[Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia].

OBJECTIVE: To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia (CLL). METHODS: The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively. RESULTS: The median age of 59 CLL patients was 60.5(36-78). After one year of BTKi treatment, the CLL clones (CD5 +/CD19 +) of 51 cases (86.4%) were significantly reduced, in which the number of cloned-B cells decreased significantly from (46±6.1)×109/L to (2.3±0.4)×109/L (P =0.0013). But there was no significant change in the number of non-cloned B cells (CD19 + minus CD5 +/CD19 +). After BTKi treatment, IgA increased significantly from (0.75±0.09)g/L to (1.31±0.1)g/L (P <0.001), while IgG and IgM decreased from (8.1±0.2)g/L and (0.52±0.6)g/L to (7.1±0.1)g/L and (0.47±0.1)g/L, respectively (P <0.001, P =0.002). BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients, which manifested as both a decrease in total number of T cells from (2.1±0.1)×109/L to (1.6±0.4)×109/L and NK/T cells from (0.11±0.1)×109/L to (0.07±0.01)×109/L (P =0.042, P =0.038), both an increase in number of CD4 + cells from (0.15±6.1)×109/L to (0.19±0.4)×109/L and CD8 + cells from (0.27±0.01)×109/L to (0.41±0.08)×109/L (both P <0.001). BTKi treatment also up-regulated the expression of interleukin (IL)-2 while down-regulated IL-4 and interferon (IFN)-γ. However, the expression of IL-6, IL-10, and tumor necrosis factor (TNF)-α did not change significantly. BTKi treatment could also restored the diversity of TCR and BCR in CLL patients, especially obviously in those patients with complete remission (CR) than those with partial remission (PR). Before and after BTKi treatment, Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001 (P <0.001), while in patients with PR was 0.01±0.03 and 0.05±0.02 (P >0.05), respectively. Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15 (P <0.001), while in patients with PR was 0.15±0.009 and 0.23±0.18 (P <0.05), respectively. CONCLUSIONS: BTKi treatment can shrink the clone size in CLL patients, promote the expression of IgA, increase the number of functional T cells, and regulate the secretion of cytokines such as IL-2, IL-4, and IFN-γ. BTKi also promote the recovery of diversity of TCR and BCR. BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Efficient biosynthesis of Vibegron intermediate using a novel carbonyl reductase based on molecular modification of hydrogen bonding network regulation.

Vibegron is a novel, potent, highly selective ß3-adrenergic receptor agonist for the treatment of overactive bladder with higher therapeutic capacity and lower side effects. Methyl(2S,3R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-phenylpropanoate ((2S,3R)-aminohydroxy ester) is a key chiral intermediate for the synthesis of Vibegron. A novel carbonyl reductase from Exiguobacterium sp. s126 (EaSDR6) was isolated using data mining technology from GenBank database with preferable catalytic activity. Hydrogen bond network regulation was performed using site-directed saturation mutagenesis and combination mutagenesis. The mutant EaSDR6A138L/S193A was obtained with the activity improvement by 4.58 folds compared with the wild type EaSDR6. The Km of EaSDR6A138L/S193A was decreased from 1.57 mM to 0.67 mM, kcat was increased by 2.17 folds, and the overall catalytic efficiency kcat/Km was increased by 5.07 folds. The organic-aqueous biphasic bioreaction system for the asymmetric synthesis of (2S,3R)-aminohydroxy ester was constructed for the first time. Under the substrate concentration of 150 g/L, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99%, and the spatiotemporal yield was 1.55 g/(L·h·g DCW) after 12 h reaction. While the substrate concentration was increased to 200 g/L and the reaction lasted for 36 h, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99% and the spatiotemporal yield was 1.05 g/(L·h·g DCW). The substrate concentration and spatiotemporal yield were higher than ever reported.

