Research progress in the application of proteomics technology in brain injury.

The aim of this article is to review the application progress of proteomics technology in brain injury research in recent years, point out the current problems that need to be overcome, and explore the application prospects of proteomics analysis in brain injury. This study also aims to retrieve all literature on brain injury and proteomics and summarize it. Through searching and screening, the widespread application of proteomics technology in the treatment of traumatic brain injury (TBI) and the use of a large number of TBI biomarkers were discovered. The pathways mediated by some biomarkers and the physiological and pathological mechanisms of occurrence were elucidated. The current classification of brain injury is mainly based on subjective evaluation of clinical symptoms, combined with objective imaging. However, its practical value is often limited when applied to prognosis evaluation in brain injury. Proteomics technology can make up for this deficiency and provide a reference for the prevention and treatment of brain injury.

Fear of Deportation and Hispanic Early Adolescent Substance Use: a Moderated Mediation Model of Stress and Hope.

Reports of deportation can create a state of chronic fear in children living in mixed-status immigrant families over their own or a loved one's potential deportation. One indicator of health disparities among youth is elevated rates of alcohol, tobacco, and other drug use (ATOD). Yet little is known about the effects of fear of deportation (FOD) on ATOD or what might promote resilience. We explore the associations between FOD and ATOD use, how stress mediates this relationship, and whether hope moderates the mediated pathway from FOD to ATOD. Participants were 200 first- and second-generation 7th grade Hispanic youth (49% female) assessed across three waves of data. A moderated mediation model tested the indirect effect of FOD on ATOD through stress and whether hope moderated these associations. FOD was measured by the Family Fear of Deportation Scale. Snyder's Children's Hope Scale measured hope. Stress was measured by a short version of Pediatric Psychological Stress Measure. ATOD was adapted from the Monitoring the Future project. FOD was not directly associated with ATOD use. However, this path was fully mediated by stress. Hope significantly moderated the path from FOD to stress such that a one unit increase in hope completely offset the effects of FOD on stress. Hope did not moderate the path from stress to ATOD use. Interventions that increase awareness of deportation trauma, alleviate stress, and promote hope may help prevent, delay initiation into, and/or decrease ATOD among Hispanic first- and second-generation youth.

Spectrophotometric Detection of the BRCA1 Gene via Exponential Isothermal Amplification and Hybridization Chain Reaction of Surface-Bound Probes.

In this work, we demonstrated an ultrasensitive approach with a dual-amplification strategy for DNA assay based on isothermal exponential amplification (EXPAR) and the hybridization chain reaction (HCR). In the presence of target DNA, the hairpin probe DNA (HP1) recognized and partially hybridized with the target DNA to form double-stranded structures containing the full recognition sequences for nicking endonuclease and then initiated EXPAR. Under the reaction of EXPAR, a large number of single-stranded DNA (ssDNA) was produced in the circle of nicking, polymerization, and strand displacement. The resulting ssDNA can bind to the surface-bound probe on the well of the microplate and trigger the hybridization chain reaction, resulting in the production of numerous double-stranded DNA concatamers with biotin labeling. In the presence of streptavidin-conjugated horseradish peroxidase (HRP), the amplified signal can be detected by a spectrophotometer via HRP-catalyzed substrate 3,3'5,5'-tetramethylbenzidine (TMB). This proposed dual-amplification method provides a detection limit of 74.48 aM, which also exhibits good linearity ranging from 0.1 fM to 100 pM.

Universal point-of-care detection of proteins based on proximity hybridization-mediated isothermal exponential amplification.

We have developed a point-of-care (POC) lateral flow biosensor (LFB) for universal protein detection based on a proximity hybridization-mediated protein-to-DNA signal transducer, isothermal exponential amplification (EXPAR) and catalytic hairpin assembly (CHA) with high sensitivity and specificity. In this assay, a protein signal transducer was employed to convert the input protein to the output DNA signal. Antibody conjugated DNA1 was firstly hybridized with the output DNA (DNA3). The binding of antibody conjugated DNA1 and DNA2 to the same protein was able to increase the local concentrations, resulting in strand displacement between DNA3 and DNA2. DNA3 with nicking endonuclease recognition sequences at the 5' end then hybridized with hairpin probe 1 to mediate EXPAR in the presence of nicking endonuclease and polymerase. A large number of single strand DNA were produced in the circle of nicking, polymerization and strand displacement. The resulting ssDNA products were further amplified by CHA to generate double-stranded DNA products. The double-stranded DNA products were detected with a lateral flow biosensor within 5 min. This proposed assay has very high sensitivity and selectivity with a dynamic response ranging from 1 fM to 100 nM, and the detection limit was 0.74 fM. This work provides a universal and simple method for protein detection.

