer relationships between nontumor index parameters and cancers with strong correlations. In conclusion, a machine learning‐based pan‐cancer early warning system has been established in this study, which can guide doctors in selecting more accurate testing indicators and assessing the risk of 10 types of cancer with greater precision.

Abstract Aims To investigate the efficacy and safety of lenvatinib and idarubicin‐loaded drug‐eluting beads transarterial chemoembolization (IDADEB‐TACE) in primary advanced hepatocellular carcinoma (HCC). Methods This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB‐TACE as first‐line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score‐matching was used to reduce the influence of confounding factors on the outcomes. Results The study reviewed 118 patients who received lenvatinib plus IDADEB‐TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score‐matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post‐treatment ORR (57.7% vs. 25.6%, p

Abstract Background Although Th17 cells and regulatory T cells play critical roles in autoimmune hepatitis, the balance between them in acute and chronic immune hepatitis is not well‐studied. The objective of this study was to explore the role of Th17/Treg balance in autoimmune hepatitis. Methods Thirty female Wistar rats were randomly divided into the following three groups: acute model (AC), chronic model (CC), and healthy control (HC). Aspartate aminotransferase, alanine aminotransferase, and bilirubin levels were measured. Peripheral blood interleukin (IL)‐17, IL‐6, IL‐10, and transforming growth factor‐β cytokine levels were also assessed. Flow cytometry was used to detect changes in the Th17 cell and Treg cell frequency, and the Th17/Treg ratio was calculated. Results The frequency of Th17 cells and Treg cells were both increased (p

Abstract Sjögren's syndrome (SS) is a common chronic inflammatory autoimmune disease that affects about 0.33–0.77% population in China. The positive for antinuclear antibodies (ANA) is one of the key features of SS, which shows a nuclear fine speckled (AC-4) pattern in an indirect immunofluorescent antibody test (IIFT). About 70% of ANA-positive SS patients have detectable anti-SS-A and/or SS-B antibodies, which indicates that other autoantibodies may present in SS patients. The anti-HMGB1 antibodies in 93 SS patients and 96 healthy controls were investigated with in-house developed ELISA and immunoblotting, and the locations of HMGB1 and fluorescent pattern of anti-HMGB1 antibody were investigated with IIFT. The contribution of anti-HMGB1 antibody in ANA-IF was evaluated with Cas9-induce HMGB1 knockout B16 cells. The anti-HMGB1 antibody level is higher in SS patients (9.96 ± 5.55 RU/ml) than in healthy controls (4.9 ± 1.4 RU/ml). With ROC curve analysis, when taking 8 RU/ml as the cutoff value, the sensitivity, specificity, and the area under the curve were 64.5%, 96.9%, and 0.83, respectively. A total of 18 patients (20.7%) with nuclear fine speckled (AC-4) pattern in ANA-IF test were anti-HMGB1 antibody positive only. With commercial antibody, anti-HMGB1 antibody showed the same nuclear fine speckled (AC-4) pattern. The serum from ANA-IF (+), SS-A (−), and SS-B (−) SS patients showed nuclear fine speckled (AC-4) pattern in wildtype B16 cells, but no fluorescence in HMGB1 knockout B16 cells. Anti-HMGB1 antibody may be one of the characteristic autoantibodies of SS in addition to anti-SS-A and SS-B. The detection of anti-HMGB1 antibody can provide more laboratory evidence for clinical diagnosis of SS.

BackgroundCoronavirus disease 2019 (COVID-19) caused by the Omicron variant occurred in Shanghai, China, but its clinical characteristics and virology have not been comprehensively described.MethodsThis retrospective cohort study included adult inpatients (≥18 years) diagnosed with COVID-19 at Changhai Hospital. Laboratory and clinical data were obtained from electronic medical records to investigate the clinical characteristics of COVID-19 and the variations in the patients’ laboratory indexes were examined.ResultsThe symptoms of COVID-19 caused by the Omicron variant were relatively mild. Upper respiratory tract specimens yielded higher positive detection rates than lower respiratory tract and intestinal specimens. Peak COVID-19 viral load was reached at the time of admission; quantification cycle (Cq) values increased to approximately 35 after 8.54 days. In vivo viral shedding duration correlated with age and disease severity (p

