A pan-cancer analysis of the MAPK family gene and their association with prognosis, tumor microenvironment, and therapeutic targets.

The mitogen-activated protein kinases family of genes plays a crucial role in a wide range of inflammatory responses in the human body. The MAPK family of genes includes ERK, ERK5, JNK, P-38 mitogen-activated protein kinases. However, the correlation between MAPK family gene expression and pan-cancer prognosis, as well as the tumor microenvironment, has not been extensively studied. This study integrated multiple bioinformatics analysis methods to assess the expression and prognostic value of MAPK family genes, as well as their relationship with tumor microenvironment in patients with pan-cancer. The results showed that ERK, JNK, and P-38 MAPK expression were found to be significantly upregulated in rectum adenocarcinoma (READ), colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma (COADREAD), and kidney renal clear cell carcinoma (KIRC), and significantly downregulated in acute myeloid leukemia. And the results revealed good prognostic results for ERK, JNK, and P-38 MAPK in READ, COADREAD, and KIRC. We observed significant positive correlation between MAPK family gene expression and immune scores especially dendritic cells in READ, COADREAD, and KIRC. And we observed that the expression levels of MAPK family genes were significantly correlated with the expression of immune-related genes, such as CXCL1, CXCL2, CXCL8, CXCR1, CXCR2, CTLA-4, CD80, CD86, and CD28, suggesting their important role in regulating immune infiltrates and tumor progression. Therefore, our study suggested that MAPK family gene plays an important role in regulating immune infiltrates and tumor progression.

[Tongdu Xingshen acupuncture and moxibustion combined with cognitive training in treatment of post-stroke mild cognitive impairment: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of Tongdu Xingshen (promoting the governor vessel and regaining consciousness) acupuncture and moxibustion combined with cognitive training and the simple cognitive training for post-stroke mild cognitive impairment (PSMCI). METHODS: Eighty-four patients with PSMCI were randomly divided into an observation group and a control group, with 42 cases in each group (3 cases in the observation group and 2 cases in the control group dropped off). The observation group was treated by Tongdu Xingshen acupuncture and moxibustion combined with cognitive training, acupuncture was given at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), etc., and moxibustion was given at Shenting (GV 24) , Baihui (GV 20), Shendao (GV 11), Fengfu (GV 16) and Xinshu (BL 15). The control group was only given cognitive training. All the above treatment was given once a day, 5 times a week, for 4 consecutive weeks. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living (ADL) and stroke-specific quality of life (SS-QOL) were compared between the two groups before treatment, after treatment, 4 weeks and 12 weeks after treatment. RESULTS: After treatment, 4 weeks and 12 weeks after treatment, the MoCA, MMSE and SS-QOL scores of the two groups were all higher than those before treatment (P<0.05), and the ADL scores were lower than those before treatment (P<0.05). In the observation group, the MoCA and MMSE scores were higher than those of the control group after treatment, 4 weeks and 12 weeks after treatment (P<0.05), and the SS-QOL score was higher than that of the control group 12 weeks after treatment (P<0.05). CONCLUSION: Both Tongdu Xingshen acupuncture and moxibustion combined with cognitive training and simple cognitive training can improve cognitive function, daily living ability and quality of life in patients with PSMCI, and the combined therapy is superior to simple cognitive training in improving cognitive function and long-term quality of life in patients with PSMCI.

Association of Killer Cell Immunoglobulin-like Receptor and Human Leukocyte antigen-C Genotype with HLA-B27 Associated Acute Anterior Uveitis and Idiopathic Acute Anterior Uveitis in a Chinese Han Population.

PURPOSE: whether killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens C (HLA-C) are associated with HLA-B27 associated acute anterior uveitis (B27AAU) and idiopathic AAU (IAAU) remains unclear. METHODS: PCR with sequence-specific primers was used to analyze KIR genes and HLA-C alleles in a Chinese Han population of 196AAU patients and 210 control subjects. RESULTS: The higher frequencies of HLA-C2 and KIR2DL1/HLA-C2 (p = .009 and p = .044, respectively) and the lower frequencies of HLA-C1C1 and HLA-C1 (p = .034 and p = .009, respectively) were observed in B27AAU than control group. The higher frequencies of KIR2DL2 and KIR2DL2/HLA-C1 (p = .009 and p = .044, respectively) and the lower frequencies of KIR2DL3 and KIR2DL3/HLA-C1 (p = .000 and p = .001, respectively) were observed in IAAU than control group. CONCLUSIONS: HLA-C2 and KIR2DL1/HLA-C2, KIR2DL2, and KIR2DL2/HLA-C1 might be susceptible for B27AAU and IAAU, respectively. HLA-C1C1 and HLA-C1, KIR2DL3 and KIR2DL3/HLA-C1 might protect from B27AAU and IAAU, respectively.

Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis.

Background: Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally. Methods: We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed. Results: We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5-4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively. Conclusions: The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.

Association of Killer Cell Immunoglobulin-like Receptor Genotypes and Haplotypes in Dry Eye Disease Patients Treated with Restasis and Systane.

Purpose: whether the Killer immunoglobulin-like receptor (KIR) genotypes and haplotypes are associated with the improvement in dry eye disease (DED) patients treated with Restasis and Systane (RS) remain unclear.Methods: Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to analyze KIR genes in a Chinese Han population of 198 severe DED patients treated with RS.Results: The higher frequencies of KIR genotype M, AF, AJ and haplotype 2 and 8 (P = .001, P = .03, P = .004, P = .000 and P = .023, respectively) and the lower frequencies of genotype AG and haplotype 1 (P = .000 and P = .000, respectively) were observed in complete responders (CR) than those in null or partial responders (NPR) of DED patients treated by RS.Conclusions: The patients with KIR genotype M, AF and AJ might be of advantage to therapy with RS, which are useful for improving novel personalized precise therapy strategy in DED patients.

Impacts of transportation and meteorological factors on the transmission of COVID-19.

The ongoing pandemic of 2019 novel coronavirus disease (COVID-19) is challenging global public health response system. We aim to identify the risk factors for the transmission of COVID-19 using data on mainland China. We estimated attack rate (AR) at county level. Logistic regression was used to explore the role of transportation in the nationwide spread. Generalized additive model and stratified linear mixed-effects model were developed to identify the effects of multiple meteorological factors on local transmission. The ARs in affected counties ranged from 0.6 to 9750.4 per million persons, with a median of 8.8. The counties being intersected by railways, freeways, national highways or having airports had significantly higher risk for COVID-19 with adjusted odds ratios (ORs) of 1.40 (p = 0.001), 2.07 (p < 0.001), 1.31 (p = 0.04), and 1.70 (p < 0.001), respectively. The higher AR of COVID-19 was significantly associated with lower average temperature, moderate cumulative precipitation and higher wind speed. Significant pairwise interactions were found among above three meteorological factors with higher risk of COVID-19 under low temperature and moderate precipitation. Warm areas can also be in higher risk of the disease with the increasing wind speed. In conclusion, transportation and meteorological factors may play important roles in the transmission of COVID-19 in mainland China, and could be integrated in consideration by public health alarm systems to better prevent the disease.

Epidemiological characteristics of pulmonary tuberculosis among children in Shandong, China, 2005-2017.

BACKGROUND: Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. METHODS: We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005-2017. Data were collected from the China Information System for Disease Control and Prevention. RESULTS: Among 6283 (2.4% of all PTB) PTB cases aged < 18 years, 56.5% were male patients, 39.3% were smear-positive and 98.6% were new cases. The overall incidence of childhood PTB declined (7.62 to 3.74 per 100,000) during 2005-2017, with a non-significant change of annual percentage after 2010. While the incidence of smear-positive PTB (6.09 to 0.38 per 100,000 population) decreased significantly, but the incidence of smear-negative PTB (1.52 to 3.36 per 100,000 population) increased significantly during 2005-2017. The overall treatment success occurred among 94.2% childhood PTB. Ten children (0.2%) died. CONCLUSION: The overall incidence of childhood PTB declined significantly with the disease burden shifting from smear-positive PTB to smear-negative PTB. The discrepancies between notifications and estimations in both TB morbidity and mortality of children need to be addressed urgently.

Epidemiological characteristics of pulmonary tuberculosis in Shandong, China, 2005-2017: A retrospective study.

This study aimed to analyze the epidemiology of pulmonary tuberculosis (PTB) and gained insight into the future TB control plan in China.We extracted epidemiological, clinical, and geographic data from TB prevention and control institutions in 6 cities of Shandong province, China, during 2005 to 2017.Among 224,480 diagnosed PTB, rural residents accounted for 93%, smear-positive PTB 52%, and new cases 92%. The incidence rate of overall PTB declined from 40.8 to 26.25 per 100,000 during 2005 to 2017. Except smear-negative PTB (7.57-19.87 per 100,000), the incidence of smear-positive PTB and all that stratified by age, sex, and treatment history decreased. With 80% reduction, the incidence of smear-positive PTB (6.38 per 100,000) and relapse cases (1.01 per 100,000) were already very low in 2017.With persistent efforts to combat TB, the disease burden had shifted from smear-positive PTB to smear-negative PTB. While new cases need continuous attention, further reducing the incidence of smear-negative PTB and elderly patients may have a greater impact on future TB control.