Circular RNA PVT1 Regulates Cell Proliferation, Migration, and Apoptosis by Stabilizing c-Myc and Downstream Target CXCR4 Expression in Acute Myeloid Leukemia

Objective: This study aimed to investigate the role and mechanism of circular RNA PVT1 (circPVT1) in patients with acute myeloid leukemia (AML). Materials and Methods: The expression of circPVT1 in 23 patients with de novo AML (not acute promyelocytic leukemia, not APL) and cell lines were detected by RT-qPCR. Loss of function assays were carried out to explore the influence of silenced circPVT1 on the proliferation, migration, and apoptosis in the THP-1 cell line. CCK-8 assays, trans-well assays, and annexin V/PI staining assays were performed to assess proliferation, migration, and apoptosis, respectively. Results: CircPVT1 was highly expressed in AML patients and myeloid cell lines compared to healthy controls. Higher expression of circPVT1 was related to shorter overall survival (OS) and relapse-free survival (RFS) in AML patients. Cell viability and migration were inhibited and apoptosis was increased when circPVT1 was knocked down in THP-1 cells. Knockdown of circPVT1 resulted in marked suppression of c-Myc protein with no significant change in mRNA levels. We also found that circPVT1 knockdown markedly increased the phosphorylation of c-Myc Thr-58, which was responsible for c-Myc degradation. Silencing of c-Myc caused a significant decrease in CXCR4 mRNA and protein expression, whereas the overexpression of c-Myc caused the opposite result, suggesting that CXCR4 is a target molecule of c-Myc. Finally, we found that overexpression of c-Myc could partially reverse circPVT1 knockdown-induced anti-tumor effects on THP-1 cells in vitro. Conclusion: Our findings showed that circPVT1 was highly expressed in AML patients and was related to shorter OS and RFS. CircPVT1 may exert an oncogenic effect in THP-1 cells by stabilizing c-Myc protein expression and downstream target CXCR4 expression. These data indicate that circPVT1 may be a promising therapeutic target for AML.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine.

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Necroptosis-associated long noncoding RNAs can predict prognosis and differentiate between cold and hot tumors in ovarian cancer.

Objective: The mortality rate of ovarian cancer (OC) is the highest among all gynecologic cancers. To predict the prognosis and the efficacy of immunotherapy, we identified new biomarkers. Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) databases were used to extract ovarian cancer transcriptomes. By performing the co-expression analysis, we identified necroptosis-associated long noncoding RNAs (lncRNAs). We used the least absolute shrinkage and selection operator (LASSO) to build the risk model. The qRT-PCR assay was conducted to confirm the differential expression of lncRNAs in the ovarian cancer cell line SK-OV-3. Gene Set Enrichment Analysis, Kaplan-Meier analysis, and the nomogram were used to determine the lncRNAs model. Additionally, the risk model was estimated to evaluate the efficacy of immunotherapy and chemotherapy. We classified necroptosis-associated IncRNAs into two clusters to distinguish between cold and hot tumors. Results: The model was constructed using six necroptosis-associated lncRNAs. The calibration plots from the model showed good consistency with the prognostic predictions. The overall survival of one, three, and five-year areas under the ROC curve (AUC) was 0.691, 0.678, and 0.691, respectively. There were significant differences in the IC50 between the risk groups, which could serve as a guide to systemic treatment. The results of the qRT-PCR assay showed that AL928654.1, AL133371.2, AC007991.4, and LINC00996 were significantly higher in the SK-OV-3 cell line than in the Iose-80 cell line (P < 0.05). The clusters could be applied to differentiate between cold and hot tumors more accurately and assist in accurate mediation. Cluster 2 was more vulnerable to immunotherapies and was identified as the hot tumor. Conclusion: Necroptosis-associated lncRNAs are reliable predictors of prognosis and can provide a treatment strategy by screening for hot tumors.

Growth dynamics and tissue localization of a Coxiella-like endosymbiont in the tick Haemaphysalis longicornis.