[Influence of coexisting components in Coptidis Rhizoma on excretion of magnoflorine in rat bile, urine, and feces].

Magnoflorine is an important aporphine alkaloid in Coptidis Rhizoma. As reported previously, coexisting components in Coptidis Rhizoma can change the pharmacokinetic characteristics of magnoflorine. To illustrate the interactional links of magnoflorine with its coexisting components in Coptidis Rhizoma, the present study investigated the influence of coexisting components in Coptidis Rhizoma on the excretion of magnoflorine in rat bile, urine, and feces. The rats were dosed with magnoflorine(30 mg·kg~(-1)) and water decoction of Coptidis Rhizoma(equivalent to 30 mg·kg~(-1) magnoflorine) via intragastric administration, and magnoflorine(10 mg·kg~(-1)) by intravenous administration, respectively, and the excretion of magnoflorine in rat bile, urine, and feces in 24 h was observed. The excretion rates of magnoflorine in bile and urine in 24 h were 0.90% and 37.11% respectively after intravenous administration of magnoflorine, which suggested that urination was the main excretive way of magnoflorine. The excretion rates of magnoflorine in feces were 8.77% and 6.18% respectively after intragastric administration of magnoflorine and water decoction of Coptidis Rhizoma, which indicated that defecation was the main excretion route of magnoflorine. The cumulative excretion rates of magnoflorine in the bile, urine, and feces in the Coptidis Rhizoma water decoction group were 77.78%, 79.44%, and 70.47% of those in the magnoflorine group. The results showed that the cumulative excretion rates of magnoflorine in rat bile, urine, and feces were not high, suggesting that magnoflorine was metabolized significantly in rats. The coexisting components of Coptidis Rhizoma could inhibit the excretion of magnoflorine in rat bile, urine, and feces, which was consistent with the decrease in the elimination rate of magnoflorine in the pharmacokinetics of Coptidis Rhizoma water decoction. It indicated interactions between drugs. This study is expected to provide references for the development of magnoflorine-containing new drugs and rational clinical medication of Coptidis Rhizoma.

Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models.

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

Prognostic significance of pretreatment controlling nutritional status score in urological cancers: a systematic review and meta-analysis.

BACKGROUND: Controlling Nutritional Status (CONUT) score is a novel nutrition-based biomarker that has been reported for predicting survival in various cancers. However, the relationship between CONUT score and prognosis of urological cancers remains unclear. Hence, we performed this meta-analysis to evaluate the prognostic significance of CONUT score for patients with urological cancers. METHODS: PubMed, Embase, the Cochrane Library and National Knowledge Infrastructure (CNKI) were systematically searched up to October 2020. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association of CONUT score with overall survival (OS), cancer-specific survival (CSS) and recurrence/disease/progress-free survival (RFS/DFS/PFS) in urological cancers. RESULTS: A total of 12 articles with 13 studies were included in the analysis. Pooled results indicated that increased CONUT score predicted poor OS (HR: 1.78, 95% CI 1.51-2.09, p < 0.001), CSS (HR: 2.14, 95% CI 1.55-2.97, p < 0.001) and RFS/DFS/PFS (HR: 1.57, 95% CI 1.35-1.84, p < 0.001). Subgroup analysis by cancer type revealed that high CONUT score associated with worse OS in renal cell carcinoma (RCC) and urothelial cancer (UC) (HR: 3.05, 95% CI 2.07-4.50, p < 0.001; HR: 1.58, 95% CI 1.32-1.89, p < 0.001). Similar results could be found in CSS (RCC HR: 2.67, 95% CI 1.87-3.81, p < 0.011; UC HR: 1.68, 95% CI 1.09-2.59, p = 0.011) and in RFS/DFS/PFS (RCC HR: 1.96, 95% CI 1.44-2.66, p < 0.001; UC HR: 1.42, 95% CI 1.18-1.71, p < 0.001). CONCLUSIONS: These results illustrated that the high CONUT score may predict worse survival for patients suffering from urological cancers. Therefore, the CONUT score may represent an effective prognostic indicator in urological cancers.

Development and validation of a predictive score for ICU delirium in critically ill patients.