Oncoprotein HBXIP induces PKM2 via transcription factor E2F1 to promote cell proliferation in ER-positive breast cancer.

We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKM gene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expression at mRNA and protein levels in a dose-dependent manner, as well as increasing the activity of PKM promoter. Mechanistically, HBXIP could stimulate PKM promoter through binding to the -779/-579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP induces PKM2 through transcription factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression.

Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism.

Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl2-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.

Effects of Paclitaxel-conjugated N-Succinyl-Hydroxyethyl Chitosan Film for Proliferative Cholangitis in Rabbit Biliary Stricture Model.

BACKGROUND: Paclitaxel (PTX) could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film (N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]) and evaluated its safety and efficiency using in vivo and in vitro experiments. METHODS:: The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR) measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups (n = 8 in each group): the sham-operated rabbits were used as control (Group A), Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 µmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and α-smooth muscle actin (SMA) immunohistochemical staining of common bile duct were examined. RESULTS:: NMR and FT-IR indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks (8.89 ± 0.03 µg at day 30). The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX (111.7 ± 4.0% vs. 68.1 ± 6.0%, P < 0.001), whereas no statistically significant difference was observed among the three sets of PTX-contained films (67.7 ± 5.4%, 67.2 ± 3.4%, and 59.1 ± 6.0%, P > 0.05). Histological examinations revealed that after 28 days of implantment, Groups D and E (but not Group C) had less granulation tissue and glandular hyperplasia in the site of biliary duct injury than Group B. The pattern was more obvious in Group D than Group E. Less α-SMA-positive cells were found in tissue from Groups D and E. Comparing with Group E, the liver function was improved significantly in Group D, including total bilirubin (2.69 ± 1.03 µmol/L vs. 0.81 ± 0.54 µmol/L, P = 0.014), alanine aminotransferase (87.13 ± 17.51 U/L vs. 42.12 ± 15.76 U/L, P = 0.012), and alkaline phosphatase (60.61 ± 12.31 U/L vs. 40.59 ± 8.78 U/L, P < 0.001). CONCLUSIONS: PTX-SHEC film effectively inhibites the myofibroblast proliferation and extracellular matrix over-deposition during the healing process of biliary reconstruction. This original film might offer a new way for reducing the occurrence of the benign biliary stricture.

Li+-Permeable Film on Lithium Anode for Lithium Sulfur Battery.

Lithium-sulfur (Li-S) battery is an important candidate for next-generation energy storage. However, the reaction between polysulfide and lithium (Li) anode brings poor cycling stability, low Coulombic efficiency, and Li corrosion. Herein, we report a Li protection technology. Li metal was treated in crown ether containing electrolyte, and thus, treated Li was further used as the anode in Li-S cell. Due to the coordination between Li+ and crown ether, a Li+-permeable film can be formed on Li, and the film is proved to be able to block the detrimental reaction between Li anode and polysulfide. By using the Li anode pretreated in 2 wt % B15C5-containing electrolyte, Li-S cell exhibits significantly improved cycling stability, such as∼900 mAh g-1 after 100 cycles, and high Coulombic efficiency of>93%. In addition, such effect is also notable when high S loading condition is applied.

[Effect of Recycled Water Irrieation on Heavy Metal Pollution in Irrigation Soil].

With acceleration of urbanization, water shortages will become a serious problem. Usage of reclaimed water for flushing and watering of the green areas will be common in the future. To study the heavy metal contamination of soils after green area irrigation using recycled wastewater from special industries, we selected sewage and laboratory wastewater as water source for integrated oxidation ditch treatment, and the effluent was used as irrigation water of the green area. The irrigation units included broad-leaved forest, bush and lawn. Six samples sites were selected, and 0-20 cm soil of them were collected. Analysis of the heavy metals including Cr, Mn, Ni, Cu, Zn, As, Cd and Pb in the soil showed no significant differences with heavy metals concentration in soil irrigated with tap water. The heavy metals in the soil irrigated with recycled water were mainly enriched in the surface layer, among which the contents of Cr, Ni, Cu, Zn and Pb were below the soil background values of Beijing. A slight pollution of As and Cd was found in the soil irrigated by recycled water, which needs to be noticed.

