[Effect of hypophosphatemia on the prognosis of critically ill patients].

OBJECTIVE: To explore the impact of hypophosphatemia on the occurrence and prognosis of critically ill patient. METHODS: The clinical data of critically ill patients admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from October 2021 to April 2022 were retrospectively analyzed. Patients were divided into hypophosphatemia group (serum phosphorus level < 0.80 mmol/L) and non-hypophosphatemia group (serum phosphorus level ≥ 0.80 mmol/L) when they were admitted to the ICU. The following variables were also collected, including gender, age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), serum phosphorus level, serum calcium level, serum magnesium level, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), presence of infection and infection site, length of hospital stay, ICU stay, 28-day mortality, and mechanical ventilation time. Multivariate Logistic regression analysis was used to evaluate the relationship between each variable and the 28-day mortality. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) and 95% confidence interval (95%CI) were calculated to evaluate the predictive value of serum phosphorus levels for the prognosis of ICU patients. RESULTS: A total of 263 patients were enrolled, including 54 patients with hypophosphatemia and 209 patients without. The SOFA score, LYM level and the infection rate of patients in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group [SOFA score: 6.70±3.17 vs. 5.64±3.59, LYM (×109/L): 0.99±0.54 vs. 0.77±0.54, infection rate: 77.78% (42/54) vs. 59.33% (124/209), all P < 0.05], the NLR was significantly lower than that of the non-hypophosphatemia group [10.67 (7.08, 18.02) vs. 12.25 (7.25, 21.68), P < 0.05]. The length of hospital stay, ICU stay, and mechanical ventilation duration in the hypophosphatemia group were significantly longer than those in the non-hypophosphatemia group [length of hospital stay (days): 15 (11, 28) vs. 12 (6, 21), length of ICU stay (days): 10.35±7.80 vs. 7.15±6.61, mechanical ventilation duration (days): 3 (0, 12) vs. 2 (0, 5), all P < 0.05]. There was no significant difference in the 28-day mortality between the hypophosphatemia group and the non-hypophosphatemia group [9.26% (5/54) vs. 11.00% (23/209), P > 0.05]. Multivariate Logistic regression analysis showed that APACHE II score [odds ratio (OR) = 1.188, 95%CI was 1.110-1.271], CRP (OR = 1.016, 95%CI was 1.007-1.026), and NLR (OR = 1.002, 95%CI was 0.996-1.008) were independent risk factors affecting the 28-day mortality of critically ill patients in ICU (all P < 0.05). ROC curve analysis showed that the AUC of serum phosphorus levels for predicting the length of hospital stay of critically ill patients in ICU > 10 days, ICU stay > 5 days, and mechanical ventilation duration > 5 days were 0.701 (95%CI was 0.632-0.770), 0.771 (95%CI was 0.691-0.852), 0.617 (95%CI was 0.541-0.692), respectively, all P < 0.01. CONCLUSIONS: Hypophosphatemia has some predictive value for the length of hospital and ICU stay and mechanical ventilation time in critically ill patients, but it cannot predict the 28-day mortality.

Upregulation of the expression of Toll-like receptor 9 in basophils in patients with allergic rhinitis: An enhanced expression by allergens.

It was reported that the expression of Toll-like receptor (TLR) 9 may be related to Th2-type allergic inflammation including allergic rhinitis (AR). However, little is known about the expression of TLR9 in the basophils in AR. In the present study, the expression of TLR9 was examined by flow cytometry analysis, and the expression of TLR9 mRNA in KU812 was determined by quantitative real-time PCR. The results showed that the percentage of TLR9+ CCR3+ cells in blood granulocytes increased by 46% in patients with AR, but not in peripheral blood mononuclear cells (PBMCs). Allergens namely Dermatophagoide allergen extract (DAE) and Platanus pollen allergen extract (PPAE) upregulated the expression of TLR9 in CCR3+ granulocytes by 76% and 84%, respectively. DAE and PPAE also enhanced the proportions of TLR9+ CD123+ HLA-DR- cells and TLR9+ CCR3+ CD123+ HLA-DR- cells in granulocytes and PBMCs of patients with AR. In order to investigate the actions of allergens on basophils, KU812 cells were used. It was observed that all KU812 cells expressed TLR9, and the expression intensity of TLR9 in a single KU812 cell was elevated by CpG. IL-37, IL-31, IL-33, Artemisia sieversiana wild allergen extract (ASWAE), DAE, OVA and Der p 1 induced an increase in the expression of TLR9 mRNA and IL-6 production in KU812 cells. It was shown that the percentage of TLR9-expressing basophils increased in the blood of ovalbumin (OVA)-sensitized mice. In conclusion, an increased expression of TLR9 and the production of IL-6 in basophils implicate that the contribution of basophils to AR is likely via TLR9.

