Refined moderation analysis with categorical outcomes in precision medicine.

Moderation analysis is an integral part of precision medicine research. Concerning moderation analysis with categorical outcomes, we start with an interesting observation, which shows that heterogeneous treatment effects could be equivalently estimated via a role exchange between the outcome and the treatment variable in logistic regression models. Hence two estimators of moderating effects can be obtained. We then established the joint asymptotic normality for the two estimators, on which basis refined inference can be made for moderation analysis. The improved precision is helpful in addressing the lack-of-power problem that is common in search of moderators. The above-mentioned results hold for both experimental and observational data. We investigate the proposed method by simulation and provide an illustration with data from a randomized trial on wart treatment.

Combating COVID-19 with integrated traditional Chinese and Western medicine in China.

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (Lianhua Qingwen Keli/Jiaonang (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), Jinhua Qinggan Keli (Honeysuckle Flower Cold-Relieving Granules) and Xuebijing (Stasis-Resolving & Toxin-Removing) Injection were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.

The human gastrointestinal microbiota and prostate cancer development and treatment.

The human gastrointestinal microbiome contains commensal bacteria and other microbiota that have been gaining increasing attention in the context of cancer development and response to treatment. Microbiota play a role in the maintenance of host barrier surfaces that contribute to both local inflammation and other systemic metabolic functions. In the context of prostate cancer, the gastrointestinal microbiome may play a role through metabolism of estrogen, an increase of which has been linked to the induction of prostatic neoplasia. Specific microbiota such as Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectalie, and Mycoplasma genitalium have been associated with differing risks of prostate cancer development or extensiveness of prostate cancer disease. In this Review, we discuss gastrointestinal microbiota's effects on prostate cancer development, the ability of the microbiome to regulate chemotherapy for prostate cancer treatment, and the importance of using Next Generation Sequencing to further discern the microbiome's systemic influence on prostate cancer.

Serum Elabela/Toddler Levels Are Associated with Albuminuria in Patients with Type 2 Diabetes.

BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D). METHODS: An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30-299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence. RESULTS: The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000). CONCLUSIONS: To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.

A Psychophysiological Study of Processing HIV/AIDS Public Service Announcements: The Effects of Novelty Appeals, Sexual Appeals, Narrative Versus Statistical Evidence, and Viewer's Sex.

This study used self-reports and physiological measures-heart rate (HR) and skin conductance level (SCL)-to examine the effects of novelty appeals, sexual appeals, narrative versus statistical evidence, and viewer's sex on cognitive and emotional processing of HIV/AIDS public service announcements (PSAs) among heterosexually active single college students. Novelty or sexual appeals differently affected self-reported attention and cognitive effort as measured by HR. High- rather than low-novelty HIV/AIDS PSAs, perceived as more attention-eliciting, did not lead to more cognitive effort. High- rather than low-sex HIV/AIDS PSAs, not perceived as more attention-eliciting, led to more cognitive effort as reflected by greater HR deceleration. Novelty or sexual appeals also affected self-reported emotional arousal and SCL differently. HIV/AIDS PSAs with high rather than low levels of novelty or sexual appeals led to greater self-reported arousal, but not greater SCL. Message evidence interacted with message appeals to affect cognitive effort. Participants exerted greater cognitive effort during high- rather than low-novelty narrative HIV/AIDS PSAs, and during low- rather than high-novelty statistical ones. The advantage of high over low sexual appeals was more obvious in statistical than in narrative HIV/AIDS PSAs. Males reported greater emotional arousal than females during high- rather than low-sex HIV/AIDS PSAs.

Long-term exposure to cigarette smoke extract induces hypomethylation at the RUNX3 and IGF2-H19 loci in immortalized human urothelial cells.

Cigarette smoking is the single most important epidemiological risk factor for bladder cancer but it is not known whether exposure of urothelial cells to the systemic soluble contents of cigarette smoke is directly causative to bladder cancer and the associated epigenetic changes such as tumor suppressor gene hypermethylation. We undertook this study to investigate if long-term treatment of human urothelial cells with cigarette smoke extract (CSE) results in tumor suppressor gene hypermethylation, a phenotype that was previously associated with long-term constant CSE treatment of airway epithelial cells. We chronically treated an immortalized human urothelial cell line UROtsa with CSE using a cyclic daily regimen but the cells were cultured in CSE-free medium between daily treatments. Bisulfite sequencing and real-time PCR array-based methylation profiling were employed to evaluate methylation changes at tumor suppressor gene loci in the chronically CSE-treated cells versus the passage-matched untreated control cells. The RUNX3 tumor suppressor gene promoter was hypomethylated with a significant increase in proportion of the completely unmethylated haplotype after the long-term CSE treatment; whereas RUNX3 promoter hypermethylation was previously reported for bladder cancers of smokers. Hypomethylation induced by the long-term CSE treatment was also observed for the IGF2-H19 locus. The methylation status at the PRSS8/prostasin and 16 additional loci however, was unaffected by the chronic CSE treatment. Transient CSE treatment over 1 daily regimen resulted in transcriptional down-regulation of RUNX3 and H19, but only the H19 transcription was down-regulated in the chronically CSE-treated urothelial cells. Transcription of a key enzyme in one-carbon metabolism, dihydrofolate reductase (DHFR) was greatly reduced by the long-term CSE treatment, potentially serving as a mechanism for the hypomethylation phenotype via a reduced supply of methyl donor. In conclusion, chronic cyclic CSE treatment of urothelial cells induced hypomethylation rather than hypermethylation at specific loci.