BACKGROUND: The incidence of delirium in intensive care unit (ICU) patients is high and associated with a poor prognosis. We validated the risk factors of delirium to identify relevant early and predictive clinical indicators and developed an optimized model. METHODS: In the derivation cohort, 223 patients were assigned to two groups (with or without delirium) based on the CAM-ICU results. Multivariate logistic regression analysis was conducted to identify independent risk predictors, and the accuracy of the predictors was then validated in a prospective cohort of 81 patients. RESULTS: A total of 304 patients were included: 223 in the derivation group and 81 in the validation group, 64(21.1%)developed delirium. The model consisted of six predictors assessed at ICU admission: history of hypertension (RR = 4.367; P = 0.020), hypoxaemia (RR = 3.382; P = 0.018), use of benzodiazepines (RR = 5.503; P = 0.013), deep sedation (RR = 3.339; P = 0.048), sepsis (RR = 3.480; P = 0.018) and mechanical ventilation (RR = 3.547; P = 0.037). The mathematical model predicted ICU delirium with an accuracy of 0.862 (P < 0.001) in the derivation cohort and 0.739 (P < 0.001) in the validation cohort. No significant difference was found between the predicted and observed cases of ICU delirium in the validation cohort (P > 0.05). CONCLUSIONS: Patients' risk of delirium can be predicted at admission using the early prediction score, allowing the implementation of early preventive interventions aimed to reduce the incidence and severity of ICU delirium.

Chinese college students' ability to recognize facial expressions based on their meaning-in-life profiles: An eye-tracking study.

OBJECTIVE: People can be categorized into one of four meaning-in-life profiles: High Presence High Search (HPHS), High Presence Low Search (HPLS), Low Presence High Search (LPHS), and Low Presence Low Search (LPLS).The main goal of this study is to provide a theoretical explanation for why Chinese people with different meaning-in-life profiles have different mental health levels than Western people, based on their emotional-cognitive-processing ability. METHOD: We adopted eye-movement analysis and recognition-judgment experimental paradigm concerning absolute-recognition judgment and relative-recognition judgment in our study. Moreover, we applied a multifactor and multilevel mixed-experimental design. We selected 118 participants for the experiments from the 788 Chinese college students who responded. RESULTS: Our results showed that HPHS individuals preferred positive-emotion pictures, LPLS individuals preferred negative-emotion pictures, HPLS individuals preferred positive- and neutral-emotion pictures, and LPHS individuals preferred neutral-emotion pictures. Moreover, HPHS individuals were better at accurately processing facial expression from pictures, while LPLS individuals lacked such ability. The fine-processing ability of HPLS and LPHS individuals was lower than that of HPHS yet higher than that of LPLS individuals. Moreover, the features of HPLS individuals were closer to HPHS, while those of LPHS individuals were closer to LPLS. CONCLUSIONS: Our findings support the hypothesis that meaning-in-life profiles have different immediate processing abilities and preferences regarding facial expression recognition and different emotional-cognitive-processing ability.

[Study on bile acid metabolism of sleep-deprived mice regulated by Jiaotai Pills based on LC-MS].

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.

BK polyomavirus infection promotes growth and aggressiveness in bladder cancer.

BACKGROUND: Recent studies have confirmed the integration of the BK polyomavirus (BKPyV) gene into the cellular genome of urothelial carcinomas in transplant recipients, further confirming the correlation between BKPyV and urothelial carcinomas after transplantation. However, the role BKPyV infections play in the biological function of bladder cancer remains unclear. METHODS: We developed a BKPyV-infected bladder cancer cell model and a mice tumor model to discuss the role of BKPyV infections. RESULTS: Our research proves that BKPyV infections promote the proliferation, invasion and migration of bladder cancer cells, while the activation of ß-catenin signaling pathway is one of its mediation mechanisms. CONCLUSIONS: We first described BKPyV infection promotes the proliferation, invasion and migration of bladder cancer. We verified the role of ß-catenin signaling pathway and Epithelial-Mesenchymal Transition effect in BKPyV-infected bladder cancer. These results provide meaningful information towards the diagnosis and treatment of clinical bladder cancer.

Quality home visits: Activities to promote meaningful interactions.

Examination of and support for specific practices that promote high-quality home visiting are essential as family support programs continue to expand across the country. The current study used direct observation of 91 home visits across 41 home visitors to examine relations among interaction partners, content of the interactions, the home-visitors' activities, and quality of home-visitors' practices and family-members' engagement within programs funded by the Maternal, Infant, and Early Childhood Home Visiting program. More time spent in triadic interactions focused on child-related content, as measured by the Home Visit Rating Scale-Revised, was related to higher quality of family engagement in home visits, as measured with the Home Visit Observation Rating Scales. Time spent in adult-focused interactions and administrative tasks, however, was related to lower quality of home-visiting practices and family engagement. Implications for research and practice are discussed.