A Coxiella-like endosymbiont (Coxiella-LE hereinafter) stably infects and influences Haemaphysalis longicornis development, indicating a mutualistic relationship of Coxiella-LE and ticks. To further elucidate the patterns of growth dynamics and tissue localization of Coxiella-LE in H. longicornis, 16S rRNA high-throughput sequencing, quantitative PCR (qPCR), and fluorescence in situ hybridization (FISH) were used in this study. The density of Coxiella-LE varied among different tick life stages, and fed female ticks had the highest density, followed by unfed female and unfed larval ticks. In the four organs that were dissected from fed female ticks, the ovary carried the highest density of Coxiella-LE, which was significantly different from salivary glands, midgut and Malpighian tubules. The high abundance of Coxiella-LE in fed female ticks and in the ovaries of fed female ticks in the bacterial microbiota analyses further confirmed that Coxiella-LE rapidly proliferates in the ovary after blood feeding. The ovaries continued to develop after engorgement and oviposition began on day 5, with a significant decrease in the density of Coxiella-LE in the ovaries occurring on day 7. FISH results indicated that Coxiella-LE is mainly colonized in the cytoplasm of the oocyte and proliferates with oogenesis. Coxiella-LE was expelled from the body with the mature oocyte, ensuring its vertical transmission. In the Malpighian tubules at different days after engorgement, the white flocculent materials were increasing, and the density of Coxiella-LE raised significantly on day 7. Unlike the localization pattern in the ovary, Coxiella-LE was initially distributed in a mass and continually increased during the development of Malpighian tubules until it filled the Malpighian tubules. These findings provide new insights on the growth dynamics and tissue localization of Coxiella-LE in ticks and are useful for further investigation on the interactions of symbiont and ticks .

Bacterial microbiota analysis demonstrates that ticks can acquire bacteria from habitat and host blood meal.

Ticks have a diversity of habitats and host blood meals. Whether and how factors such as tick developmental stages, habitats and host blood meals affect tick bacterial microbiota is poorly elucidated. In the present study, we investigated the bacterial microbiotas of the hard tick Haemaphysalis longicornis, their blood meals and habitats using 16S rRNA gene high-throughput sequencing. The bacterial richness and diversity in ticks varied depending on the tick developmental stage and feeding status. Results showed that fed ticks present a higher bacterial richness suggesting that ticks may acquire bacteria from blood meals. The significant overlap of the bacteria of fed ticks and the host blood also supports this possibility. Another possibility is that blood meals can stimulate the proliferation of certain bacteria. However, most shared bacteria cannot transmit throughout the tick life cycle, as they were not present in tick eggs. The most shared bacteria between ticks and habitats are members of the genera Staphylococcus, Pseudomonas, Enterobacter, Acinetobacter and Stenotrophomonas, suggesting that these environmental bacteria cannot be completely washed away and can be acquired by ticks. The predominant proportion of Coxiella in fed females further demonstrates that this genus is involved in H. longicornis physiology, such as feeding activity and nutritional provision. These findings further reveal that the bacterial composition of ticks is influenced by a variety of factors and will help in subsequent studies of the function of these bacteria.

Elucidating the interaction of rhizosphere bacteria and environmental factors in influencing active ingredient content of Lycium barbarum fruit in China.

AIMS: This study aimed to compare the differences in the bacterial community structure of Lycium barbarum rhizosphere and elucidate the contribution of rhizosphere bacteria to the active ingredients of L. barbarum fruit. METHODS AND RESULTS: This study investigated the soil and meteorological characteristics of L. barbarum rhizosphere during three growth stages across three production regions of China. High-throughput sequencing showed significant differences in the bacterial community diversity of L. barbarum rhizosphere across the three production regions, and norank_o_Gaiellales, norank_f_Anaerolineaceae and norank_f_AKYG1722 were the highest in Ningxia. In addition, regression and path analysis revealed that pH, norank_o_Gaiellales and norank_f_AKYG1722 significantly promoted the accumulation of total sugar and flavonoids in L. barbarum fruit directly or indirectly. Soil organic matter (SOM), norank_f_Anaerolineaceae and humidity significantly promoted the accumulation of betaine. The average temperature during the growth stages, norank_f_AKYG1722, and norank_o_Gaiellales promoted the accumulation of polysaccharides. CONCLUSIONS: The interaction between rhizosphere bacteria and environmental factors promoted the accumulation of active ingredients in L. barbarum fruits. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provided insights to improve the quality of L. barbarum fruit.

