Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Age affects the diagnostic accuracy of the cancer ratio for malignant pleural effusion.

BACKGROUND AND OBJECTIVE: Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. METHODS: The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. RESULTS: Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52-0.68) and 0.63 (95% CI: 0.54-0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. CONCLUSION: Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. KEY MESSAGE: Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Impact of ABCB1 Polymorphisms on Lacosamide Serum Concentrations in Uygur Pediatric Patients With Epilepsy in China.

BACKGROUND: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications. The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric patients with epilepsy. METHODS: The serum concentrations of LCM were determined by ultrahigh performance liquid chromatography, and the ABCB1 polymorphism was analyzed through polymerase chain reaction-fluorescence staining in situ hybridization. The χ2 test and the Fisher exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the one-way analysis of variance and the Mann-Whitney test. RESULTS: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (P < 0.05, OR = 1.966, 95% CI, 1.060-3.647). Patients with the G2677T/A-AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 versus 0.8 ± 0.5 mcg/mL per mg/kg, P < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (P = 0.008 and P = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (P = 0.042). CONCLUSIONS: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.

Diagnostic accuracy of pleural fluid lactate dehydrogenase to adenosine deaminase ratio for tuberculous pleural effusion: an analysis of two cohorts.

BACKGROUND: This study aimed to evaluate the diagnostic accuracy of pleural fluid (PF) lactate dehydrogenase (LDH) to adenosine deaminase (ADA) (LDH/ADA) ratio for tuberculous pleural effusion (TPE). Especially to explore whether the LDH/ADA ratio provides added diagnostic value to ADA. METHODS: The diagnostic accuracy of PF LDH/ADA ratio and ADA for TPE was evaluated in two cohorts, named the BUFF (Biomarkers for patients with Undiagnosed pleural eFFusion) cohort (62 with TPE and 194 with non-TPE) and the SIMPLE (a Study Investigating Markers in PLeural Effusion) cohort (33 with TPE and 177 with non-TPE). Receiver operating characteristic (ROC) curve and decision curve were used to measure the diagnostic accuracy of the PF LDH/ADA ratio. The added diagnostic value of the LDH/ADA ratio to ADA was evaluated with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The area under the ROC curves (AUCs) of PF ADA and LDH/ADA ratio in the BUFF cohort were 0.76 and 0.74, respectively. In the SIMPLE cohort, the AUCs of PF ADA and LDH/ADA ratio were 0.80 and 0.85, respectively. The decision curves of PF LDH/ADA and ADA were close in both the BUFF and SIMPLE cohorts. The NRI and IDI analyses did not reveal any added diagnostic value of LDH/ADA to ADA. CONCLUSIONS: PF LDH/ADA ratio has moderate diagnostic accuracy for TPE. It does not provide added diagnostic value beyond ADA. The current evidence does not support LDH/ADA ratio for diagnosing TPE.

IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors.

BACKGROUND: Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. METHODS: In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells RESULTS: The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. CONCLUSION: Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

Real-world experience with management of spinal ganglioneuroma: long-term follow-up observations of 31 cases.

INTRODUCTION: Spinal ganglioneuroma (GN) is the most benign neoplasm of neuroblastic origin. There is little knowledge about spinal GN because of sporadic cases reported. The objective of this study is to describe the clinical manifestations and long-term follow-up outcomes of spinal GN after consecutive treatment. METHODS: The clinical and follow-up data of 31 patients with spinal GN receiving consecutive treatment in our institute are retrospectively analyzed. RESULTS: The mean age of the 31 patients was 40.39 ± 14.8 years. They were diagnosed with spinal GN and received surgical treatment in our institution between February 2012 and August 2019. Of them, 22 (71%) patients presented preoperative neurological symptoms. The mean duration from symptom onset to surgery was 19.76 ± 49.59 months. Eighteen patients received complete surgical resection and 13 patients received subtotal excision. In addition, radicotomy was performed simultaneously after sophisticated consideration in 19 patients. The follow-up period averaged 64.13 ± 22.67 months. The preoperative neurological dysfunction was improved significantly during the follow-up period in all cases. No local recurrence or malignant transformation has occurred so far. CONCLUSION: Spinal GN is a rare but benign neoplasm, and the origin of spinal GN remains controversial. With our experience, we propose that the origin of spinal GN from dorsal root ganglion should be equally considered as its counterpart of sympathetic ganglion. Complete resection is the preferred surgical strategy to avoid malignant events and recurrence. And the close postoperative follow-up observations are warranted.