A medida que los programas de apoyo familiar continúan expandiéndose a lo largo del país, se hace esencial examinar y apoyar prácticas específicas que promueven la alta calidad de las visitas a casa. El presente estudio usó observaciones directas de 91 visitas a casa llevadas a cabo por 41 visitadores con el fin de examinar las relaciones entre la participación de todas las partes involucradas, el contenido de las interacciones, las actividades de los visitadores a casa, y la calidad tanto de las prácticas de los visitadores como de la participación de los miembros de la familia dentro de los programas subvencionados por MIECHV. Más tiempo empleado en interacciones tríadicas enfocadas en contenidos relacionados con el niño, tal como se midió por medio de las Escalas Revisadas de Evaluación de Visitas a Casa (HVOF-R; McBride y Peterson, 1996), estuvo relacionado con más alta calidad de la participación de la familia en las visitas a casa, tal como se midió por medio de las Escalas de Evaluación de la Observación de Visitas a Casa (HOVRS; Roggman et al., 2014). El tiempo empleado en interacciones enfocadas en los adultos y tareas administrativas, sin embargo, estuvo relacionado con más baja calidad de las prácticas de visita a casa y participación de la familia. Se discuten las implicaciones para la investigación y la práctica.

L'examen et le soutien de pratiques spécifiques qui promeuvent la visite à domicile de qualité sont essentiels alors que les programmes de soutien à famille continuent de se développer aux Etats-Unis. Cette étude a utilisé une observation directe de 91 visites à domicile effectuées par 41 visiteurs afin d'examiner les relations entre les partenaires d'interaction, le contenu des interactions, les activités des visiteurs ou visiteuses à domicile, et la qualité des pratiques des visiteurs ou visiteuses à domicile ainsi que l'engagement des membres de la famille au sein des programmes américains de visite à domicile subventionnés par le programme américain Maternal, Infant, and Early Childhood Home Visiting. Plus de temps passé dans les interactions triadiques mettant l'accent sur le contenu lié à l'enfant tel qu'il est mesuré par la version révisée de l'Echelle d'Evaluation de la Visite à Domicile (HVOF-R; McBride & Peterson, 1996) a été lié à une plus grande qualité de l'engagement de la famille durant les visites à domicile telles qu'elles ont été mesurées au moyen des Echelles d'Evaluation de l'Observation de la Visite à Domicile (HOVRS; Roggman et al., 2014). Le temps passé en interactions avec les adultes et en tâches administratives étaient lié à des pratiques de visite à domicile et à un engagement familial de moindre qualité. Les implications pour les recherches et la pratique sont discutées.

Effects of percutaneous endoscopic gastrostomy on survival of patients in a persistent vegetative state after stroke.

AIMS AND OBJECTIVES: To assess the effect of percutaneous endoscopic gastrostomy on short- and long-term survival of patients in a persistent vegetative state after stroke and determine the relevant prognostic factors. BACKGROUND: Stroke may lead to a persistent vegetative state, and the effect of percutaneous endoscopic gastrostomy on survival of stroke patients in a persistent vegetative state remains unclear. DESIGN: Prospective study. METHODS: A total of 97 stroke patients in a persistent vegetative state hospitalised from January 2009 to December 2011 at the Second Hospital, University of South China, were assessed in this study. Percutaneous endoscopic gastrostomy was performed in 55 patients, and mean follow-up time was 18 months. Survival rate and risk factors were analysed. RESULTS: Median survival in the 55 percutaneous endoscopic gastrostomy-treated patients was 17·6 months, higher compared with 8·2 months obtained for the remaining 42 patients without percutaneous endoscopic gastrostomy treatment. Univariate analyses revealed that age, hospitalisation time, percutaneous endoscopic gastrostomy treatment status, family financial situation, family care, pulmonary infection and nutrition were significantly associated with survival. Multivariate analysis indicated that older age, no gastrostomy, poor family care, pulmonary infection and poor nutritional status were independent risk factors affecting survival. Indeed, percutaneous endoscopic gastrostomy significantly improved the nutritional status and decreased pulmonary infection rate in patients with persistent vegetative state after stroke. Interestingly, median survival time was 20·3 months in patients with no or one independent risk factors of poor prognosis (n = 38), longer compared with 8·7 months found for patients with two or more independent risk factors (n = 59). CONCLUSION: Percutaneous endoscopic gastrostomy significantly improves long-term survival of stroke patients in a persistent vegetative state and is associated with improved nutritional status and decreased pulmonary infection. RELEVANCE TO CLINICAL PRACTICE: Percutaneous endoscopic gastrostomy is a promising option for the management of stroke patients in a persistent vegetative state.

cDNA cloning and functional characterisation of four antimicrobial peptides from Paa spinosa.