Effect of aromatherapy on autonomic nervous system regulation with treadmill exercise-induced stress among adolescents.

INTRODUCTION: Stress is a major health issue in adolescents owing to the important transitions experienced during this period. Aromatherapy is an effective method for the reduction of stress in adolescents. PURPOSE: The aims of this study were to examine the effect of aromatherapy on the regulation of the autonomic nervous system (ANS) along with stress relief and to explore the effect of aromatherapy on adolescents with different levels of stress. METHODS: This quasi-experimental study comprised three types of treatments: control (no essential oil), pure essential oil therapy (sandalwood), and blended essential oil therapy (sandalwood-lavender). The heart rate variability (HRV) was calculated to evaluate the post-exercise recovery of the ANS to the baseline level in the recruited adolescents. To examine the efficiency of aromatherapy, Friedman test was used to assess the significance of difference in all parameters (i.e., mean heart rate, SDNN, normalized LF, normalized HF, and LF/HF) between baseline and after exercise among the three treatment conditions. RESULTS: The participants comprised 43 junior college students (8 males and 35 females) with a mean age of 18.21 ± 0.99. Significant differences in changes of two HRV parameters (normalized LF and LF/HF) were associated with both essential oil therapies compared to those in the control group (p<0.05), and one more HRV parameter (normalized HF) exhibited significant difference related to blended essential oil therapy compared to that of the control group. Besides, changes in two HRV parameters (mean heart rate and normalized HF) of both essential oil therapies in the low level stress subgroup showed significant differences compared to those of the control group (p<0.05). CONCLUSIONS: This study demonstrated that aromatherapy could be used for ANS regulation with stress-relieving effects in adolescents. The participants with a low stress level appeared to respond better to the blended essential oil therapy, whereas those with medium to high levels of stress appeared to respond poorly to aromatherapy compared to the control.

Does Interpersonal Interaction Really Improve Emotion, Sleep Quality, and Self-Efficacy among Junior College Students?

This study discusses the correlation between teenagers' real-life interpersonal interactions and teenagers' online interpersonal interactions with regards to emotion, sleep quality, and self-efficacy. This study adopted a cross-sectional design that included a survey using a structured questionnaire which included demographic data, the Chinese version of the Depression Anxiety Stress Scale (DASS-21), the Pittsburgh Sleep Quality Index (PSQI), the General Self-Efficacy Scale (GSE), the Real Interpersonal Interaction Scale (RIIS), and the Internet Interpersonal Interaction Scale (IIIS). This study enlisted 917 teenage students (age = 17.16 ± 1.48 years). The study found that RIIS had significant negative correlations with DASS and PSQI scores and a significant positive correlation with GSE. Namely, the greater the degree of real-life interpersonal interaction, the lower the degree of negative emotion. Likewise, the more satisfactory sleep quality is, the higher self-efficacy is. In addition, IIIS scores demonstrate significantly positive correlations with DASS and PSQI scores. Therefore, the greater the degree of online interpersonal interaction, the greater the levels of negative emotion, and the poorer the sleep quality is. This study showed that online interpersonal interaction may not improve emotions, sleep quality, or self-efficacy among junior college students. However, real-life interpersonal interaction may improve those three parameters.

Knockdown of IQGAP-1 Enhances Tight Junctions and Prevents P. aeruginosa Invasion of Human Corneal Epithelial Cells.