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats.

Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1ß, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

Participation in healthcare behavior by adolescents with epilepsy and factors that influence it during the transition period: A cross-sectional study in China.

PURPOSE: Given the importance of adolescents' participation in the care of their chronic diseases during their transitional period in the healthcare system, the present study investigated the degree of participation in healthcare behavior by Chinese adolescents with chronic epilepsy and identified factors that should be addressed by health interventions. METHODS: The study used a convenience sample of 1238 adolescent patients with epilepsy, who were hospitalized in 17 tertiary A-level children or maternal and child specialty hospitals in China between January 2017 and March 2020. Several scales were used to measure their degree of participation in healthcare behavior and the factors that influence it. Data collection was conducted after uniform training of the investigators. The adolescents who met the inclusion and exclusion criteria could scan the QR code of the questionnaire via a mobile phone. RESULTS: The age of the participants ranged from 12.2 to 17.8 years (mean 14.2 years), and the sample had a male-to-female ratio of 1.25:1. The patients' average total score of participation in healthcare behavior was 125.58 (SD = 12.25), which was lower than the norm for China. Their scores on the six dimensions of participation were highest for information interaction, followed in descending order by medical decision-making, treatment and care, appeal, diagnosis and treatment decision-making, and questioning supervision. Multiple linear regression found significant associations between health-care participation and five personal and disease variables (gender, age, course of disease, number of comorbid diseases, type of family structure), self-efficacy, and coping styles (cognitive-palliative and acceptance), which explained 52.1% of the variance in patients' total scores on participating in healthcare behavior. CONCLUSIONS: The participation of young Chinese patients with epilepsy in transitional healthcare behavior needs to be improved. Participation was positively associated with being female, a longer course of disease, fewer comorbidities, and living in a nuclear family. Patients who used cognitive-palliative and acceptance coping styles and those who had higher self-efficacy also had significantly higher levels of participation in healthcare behavior. The study provides useful reference points for adolescents with chronic disease to participate in healthcare programs, in order to achieve a smooth transition from childhood to adulthood.

Routine Intraoperative Inhaled Milrinone and Iloprost Reduces Inotrope Use in Patients Undergoing Cardiac Surgery: A Retrospective Cohort Pilot Study.

BACKGROUND: Catecholamine inotropes are frequently used after cardiopulmonary bypass (CPB) but may have undesirable effects. The aim was to identify whether the routine use of inhaled pulmonary vasodilators might reduce the requirement for inotrope drugs after cardiac surgery. METHODS: Retrospective cohort study of sequential patients undergoing cardiac surgery at the Royal Melbourne Hospital performed by a single surgeon and anesthesia care team, within 14 months before and after routine implementation of inhaled pulmonary vasodilators, August 2017. Milrinone 4 mg and iloprost 20 µg were inhaled using a vibrating mesh nebulizer (Aerogen) before initiation of CPB and at chest closure. Other aspects of clinical management were unaltered over the time period. Two investigators blinded to each other extracted data from electronic and written medical records. The primary outcome was any use of inotropes in the perioperative period; a Fisher exact test was used to analyze any differences between the 2 groups. Demographic data, hemodynamic data, and use of inotropes and vasopressors were collected from induction of anesthesia to 36 hours postoperative in the intensive care unit (ICU). Hospital and ICU length of stay, cost, and complications were collected. RESULTS: Any use of inotropes was significantly lower with inhaled pulmonary dilators (62.5% vs 86.8%, odds ratio [95% confidence interval {CI}], 0.253 (0.083-0.764); P = .011), including intraoperative inotrope use (37.5% vs 86.8%, odds ratio [95% CI], 0.091 (0.03-0.275); P < .001). ICU length of stay was significantly lower with inhaled pulmonary dilators (45 hours, interquartile range [IQR], 27-65 vs 50 hours, IQR, 45-74; P = .026). There were no significant differences among major postoperative complications or costs between groups. CONCLUSIONS: Routine use of inhaled milrinone 4 mg and iloprost 20 µg before and after CPB is associated with reduced postoperative inotrope use.

[Study on anti-osteoporosis effect of Eucommiae Cortex based on GC-MS metabonomics].