Background: Non-apoptotic programmed cell death, including autophagy, ferroptosis, and pyroptosis, newly discovered in recent years, plays an important role in hepatocellular carcinoma (HCC). So, this study attempted to explore the relationship between non-apoptotic programmed cell death-related genes and the molecular characteristics, tumor microenvironment, and prognosis in HCC patients.Methods: The transcriptomic and clinical data of HCC samples were downloaded from various public datasets, followed by acquiring non-apoptotic programmed cell death-related genes from the database. A gene signature model was then constructed using univariate and multivariate Cox regression analyses and validated in other cohorts as well as our institution sequencing data. Kaplan–Meier survival curves and time-dependent receiver operating characteristic curves were generated to evaluate the model’s predictive capability. Furthermore, the relationships among the gene signature, TP53 mutation, stemness, immune status, and responsiveness of transarterial chemoembolization (TACE) were analyzed.Results: The gene signature model was constructed based on five autophagy-, three ferroptosis-, and two pyroptosis-related differentially expressed genes. The model accurately predicted that patients classified as low risk would have better overall survival than high-risk patients, which was robustly consistent with data from other cohorts as well as our institution sequencing data. The comprehensive results indicated that a high-risk index was correlated with a high TP53 mutation rate, high cancer cell stemness, high infiltration of immunosuppressive cells and low immunophenoscore, and low TACE responsiveness of HCC patients.Conclusion: Collectively, the established non-apoptotic programmed cell death-related gene signature was shown to accurately predict prognosis, associated with the TP53 mutation and liver cancer cell stemness, reflect the tumor immune microenvironment, and predict TACE responsiveness in HCC patients.

Abstract To evaluate the feasibility of serum HMGB1, anti-HMGB1 antibodies, and HMGB1/anti-HMGB1 ratio as a diagnosis indicator of initial clinical classification in patients with fever of unknown origin (FUO). Ninety-four patients with classical FUO and ninety healthy controls were enrolled in this study. The subjects’ clinical data and serum were collected. The serum concentration of HMGB1 was detected by a commercial HMGB1 ELISA kit, while the serum concentration of anti-HMGB1 antibodies were detected by an in-house built anti-HMGB1 antibodies ELISA kit and further confirmed by immunoblotting. According to the hospital diagnosis on discharge, ninety-four FUO patients were divided into four groups, Infectious disease subgroup, autoimmune disease subgroup, malignant tumor subgroup, and undetermined subgroup. The concentrations of HMGB1 in the infectious disease subgroup and autoimmune disease subgroup were higher than those in the malignant tumor subgroup, undetermined subgroup, and healthy control group. The concentration of anti-HMGB1 antibodies in autoimmune disease subtype group was higher than those in other subgroups as well as healthy control group. According to the distribution of HMGB1 and anti-HMGB1 in scatter plots of the patients with FUO, we found that the ratio of serum HMGB1/anti-HMGB1 is an ideal clinical indicator for differential diagnosis of different subtypes of FUO. The best cut-off was 0.75, and the sensitivity, specificity, and AUC were 66.67%, 87.32%, and 0.8, respectively. Correlation analysis showed that serum concentration of HMGB1 was moderately correlated with CRP in infectious diseases subgroup, and the serum concentration of anti-HMGB1 antibodies was strongly correlated with erythrocyte sedimentation rate in autoimmune disease subgroup. Our study had showed that serum HMGB1/anti-HMGB1 antibodies ratio can help clinicians identify FUO subtypes, thereby avoiding many unnecessary examinations and tests, and improving the effectiveness of clinical diagnosis and treatment of FUO.

Abstract Background There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Objectives: The re-engineered Xpert MTB/RIF Ultra (Xpert Ultra) assay was developed due to the poor sensitivity of the Xpert MTB/RIF assay for the detection of tuberculosis (TB) in some conditions. This new assay has been recommended by the World Health Organization since 2017. A systematic review and meta-analysis was performed to assess the accuracy of Xpert Ultra for the detection of TB and rifampicin (RIF) resistance. Methods: The Medline (via PubMed), Embase (via OvidSP), ISI Web of Science, Cochrane Central Register of Controlled Trials, and Scopus databases were screened for original articles. Summary sensitivity and specificity were calculated with a bivariate mixed-effects model. A Fagan nomogram was used to assess the clinical utility. The sources of heterogeneity were investigated by meta-regression and subgroup analyses. Results: Sixteen studies were identified. The summary diagnostic accuracy of Xpert Ultra for the diagnosis of TB were as follows: sensitivity 87.2% (95% confidence interval (CI) 82.5–90.8%) and specificity 96.5% (95% CI 95.1–97.5%). For the detection of RIF resistance, sensitivity was 95.1% (95% CI 91.6–97.2%) and specificity was 98.9% (95% CI 97.6–99.5%). Meta-regression showed that the category of population, TB prevalence, reference standard, sample state, sample type, and study design attributed to the heterogeneity. Subgroup analyses found good performance of Xpert Ultra in settings with a low TB burden. Conclusions: As a rapid and highly sensitive test for the detection of TB and simultaneous detection of RIF resistance, Xpert Ultra exhibits a viable alternative in sensitivities in both pulmonary TB (PTB) and extrapulmonary TB (EPTB), which was proved to be higher than Xpert in the comparative analysis, and also shows a good performance in the detection of RIF resistance. Additional studies with comparative consistency tests are needed to precisely describe this finding for more forms of EPTB. Keywords: Xpert MTB/RIF Ultra, Mycobacterium tuberculosis, Diagnosis