PURPOSE: To determine the role of IQ-domain GTPase-activating protein1 (IQGAP-1) in tight junctions of human corneal epithelial cells (HCECs) and its effect against P. aeruginosa (PAK) invasion. MATERIAL AND METHODS: Primary human corneal epithelial cells (HCECs), immortalized HCECs, and IQGAP-1 RNA knockdown HCECs (siHCECs) were used. Confocal microscopy, transepithelial electrical resistance (TER), trypan blue exclusion assay and gentamicin invasion assay were done. RESULTS: In primary and immortalized HCECs, IQGAP-1 co-localized with zonular occludin-1 (ZO-1) and actin. Enhanced actin and ZO-1 aggregation were seen in siHCECs. IQGAP-1 knockdown significantly increased TER of immortalized HCECs (P < .0001). Cell viability after PAK infection increased for siHCECs for up to 4 h after infection. PAK intracellular invasion was significantly lowered by 50% in siHCECs at 1 h post-infection. CONCLUSION: IQGAP-1 knockdown increased the strength and integrity of tight junctions and may provide an early protective effect against P. aeruginosa invasion.

Relationships between depression, health­related behaviors, and internet addiction in female junior college students.

INTRODUCTION: Depressive emotions can lead to subsequent unhealthy behaviors such as Internet addiction, especially in female adolescents; therefore, studies that examine the relationships among depression, health­related behaviors, and Internet addiction in female adolescents are warranted. PURPOSE: To examine (1) the relationship between depression and health-related behaviors and (2) the relationship between depression and Internet addiction. METHOD: A cross-sectional study design was adopted using a structured questionnaire to measure depression, health-related behaviors, and Internet addiction in female adolescents. The data were collected from students of a junior college in southern Taiwan using convenience sampling to select the participants. The questionnaire was divided into four sections: demographics, the Center for Epidemiologic Studies Depression Scale (CES-D), the Health Promoting Lifestyle Profile (HPLP), and the Internet Addiction Test (IAT). RESULTS: The final sample comprised 503 female junior college students, with the participants mainly aged between 15 to 22 years (mean age = 17.30 years, SD = 1.34). Regarding the HPLP scores, the overall score, nutrition subscale score, and self-actualization subscale score were significantly and negatively associated with the CES-D depression score (p < 0.05-0.01). In other words, depression level was lower in students who exhibited more healthy behaviors, put more emphasis on dietary health, and had higher levels of self-admiration and confidence toward life. Regarding the IAT scores, the overall score and six domain scores were all positively associated (p < 0.01) to the CES-D depression score. In other words, the higher an individual's Internet addiction score was, the higher her depression level was. CONCLUSIONS: The results confirmed the relationship between depression, health-related behaviors, and Internet addiction. The cultivation of health-related behaviors may help in lowering depressive symptoms. Teenagers with depression have higher risks of developing Internet addiction, and such addiction is likely to affect their daily functioning.

The Relationship Between Sleep Quality and Internet Addiction Among Female College Students.

BACKGROUND: Over 40% of Taiwanese College students experience sleep problems that not only impair their quality of life but also contribute to psychosomatic disorders. Of all the factors affecting the sleep quality, internet surfing is among one of the most prevalent. Female college students are more vulnerable to internet-associated sleep disorders than their male counterparts. Therefore, this study aims to investigate (1) the relationship between internet addiction and sleep quality, and (2) whether significant variations in sleep quality exist among students with different degrees of internet use. METHODS: This structured questionnaire-based cross-sectional study enrolled students from a technical institute in southern Taiwan. The questionnaire collected information on the following three aspects: (1) demography, (2) sleep quality with Pittsburgh Sleep Quality Index (PSQI), and (3) severity of internet addiction using a 20-item Internet Addiction Test (IAT). Multiple regression analysis was performed to examine the correlation between PSQI and IAT scores among the participants. Logistic analysis was used to determine the significance of association between PSQI and IAT scores. RESULTS: In total, 503 female students were recruited (mean age 17.05 ± 1.34). After controlling for age, body mass index, smoking and drinking habits, religion, and habitual use of smartphone before sleep, internet addiction was found to be significantly associated with subjective sleep quality, sleep latency, sleep duration, sleep disturbance, use of sleep medication, and daytime dysfunction. Worse quality of sleep as reflected by PSQI was noted in students with moderate and severe degrees of internet addiction compared to those with mild or no internet addiction. Logistic regression analysis of the association between scores on IAT and sleep quality, demonstrated significant correlations between quality of sleep and total IAT scores (odds ratio = 1.05:1.03 ∼ 1.06, p < 0.01). CONCLUSION: The results of this study demonstrated significant negative association between the degree of internet addiction and sleep quality, providing reference for educational institutes to minimize adverse effects associated with internet use and improve students' sleep quality.