Based on GC-MS metabolomics and biochemical index analysis, the mechanism of bone mass loss in osteoporosis and the evaluation of anti-osteoporosis in Eucommiae Cortex were studied. The OVX rats model was established by bilateral ovariectomized. The routine indexes such as BMC, BMD, BGP and TRAP5 b were determined. The GC-MS technique was used to analyze the metabolism profile of serum samples between the control group, model group and medicine group, and multiple statistical analysis methods including principal component analysis(PCA), partial least squares-linear discriminant analysis(PLS-LDA) and subwindow rearrangement analysis(SPA) were used to screen and identify biomarkers. Five metabolites were selected as potential biomarkers, glycine, lysine, tryptophan, docosahexaenoic acid and glucose. Except for the significant increase of tryptophan in serum of OVX rats, the other four metabolites were significantly decreased. Moreover, the five biomarkers of the medicine group had a trend of returning to rats in control group. The significantly altered metabolite levels indicated that Eucommiae Cortex may relieve the symptoms of osteoporosis by regulating amino acid metabolism and oxidative stress.

[Investigation of microbial community involved in fermentation of Massa Medicata Fermentata].

This study aimed to clarify the microbial diversity, dominant species and the change of community structures in the fermentation of Liushenqu(Massa Medicata Fermentata), and explore the material foundation of its pharmacodynamics effect. On the basis of standardizing the fermentation process, Massa Medicata Fermentata was prepared by screening and optimizing the recipes and the standard formula issued by the Ministry. The community structure and growth process of fungi and bacteria in the samples at five time points(0, 17, 41, 48, 65 h) in the fermentation process of Massa Medicata Fermentata were analyzed by using isolation and culture of eight different media and high-throughput DNA sequencing technology. The results indicated that the samples of the two recipes pre-sented high microbial diversity at the initial fermentation stage, with Aspergillus spp. as the dominant species. As the fermentation process goes forward, Saccharomycopsis fibuligera and Rhizopus oryzae soon became dominant species from 17 h after fermentation commencement point to the fermentation end, while the other species were inhibited at a lower level from 17 h. The species diversity of bacteria in the initial fermentation samples was also high, and Enterobacter was the dominant species. Enterobacter cloacae, Pediococcus pentosaceus and Cronobacter sakazakii became dominant bacterial species 17 h after fermentation commencement, while the species diversity was decreased. Our results will be a scientific basis for promoting the fermentation process of Massa Medicata Fermentata by using pure microbial cultures.

[Research progress of effect of anxiolytic traditional Chinese medicines and formulas on neurotransmitters].

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.

International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community.

How to cite this article: Xiao-Bo H, Poonyathawon S, Semedi BP, Xiao-Yi Z, Wei F, Da-Wei W, et al. International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community. Indian J Crit Care Med 2020;24(4):283-284.

[Correlation between the genotypes and clinical symptoms of human papilloma virus in male outpatients at STD clinics].

OBJECTIVE: To investigate the distribution of the human papilloma virus (HPV) and its genotypes in the male outpatients at the clinics of sexually transmitted diseases (STD) in Changshu and analyze its association with the primary clinical symptoms so as to provide some evidence for the prevention and treatment of HPV infection in men. METHODS: We collected exfoliated cell samples from the external genitals of 602 male outpatients at the STD clinics in Changshu from February 2016 to February 2018, extracted and amplified nucleic acids from the samples, and detected the HPV genotypes using the gene chip technique. We performed statistical analyses on the types of symptoms in clinical diagnosis and their correlation with the genotypes of HPV using the chi-square test. RESULTS: The HPV positive rate in the male STD clinics was 48.2%, of which 47.2 % fell into the low-risk type, 30.0% with multiple infections. The main genotypes included HPV types 6, 11, 39, and 52, and the main HPV-related clinical symptoms were verruca (43.1%) and erythra (41.0%). Low-risk types 6 and 11 accounted for a significantly higher percentage than the high-risk types in the verruca patients (60.0% vs 15.0%, , P < 0.05), but showed no statistically significant difference from the latter in the erythra patients (38.7% vs 38.7%, P > 0.05). The incidence of low-risk infection was remarkably higher than that of high-risk infection in the acrobystitis and balanitis patients (P < 0.05), while the high-risk types constituted a markedly higher percentage than the low-risk and high- and low-risk mixed types in the asymptomatic men at physical examination (84.6% vs 0.0% and 15.4%, P < 0.05). CONCLUSIONS: The HPV positive rate was as high as 48.2% in the males at the STD clinics in Changshu, and the main infection type was low-risk genotype single infection. The clinical symptoms of low-risk infection were mainly verruca and prepuce balanitis, and the high-risk type was mostly asymptomatic at physical examination.