Since the famous slow–fast dynamical system referred to as the Hodgkin–Huxley model was proposed to describe the threshold behaviors of neuronal axons, the study of various slow–fast dynamical behaviors and their generation mechanisms has remained a popular topic in modern nonlinear science. The primary purpose of this paper is to introduce a novel transition route induced by the comprehensive effect of special rest spike bistability and timescale difference rather than a common bifurcation via a modified Chua’s circuit model with an external low-frequency excitation. In this paper, we attempt to explain the dynamical mechanism behind this novel transition route through quantitative calculations and qualitative analyses of the nonsmooth dynamics on the discontinuity boundary. Our work shows that the whole system responses may tend to be various and complicated when this transition route is triggered, exhibiting rich slow–fast dynamics behaviors even with a very slight change in excitation frequency, which is described well by using Poincaré maps in numerical simulations.

The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in fibrosarcoma remain unknown. Here, we reported that SAPCD2 expression was markedly elevated in fibrosarcoma tissues, and its expression was differentially upregulated in fibrosarcoma cell lines compared with that in several primary fibroblast cell lines. Kaplan-Meier survival analysis revealed that SAPCD2 overexpression was significantly correlated with early progression and metastasis, and poor prognosis in fibrosarcoma patients. Our results further showed that silencing SAPCD2 inhibited the proliferation and increased the apoptosis of fibrosarcoma cells in vitro. Importantly, silencing SAPCD2 repressed lung metastasis of fibrosarcoma cells in vivo. Mechanistic investigation further demonstrated that silencing SAPCD2 inhibited the proliferation and lung metastasis of fibrosarcoma cells by activating the Hippo signaling pathway, as evidenced by the finding that constitutively active YAP1, YAP1-S127A, significantly reversed the inhibitory effect of SAPCD2 downregulation on the colony formation and anchorage-independent growth capabilities of fibrosarcoma cells, as well as the stimulatory effect on the apoptotic ratio of fibrosarcoma cells. In conclusion, SAPCD2 promotes the proliferation and lung metastasis of fibrosarcoma cells by regulating the activity of Hippo signaling, and this mechanism represents a potential therapeutic target for the treatment of lung metastatic fibrosarcoma.

This study aims to compare the effectiveness and complications of transarterial chemoembolization (TACE) combined with sorafenib (S-TACE) and TACE monotherapy in HCC patients with diffuse recurrence (DR). This retrospective study was approved by our hospital ethics committee, and all patients provided informed consent. We retrospectively enrolled 356 DR patients from January 2005 to December 2014, who underwent either S-TACE or TACE monotherapy. Treatment complications, overall survival (OS) and progression-free survival (PFS) were evaluated. Survival curves were constructed using the Kaplan-Meier method and compared using a log-rank test. Our results found a significant difference between S-TACE and TACE monotherapy in the PFS and OS of HCC patients with early diffuse recurrence (EDR) (p=0.011 and 0.049, respectively). Patients with late diffuse recurrence (LDR) who underwent S-TACE had longer OS (median 24.0 vs. 16.0 months; p=0.044) compared with those in the TACE monotherapy group. Subgroup analysis revealed that S-TACE therapy resulted in higher OS of EDR patients with tumors > 5 cm and HBV-DNA >100 (p=0.036 and 0.035, respectively), compared with patients given TACE monotherapy. S-TACE therapy also resulted in better OS in LDR patients with AFP≥400 ng/ml, AFP28 g/L, and a maximum tumor diameter < 5 cm (p=