Relationship of sleep quality, smartphone dependence, and health-related behaviors in female junior college students.

INTRODUCTION: Smartphone usage has become commonplace and impact on sleep quality among adolescents. Adolescent girls have a greater tendency toward sleep quality problems. However, relationship of sleep quality, smartphone dependence, and health-related behaviors in female junior college students has not been studied. OBJECTIVES: This study had the two goals: to investigate the relationship between female college students' sleep quality, smartphone dependence, and health-related behaviors, and to identify predictors of sleep quality. METHODS: This study employed a cross-sectional research approach to gather 409 subjects at a junior college in southern Taiwan, and used a structured questionnaire to collect data. The questionnaire consisted of four parts: basic demographic data, the Pittsburgh Sleep Quality Index, assessment of smartphone dependence, and the Health Promoting Lifestyle Profile (HPLP). Logistic regression analysis was employed to check for any association between sleep quality and smartphone dependence or HPLP. RESULTS: Sleep quality was significantly associated with degree of smartphone dependence, total HPLP score, and scores on the four HPLP subscales of nutritional behavior, self-actualization, interpersonal support, and stress management behavior. The lower the subjects' degree of smartphone dependence was, the better their sleep quality was. Furthermore, the degree of smartphone dependence and total HPLP score were significant predictors of sleep quality. CONCLUSIONS: Smartphone dependence is associated with poor sleep quality among female college students. Improving health-related behaviors (nutritional behavior, self-actualization, interpersonal support, and stress management behavior) can also promote improvement in sleep quality.

Information Reception and Expectations Among Hospitalized Elderly Patients in Taiwan: A Pilot Study.

BACKGROUND: Communicating with patients, especially geriatric patients, is a challenge for medical professionals. Medical message receiving and expectations among hospitalized elderly patients have not been studied. PURPOSE: The aim of this study was to explore medical message receiving and expectations concerning medical information among hospitalized elderly patients in Taiwan. METHODS: A descriptive study design was used. Convenience sampling was applied, and the research was conducted in a geriatric ward in a medical center in southern Taiwan. Patients were recruited who were 65 years or older and capable of verbal communication. Data were collected using a self-developed semistructured questionnaire. For each participant, data were collected in one regular ward round. The messages of the physician were recorded. During the first and fourth hours after the ward round, the researcher collected the medical messages that were conveyed by the physician in the ward round and that could be repeated by the patients. Open-ended questions were used to collect data about patient expectations of medical messages during the first hour after the ward round. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using content analysis. RESULTS: Thirty patients participated in this study. All of the participants remembered the visit of the physician. Seventeen participants (56.6%), however, could not repeat the messages, and the total message repetition rate was 17.8% at the first hour after the ward round. By the fourth hour, the message repetition rate fell to 8.9%. Furthermore, three participants (10%) reported messages incorrectly. Participants reported the importance and necessity of physicians conveying medical messages. "Desire to know the reasons for discomfort" and "discharge date" were the messages most expected by the participants. CONCLUSIONS: This study suggests that most hospitalized elderly patients cannot repeat medical messages that are conveyed by their physicians. Written materials and the involvement of principal caregivers in the medical informing process may be necessary. Besides, before providing medical information, medical professionals should be cognizant of the key concerns of their patients.

Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain.