Preferential flow characteristics of reclaimed mine soils in a surface coal mine dump.

There are a large number of macropores/tubular channels of a few centimeters and plant roots in reclaimed dump soils, which are the main reasons for the formation of soil macropores and soil preferential flow. To systematically study the morphological characteristics and variation of soil preferential flow for different reclaimed vegetations in a dump, a dye-staining experiment and physical and chemical analysis were carried out to investigate the formation mechanism and influencing factors of soil preferential flow in the vegetation restoration process. The results indicate that there were differences in the soil water breakthrough curves for different plots. The macropore effluent rate generally increased at first and then tended to stabilize. The soil steady effluent rate decreased with increasing soil depth, which reached the maximum and minimum values at the depths of 0∼5 cm (0.0193∼0.0315 mm s-1) and 50∼60 cm (0.0028∼0.0035 mm s-1), respectively. Furthermore, the radius of soil macropores under different types of reclaimed vegetation ranged from 0.03 to 4.71 mm, most of which ranged from 0.11 to 2.36 mm. The soil macroporosity of different reclaimed vegetation types ranged from 0.03 to 16.58%, which was significantly greater than 5%. The soil macroporosity determined 65% of the variation in the steady effluent rate and 42% of the variation in the saturated hydraulic conductivity. Furthermore, the dye coverage ratio decreased as the soil layer depth increased in different plots, and there were some differences in each plot. The maximum dye coverage ratio occurred in the 0∼5 cm soil layer, which reached 90.37%. The dye coverage ratio at a depth of 0∼60 cm in six plots followed the order of Robinia pseudoacacia (26.48%) > Ulmus pumila (20.12%) > mixed forest (17.32%) > farmland (15.06%) > shrub (13.97%) > weeds (10.07%). The soil preferential flow mostly occurred in the 0∼40 cm soil depth layer, which occupied more than 93% of the total soil profile (0∼60 cm). Moreover, a Pearson correlation was used to analyze the relationship between environmental factors (soil, water, and plant factors) and the dye coverage ratio. The dye coverage ratio of soil preferential flow under different reclamation vegetations was very significantly or significantly positively correlated with the gravel content, mean radius of soil macropores, soil saturated hydraulic conductivity, root weight density, and root length density, which promoted the formation and development of soil preferential flow. This study will provide a scientific basis for understanding the formation mechanism and perfecting the research system of soil preferential flow, vegetation restoration, and reconstruction in a dump; furthermore, this research offers significance guidance in the construction of green mines and the development of regional economics.

Activated STING enhances Tregs infiltration in the HPV-related carcinogenesis of tongue squamous cells via the c-jun/CCL22 signal.

The negative role of the activated stimulator of IFN genes (STING) has been uncovered in autoinflammatory disease and cancer. However, the role of STING in virus-related carcinogenesis is not well known. Herein, HPV(+) tongue squamous cell carcinoma (TSCC) (n=25) and HPV(-) TSCC samples (n=25) were randomly collected and were verified by in situ hybridization (ISH) and p16 immunohistochemistry (IHC) to assess the expression and activated status of STING through IHC. The results showed that the expression of STING was up-regulated during the development of TSCC. Interestingly, although the expression of STING showed no difference between HPV(+/-) TSCC samples, the activated status of STING with dark staining around the nucleus was observed in HPV(+) TSCC samples. The role of activated STING was analyzed in three cell lines by siRNA and indicated that activated STING had no impact on cell viability or apoptosis but promoted the induction of several immunosuppressive cytokines, e.g., IL-10, IDO and CCL22, which facilitated the infiltration of regulatory T cells (Tregs). Moreover, increased infiltration of Foxp3(+) Tregs along with increased expression of CCL22 was confirmed in HPV(+) TSCC samples. An inhibitor of the MAPK/AP-1 pathway (U0126) and the silencing of c-jun significantly suppressed CCL22 induction and the recruitment of Tregs by activated STING. Furthermore, down-regulated miR-27 was verified in independent fresh TSCC samples (n=50) and eight cell lines, which enhanced STING activation and led to increased CCL22 expression for Tregs recruitment in the TSCC microenvironment. Therefore, our findings provided distinct insight into the side effects of activated STING in HPV-related carcinogenesis.