Antimicrobial peptides (AMPs) are small peptides found in many organisms defending themselves against pathogens. AMPs form the first line of host defence against pathogenic infections and are key components of the innate immune system of amphibians. In the current study, cDNAs of precursors of four novel antimicrobial peptides in the skin of Paa spinosa were cloned and sequenced using the 3'-RACE technique. Mature peptides, named spinosan A-D, encoded by the cDNAs were chemically synthesized and their chemical properties were predicted. The antimicrobial, antioxidative, cyotoxic and haemolytic activities of these four AMPs were determined. While the synthesised spinosans A-C exhibited no activity towards any of the bacterial strains tested, spinosan-D exhibited weak but broad-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria. All peptides were weakly haemolytic towards rabbit erythrocytes, had a strong antioxidative activity, and a low cytotoxic activity against HeLa cells. These findings provide helpful insights that may be useful in the future design of anti-infective peptide agents.

Effects of a 12-hour neuromuscular electrical stimulation treatment program on the recovery of upper extremity function in sub-acute stroke patients: a randomized controlled pilot trial.

[Purpose] This study investigated the effects of a 12-hour neuromuscular electrical stimulation program in the evening hours on upper extremity function in sub-acute stroke patients. [Subjects and Methods] Forty-five subjects were randomized to one of three groups: 12-hour neuromuscular electrical stimulation group (n=15), which received 12 hours of neuromuscular electrical stimulation and conventional rehabilitation for the affected upper extremity; neuromuscular electrical stimulation group (n=15), which received 30 min of neuromuscular electrical stimulation and conventional rehabilitation; and control group (n=15), which received conventional rehabilitation only. The Fugl-Meyer assessment, Action Research Arm Test, and modified Ashworth scale were used to evaluate the effects before and after intervention, and 4 weeks later. [Results] The improvement in the distal (wrist-hand) components of the Fugl-Meyer assessment and Action Research Arm Test in the 12-hour neuromuscular electrical stimulation group was more significant than that in the neuromuscular electrical stimulation group. No significant difference was found between the two groups in the proximal component (shoulder-elbow) of the Fugl-Meyer assessment. [Conclusion] The 12-hour neuromuscular electrical stimulation group achieved better improvement in upper extremity motor function, especially in the wrist-hand function. This alternative therapeutic approach is easily applicable and can be used in stroke patients during rest or sleep.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

[Stability study in biological samples and metabolites analysis of astragaloside IV in rat intestinal bacteria in vitro].

To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites (6-O-ß-D-glucopyranosyl- cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.

[Identification of metabolites of epiberberine in rat liver microsomes and its inhibiting effects on CYP2D6].

Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 µmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.

Exploring the Effect of Anti-immigration Rhetoric on Emergency Department Use by Undocumented Adults.

An unwelcoming policy climate can create barriers to health care access and produce a 'Chilling Effect' among immigrant communities. For undocumented immigrants, barriers may be unique and have a greater impact. We used administrative emergency department (ED) data from 2015 to 2019 for a Midwestern state provided under a data use agreement with the state hospital association. General linear modelling was used to estimate the impact of anti-immigrant rhetoric on ED visit intensity among non-elderly adults who were likely Hispanic/Latino with undocumented status. Compared to 2015, the average ED visit intensity among adults who were likely Hispanic/Latino with undocumented status was significantly higher during 2016-2019 when anti-immigrant rhetoric was heightened. The magnitude of this change increased over time (0.013, 0.014, 0.021, and 0.020, respectively). Additionally, this change over time was not observed in the comparison groups. Our findings suggest that anti-immigrant rhetoric may alter health care utilization for adults who are likely Hispanic/Latino with undocumented status. Limitations to our findings include the use of only those likely to be Hispanic/Latino, data from only one Midwestern state and the loss of data due to non-classification using the NYU ED algorithm. Further research should focus on validating these findings and investigating these identification methods and anti-immigrant rhetoric effects among other undocumented groups including children and adults of different race or ethnicity such as black, both those that identify as Hispanic/Latino and those that do not. Developing strategies to improve health care access for undocumented Hispanic/Latino adults also warrants future research.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.