Association between Multidrug-Resistant Tuberculosis and Risk Factors in China: Applying Partial Least Squares Path Modeling.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) resulting from various factors has raised serious public health concerns worldwide. Identifying the ecological risk factors associated with MDR-TB is critical to its prevention and control. This study aimed to explore the association between the development of MDR-TB and the risk factors at the group-level (ecological risk factors) in China. METHODS: Data on MDR-TB in 120 counties were obtained from the National Tuberculosis Information Management System, and data on risk-factor variables were extracted from the Health Statistical Yearbook, provincial databases, and the meteorological bureau of each province (municipality). Partial Least Square Path Modeling was used to detect the associations. RESULTS: The median proportion of MDR-TB in new TB cases was 3.96% (range, 0-39.39%). Six latent factors were extracted from the ecological risk factors, which explained 27.60% of the total variance overall in the prevalence of MDR-TB. Based on the results of PLS-PM, TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors were all associated with the risk of MDR-TB, but socioeconomic factors were not significant. CONCLUSIONS: The development of MDR-TB was influenced by TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors. Such information may help us to establish appropriate public health intervention strategies to prevent and control MDR-TB and yield benefits to the entire public health system in China.

[Estrogen Receptor Subtype-mediated Luciferase Reporter Gene Assays for Determining (anti) Estrogen Effect of Chemicals].

OBJECTIVE: To establish gene assays for determining (anti) estrogen effect of environmental chemicals; and to compare the reactivity and sensitivity of two assays with different estrogen subtype. METHODS: Human estrogen receptor a (hERalpha) and hERbeta mediated reporter gene assays employing firefly luciferase (Luc) were developed. The expression plasmid hERalpha or hERbeta was constructed and transiently co-transfected into LLC-MK2 cells with pERE-minP-Luc2P reporter plasmid and the control plasmid pGL4.74. Estradiol (E2) and diethylstilbestrol (DES) served as positive test substances to verify the performance of the assays. The effectiveness of the assays for detecting anti-estrogenic activity was tested using 10(-5) mol/L ICI 182, 780 under different concentrations of E2. The performance of the two subtype-mediated assays was verified and compared using bisphenol A (BPA) and genistein (GS). RESULTS: The hERalpha mediated assay found expression of reported gene at 1.9 x 10(-11) mol/L E2; and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 30.7-fold of vehicle control. The hERbeta mediated assay found expression of reporter gene at 2.2 x 10(11) mol/L E2, and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 14.4-fold of vehicle control. ICI 182, 780 inhibited estrogenic activity of E2 significantly. In both assays, E2 failed to induce luciferase activity without hER-pcDNA3.1. BPA and GS induced luciferase activity. CONCLUSION: Both assays have high sensitivity and reproducibility for detecting (anti) estrogen effect. The pGL4-based hERbeta has lower sensitivity than the hERalpha- mediated reporter gene assay. BPA shows stronger estrogenic activity than GS in hERalpha mediated reporter gene assay; whereas, GS shows stronger estrogenic activity than BPA in hERbeta mediated reporter gene assay.

Exploration of ecological factors related to the spatial heterogeneity of tuberculosis prevalence in P. R. China.

BACKGROUND: The current prevalence of tuberculosis (TB) in the People's Republic of China (P. R. China) demonstrates geographical heterogeneities, which show that the TB prevalence in the remote areas of Western China is more serious than that in the coastal plain of Eastern China. Although a lot of ecological studies have been applied in the exploration on the regional difference of disease risks, there is still a paucity of ecological studies on TB prevalence in P. R. China. OBJECTIVE: To understand the underlying factors contributing to the regional inequity of TB burden in P. R. China by using an ecological approach and, thus, aiming to provide a basis to eliminate the TB spatial heterogeneity in the near future. DESIGN: Latent ecological variables were identified by using exploratory factor analysis from data obtained from four sources, i.e. the databases of the National TB Control Programme (2001-2010) in P. R. China, the China Health Statistical Yearbook during 2002-2011, the China Statistical Yearbook during 2002-2011, and the provincial government websites in 2013. Partial least squares path modelling was chosen to construct the structural equation model to evaluate the relationship between TB prevalence and ecological variables. Furthermore, a geographically weighted regression model was used to explore the local spatial heterogeneity in the relationships. RESULTS: The latent ecological variables in terms of 'TB prevalence', 'TB investment', 'TB service', 'health investment', 'health level', 'economic level', 'air quality', 'climatic factor' and 'geographic factor' were identified. With the exception of TB service and health levels, other ecological factors had explicit and significant impacts on TB prevalence to varying degrees. Additionally, each ecological factor had different impacts on TB prevalence in different regions significantly. CONCLUSION: Ecological factors that were found predictive of TB prevalence in P. R. China are essential to take into account in the formulation of locally comprehensive strategies and interventions aiming to tailor the TB control and prevention programme into local settings in each ecozone.