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC50 120 nmol·L-1) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.

[Impacts of Bioremediation on Microbial Communities and Different Forms of Nitrogen in Petroleum Contaminated Soil].

A laboratory study was conducted to investigate the impacts of bioremediation on microbial communities and various nitrogen shifts in petroleum contaminated soil by using GC-MS and Illumia MiSeq technique. Results showed the concentrations of alkane reduced from 25987.8 mg·kg-1 to 12788.6 mg·kg-1, and the concentrations of polycyclic aromatic hydrocarbons (PAHs) decreased from 5322.9 mg·kg-1 to 2917.2 mg·kg-1. Illumia MiSeq results showed that soil microbial communities shifted significantly after remediation, and the relative abundance of some phylum of hydrocarbon degraders (Firmicutes, Bacterodetes), and some genus of degraders (Dietzia, Acinetobacter) increased. Besides, the contents of total nitrogen and ammonia nitrogen increased firstly and then decreased during remediation. However, the contents of nitrate nitrogen decreased at the early stage, and then kept stable in the later stage of remediation. It can be concluded that bioremediation effectively promoted petroleum hydrocarbon degradation, and the different fractional hydrocarbon degradation was related to the relative abundance of hydrocarbon degraders and available nitrogen contents.

[Remediation of Petroleum-Contaminated Soil Using a Bioaugmented Compost Technique].

Bioaugmented compost was created by inoculating petroleum-degrading bacteria into mature compost. The petroleum hydrocarbon degradation efficiencies were investigated by applying this enhanced compost to petroleum-contaminated soil under low temperatures. The results showed that the degrading bacteria can be enriched in the mature compost. After 30 d of remediation, the removal efficiency of TPH, alkanes, and PAHs in the soil was 27.0%, 19.6%, and 10.0%, compared to natural attenuation (CK), which was 4.5%, 9.5%, and 2.3%, respectively. In response to remediation, the relative abundance of Proteobacteria and Actinobacteria phyla decreased from 53.4% and 25.9% to 48.9% and 14.1%, respectively, and Bacteroidetes phylum increased from 5.0% to 24.5%. At the genus level, the relative abundance of Acinetobacter and Pseudomonas increased from 0.02% and 3.4% to 15.2% and 4.6%, respectively. The results indicated that the bioaugmented compost may efficiently facilitate and speed up the bioremediation of petroleum-contaminated soil under low-temperature conditions. Soil microbial diversity and structure of microbial communities are sensitive to the remediation.

Human Adenovirus 36 Infection Increased the Risk of Obesity: A Meta-Analysis Update.

Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P < 0.001) with a high heterogeneity (I = 80.1%; P < 0.001) estimated by the random effect model. Subgroup analysis demonstrated that the pooled OR of HAdV-36 infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P < 0.001) in the adults and children, respectively. Compared to the HAdV-36 negative subjects, the SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P < 0.001). The BMI z-score in the children with HAdV-36 infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.

Vitamin D and Graves' disease: a meta-analysis update.

The association between vitamin D levels and Graves' disease is not well studied. This update review aims to further analyze the relationship in order to provide an actual view of estimating the risk. We searched for the publications on vitamin D and Graves' disease in English or Chinese on PubMed, EMBASE, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the vitamin D levels. Pooled odds ratio (OR) and 95% CI were calculated for vitamin D deficiency. We also performed sensitivity analysis and meta-regression. Combining effect sizes from 26 studies for Graves' disease as an outcome found a pooled effect of SMD = -0.77 (95% CI: -1.12, -0.42; p < 0.001) favoring the low vitamin D level by the random effect analysis. The meta-regression found assay method had the definite influence on heterogeneity (p = 0.048). The patients with Graves' disease were more likely to be deficient in vitamin D compared to the controls (OR = 2.24, 95% CI: 1.31, 3.81) with a high heterogeneity (I2 = 84.1%, p < 0.001). We further confirmed that low vitamin D status may increase the risk of Graves' disease.