[On establishing comparative reference system for syndrome classification study from the thinking characteristics of syndrome differentiation dependent therapy].

To create a comparative referential system for syndrome classification study by viewing from the thinking characteristics of TCM on syndrome differentiation dependent therapy (SDDT), through analyzing the thinking process of SDDT, and the basic features of disease, syndrome and prescription, combining the basic principles of modern evidence-based medicine and feasibility of establishing integrative disease-syndrome animal model. The practice of creating a comparative referential system based on clinical efficacy of prescription was discussed around syndrome pathogenesis and its relationship with disease and prescription, which was one of the important scientific problems in TCM syndrome study. The authors hold that, it may be one of the available approaches for the present study on integration of disease with syndrome by way of insisting on the thinking pathway of stressing the characteristics of TCM and intermerging with modern scientific design; on taking the efficacy of prescription as the comparative reference system to accumulate and improve unceasingly according to the TCM method of syndrome diagnosis inferred from effect of prescription with reverse thought (i.e., to differentiate syndrome from the effect of prescription), and thus build up the syndrome diagnostic standard on the solid clinical and scientific base.

[Protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms].

OBJECTIVE: To explore the influence of psychological factor on asthma, the protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms. METHODS: Allergy and stress-induced asthma models were established in rats by giving ovalbumin and restraining stress. Radioimmunoassay, enzyme linked immunosorbent assay, in situ hybridization and immunohistochemical method were used to detect plasma corticosterone, IL-4, IFN-gamma, expression of glucocorticoid receptor (GR) mRNA in hippocampus and adrenocorticotropic hormone corticoliberin (CRH) positive neuron in hypothalamus. Optical and electron microscopes were used to observe the morphological changes of pulmonary hilar and hippocampal tissues. RESULTS: Shugan Lifei Recipe (SGLFR) could reduce plasma corticosterone, decrease CRH positive neurons in paraventricular nucleus of hypothalamus, up-regulate the expression of GR mRNA in hippocampus and reduce the injury of hippocampal neuron. SGLFR had certain inhibitive effect on hyperfunction of hypothalamo-pituitary-adrenal cortex (HPA) axis in rats with asthma under stress and could also relieve the pathological changes of the pulmonary hilar tissue. The level of plasma IFN-gamma was increased while the level of plasma IL-4 was decreased in SGLFR-treated group. CONCLUSION: The mechanism of SGLFR in treating the rats with asthma under stress is probably to regulate the hyperfunction of HPA axis and the disorder of immuo-system.

[The effect of four kinds of traditional Chinese herbal compound on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis].

OBJECTIVE: To study the effects of four kinds of traditional Chinese herbal compound, Sini powder, Banxiahoupu soup, Ganmaidazao soup and Guizhigancaolonggumuli soup, on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis. METHOD: Rats were divide into 7 groups: normal group, model 1 and 2 groups, Sini powder group, Banxiahoupu soup group, Ganmaidazao soup group, and Guizhigancaolonggumuli soup group. The behaviors of the rats and their CRH of the hypothalamus, ACTH of plasma and CORT of serum (by the means of radio-immunity) were detected. RESULT: Sini powder could reduce the crossing times of open-field test( P < 0.01) and the contents of CRH and CORT (P < 0.01, P < 0.05); Banxiahoupu soup could extent the still time of tail-hanging test ( P < 0.05) and the content of CRH (P < 0.05); Ganmaidazao soup could prolong the still time (P < 0.05) and reduce the struggle times (P < 0.01) of tail-hanging test and reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05); Guizhigancaolonggumuli soup could reduce the crossing times of open-field test (P < 0.01) , extent the still time (P < 0.05) and reduce the struggle times ( P < 0.01) of tail-hanging test of tail-hanging test, also reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05). CONCLUSION: The four kinds of traditional Chinese herbal compound can increase the ability of anti stress by affect the different taches of the hypothalamus-pituitary-adrenal gland axle and change the stress behaviors, which are based on their respective functions of regulating Qi, dispersing phlegm, tonifying Qi and warming Yang.