Prognostic value of ABO blood group in patients with gastric cancer.

BACKGROUND: Previous studies have shown a link between the ABO blood groups and prognoses for several types of malignancies. However, little is known about the relationship between the ABO blood groups and prognosis in patients with gastric cancer (GC). The aim of this study was to investigate the prognostic performance of ABO blood groups in patients with GC. METHODS: A total of 1412 GC patients who had undergone curative intent surgery between January 2005 and January 2010 participated in the present study. A prognostic nomogram was constructed to improve the predictive capacity for patients with gastrectomy using R software, and its predictive accuracy was determined by the concordance index (c-index). RESULTS: The median follow-up period of the 1412 GC patients was 44 mo with 809 alive. Non-AB blood groups were associated with significantly decreased overall survival in GC patients (hazard ratio = 2.59; 95% confidence interval = 1.74-3.86, P < 0.001), but patients in the group AB had a better prognosis than those in the non-AB blood groups. Meanwhile, group A had the worst prognosis among all the blood groups (hazard ratio = 3.14; 95% confidence interval = 2.09-4.72; P < 0.001). In addition, our constructed nomogram, superior to that of the traditional AJCC stage system (c-index: 0.69), could more accurately predict overall survival (c-index: 0.78) in GC patients who had undergone gastrectomy. CONCLUSIONS: The blood group AB is a favorable prognostic factor for GC patients, but the blood group A is an adverse prognostic factor for patients with gastrectomy. Further prospective studies are warranted to confirm this relationship.

[Transforming growth factor-ß1 induces epithelial-mesenchymal transition in A549 cells by up-regulating expression of calpain].

OBJECTIVE: To investigate the effect of transforming growth factor-ß1 (TGF-ß1) on epithelial-mesenchymal transition in type II alveolar epithelial cells and the relationship with Calpain. METHODS: The type II alveolar epithelial cell line-A549 cells cultured in vitro were divided into 4 groups: the control group, the TGF-ßl group, the TGF-ß1 + PD150606 group, the PD150606 group. Given the corresponding processing,Western-blot and RT-PCR were utilized to evaluate the expression of Calpain- 1,E-cad and α-SMA. RESULTS: Compared with the control group, the protein and mRNA expression of Calpain-1 and α-SMA in the TGF-ß1 group was markedly increased, but the protein and mRNA expression of E-cad was significantly decreased. While, after calpain inhibitor PD150606 was added, the protein and mRNA expression of Calpain-1 and α-SMA was markedly decreased and the protein and mRNA expression of E-cad was significantly increased in the TGF-ßl + PD150606 group, but there was no difference between TGF-ß1 + PD150606 group and control group. But with Calpain inhibitor PD150606 alone, the expression of Calpain-1,E-cad and α-SMA was no difference with the control group. CONCLUSIONS: TGF-ßl could induce epithelial-mesenchymal transition in A549 cells by up-regulating expression of calpain which could be inhibited by calpain inhibitor PD150606.

Discovery of novel glucagon-like peptide 1/cholecystokinin 1 receptor dual agonists.

The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. The potential of developing novel dual agonists targeting both cholecystokinin 1 (CCK-1) receptor and glucagon-like peptide 1 (GLP-1) receptor to improve the treatment of type 2 diabetes and obesity have not been fully explored. In this investigation, we reported a series of novel GLP-1/CCK-1 receptor co-agonists constructed by linking the C-terminus of a GLP-1 receptor agonist (bullfrog GLP-1) to the N-terminus of a CCK-1 receptor selective agonist NN9056. In comprehensive in vitro assays, these co-agonists exhibited complete agonistic potency on GLP-1 and CCK-1 receptor. Remarkably, 1f displayed superior hypoglycemic and insulinotropic effects when compared to NN9056 and semaglutide. Evaluation in Kunming and diet-induced obesity (DIO) mice unveiled significant acute and enduring hypoglycemic effects of 1f. Administration of 1f to DIO mice resulted in substantial weight loss, normalized lipid metabolism, and enhanced glucose regulation. These preclinical observations strongly advocate for the therapeutic potential CCK-1 and GLP-1 pathways could be harnessed in a single fusion peptide, yielding a promising combination therapy strategy for treating metabolic disorders.