Abstract The high prevalence of diabetes mellitus (DM) among multidrug resistant tuberculosis (MDR-TB) patients is a serious cause for concern. We conducted a meta-analysis to determine whether DM is an independent risk factor for MDR-TB. Electronic literature searches of the PubMed, Web of Science and EMBASE databases up to July 12, 2016 were conducted. The pooled adjusted odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random effects model with STATA 12.0 software. In total 13 studies, including 9289 individuals with TB, were included in this meta-analysis. Significant association between DM and MDR-TB (OR = 1.71; 95% CI = 1.32, 2.22) was identified. Subgroup analyses showed that: 1) Pooled OR was 1.25 (95% CI: 0.82–1.91) for cross-sectional studies, and was 2.14 (95% CI: 1.51–3.02) for longitudinal studies; 2) The pooled OR was 1.69 (95% CI:1.09–2.62) for primary MDR-TB, 1.94 (95% CI:1.42–2.65) for any MDR-TB, and 0.85 for secondary MDR-TB (95% CI: 0.29–2.54); 3) DM was significantly associated with MDR-TB in both Caucasian (OR = 2.26, 95% CI: 1.66–3.07) and Asian (OR = 1.40, 95% CI: 1.01–1.95) subgroups. No evidence of publication bias was identified. In conclusion, the pooling analysis indicated that DM was an independent risk factor for MDR-TB, especially for primary MDR-TB.

An efficient method for the preparation of β-amino alcohols catalyzed by lipase TL IM from Thermomyces lanuginosus in a continuous-flow reactor was developed. The eco-friendly biocatalyst combined with continuous-flow reaction technology displayed high efficiency in the synthesis of β-amino alcohols. The benign reaction conditions (35 °C) and short residence time (20 min), together with the use of low cost and readily available starting materials, make this synthetic approach a promising alternative to current β-amino alcohol synthesis.

A continuous-flow procedure for the synthesis of β-amino acid esters has been developed via lipase-catalyzed Michael reaction of various aromatic amines with acrylates. Lipase TL IM from Thermomyces lanuginosus was first used to catalyze Michael addition reaction of aromatic amines. Compared with other methods, the salient features of this work include green reaction conditions (methanol as reaction medium), short residence time (30 min), readily available catalyst and a reaction process that is easy to control. This enzymatic synthesis of β-amino acid esters performed in continuous-flow microreactors is an innovation that provides a new strategy for the fast biotransformation of β-amino acid esters.

Taking construction of personnel positioning system of a Mining Group Company as an example, topology of the system was given, installation and notice in debugging of wellhead inspection card system, installation position requirements of underground substation and card readers were introduced in details, key points of ensuring reliable running of the system and accuracy of monitoring personnel information were also introduced in details. The paper has certain reference for how to establish, use, maintain and manage the underground personnel positioning system.

Abstract Background Rapid and effective treatment of cancer-induced bone pain remains a clinical challenge and patients with bone metastasis are more likely to experience severe pain. The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8. Methods Adult female Wistar rats were used for the study. Cancer pain was induced by inoculation of Walker 256 breast carcinosarcoma cells into the tibia. After surgery, mechanical and thermal hyperalgesia and ambulation scores were evaluated to identify pain-related behavior. We used real-time RT-PCR to determine Nav1.8 mRNA expression in bilateral L4/L5 dorsal root ganglia (DRG) at 16-19 days after surgery. Western blotting and immunofluorescence were used to compare the expression and distribution of Nav1.8 in L4/L5 DRG between tumor-bearing and sham rats. Antisense oligodeoxynucleotides (ODNs) against Nav1.8 were administered intrathecally at 14-16 days after surgery to knock down Nav1.8 protein expression and changes in pain-related behavior were observed. Results Tumor-bearing rats exhibited mechanical hyperalgesia and ambulatory-evoked pain from day 7 after inoculation of Walker 256 cells. In the advanced stage of cancer pain (days 16-19 after surgery), normalized Nav1.8 mRNA levels assessed by real-time RT-PCR were significantly lower in ipsilateral L4/L5 DRG of tumor-bearing rats compared with the sham group. Western-blot showed that the total expression of Nav1.8 protein significantly decreased bilaterally in DRG of tumor-bearing rats. Furthermore, as revealed by immunofluorescence, only the expression of Nav1.8 protein in small neurons down regulated significantly in bilateral DRG of cancer pain rats. After administration of antisense ODNs against Nav1.8, Nav1.8 protein expression decreased significantly and tumor-bearing rats showed alleviated mechanical hyperalgesia and ambulatory-evoked pain. Conclusions These findings suggest that Nav1.8 plays a role in the development and maintenance of bone cancer pain.