Real-world data on the dose-related effect of arsenic trioxide in the relapse of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) has become a highly curable disease with all-trans retinoic acid-based regimens. However, following the administration of arsenic trioxide (ATO), the relapse rate remains at 1-10%. It is not known whether the dosage of ATO is associated with the relapse rate in real-world settings. According to 2019 National Comprehensive Cancer Network guidelines, the recommended cumulative ATO dosage in post-remission therapy is 7.95-12 mg/kg in APL. In the current study, 112 patients with newly diagnosed APL receiving a combination of all-trans retinoic acid, anthracycline-based chemotherapy and different dosages of ATO for variable courses, were divided into the high-dose (ATO dosage, ≥12 mg/kg) and low-dose groups (ATO dosage, <12 mg/kg). Relapse risk factors were analyzed by multiple factor analysis. The relationship between relapse rate and ATO dosage in post-remission was elucidated by determining the 4-year cumulative incidence of relapse (CIR). Based on the ATO dosage in post-remission therapy, 72 (64.3%) patients were in the low-dose group and 40 (35.7%) were in the high-dose group. An increased ATO dosage was demonstrated to be an independent protective factor in terms of probability of relapse (P=0.004). With a median follow-up time of 53 months, the 4-year CIR was 16.7% in the low-dose group and 0% in the high-dose group, respectively (P=0.008). No patient relapsed when administered an ATO dosage >6 mg/kg. In conclusion, the relapse rate of APL was significantly associated with ATO dosage in post-remission therapy. An increased ATO dosage may serve as a protective factor of relapse. ATO dosage should therefore reach up to 12 mg/kg, with consideration to reduce the dosage in the future.

Effect of chitosan-gelatin coating containing nano-encapsulated tarragon essential oil on the preservation of pork slices.

There is an increasing demand for bio-based packaging materials incorporated with active nanoparticles as one of the new technologies to obtain food products with improved quality and extended shelf-life. The objectives of this study were to develop a chitosan-gelatin based edible coating incorporated with nano-encapsulated tarragon essential oils (TEO) and to investigate the effects of chitosan-gelatin coatings containing TEO or TEO-loaded nanoparticles (TEO-NPs) on the preservation of pork slices during refrigerated storage for 16 days. Nanoparticles with the average diameters of 246.27-504.60 nm were produced using different mass ratios of chitosan to TEO (1:0, 1:0.2, 1:0.4, 1:0.6, 1:0.8 and 1:1) by ionic gelation method. Zeta potential and encapsulation efficiency (EE) of the prepared TEO-NPs were 27.07-37.12 mV and 9.83-35.57%, respectively. TEO-NPs with the maximum EE were applied for preparing the edible coatings. The results suggested that the coating treatments could significantly inhibit quality deterioration of pork slices. Nano-encapsulation contributed to the sustained release of TEO and caused an improved antioxidant, antibacterial and sensory properties. The study suggests that chitosan-gelatin coating incorporated with TEO-NPs could be developed as a prospective active packaging to preserve pork slices.

Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial.

BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable disease when treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO). The combination of ATO and ATRA has become the standard therapeutic protocol for induction therapy in non-high-risk APL. An oral arsenic realgar-indigo naturalis formula (RIF) has also showed high efficacy and it has a more convenient route of administration than the standard intravenous regimen. Unlike in previous trials, the arsenical agent was used simultaneously with ATRA during post-remission therapy in this trial. METHODS: This study was designed as a multicenter, randomized controlled trial. The trial has a non-inferiority design with superiority being explored if non-inferiority is identified. All patients receive ATRA-ATO during the induction therapy. After achieving hematologic complete remission (HCR), patients were randomly assigned (1:1) to receive treatment with ATRA-RIF (experimental group) or ATRA-ATO (control group) as the consolidation therapy. During the consolidation therapy, the two groups receive ATRA plus RIF or intravenous ATO 2 weeks on and 2 to ~ 4 weeks off until molecular complete remission (MCR), then ATRA and oral RIF 2 weeks on and 2 to ~ 4 weeks off giving a total of six courses. DISCUSSION: This trial aims to compare the efficacy of ATRA-ATO versus ATRA-RIF in non-high-risk patients with APL, to demonstrate that oral RIF application reduces the total hospitalization days and medical costs. The simple schedule was studied in this trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899169. Registered on 14 September 2016.

[Up-regulated expression of NK1R in eosinophil-enriched blood cells from patients with chronic spontaneous urticaria].

Objective To investigate the expressions of substance P (SP) and neurokinin-1 receptor (NK1R) in eosinophil-enriched blood cells from patients with chronic spontaneous urticaria (CSU). Methods Peripheral venous blood samples were collected from patients with CSU and healthy controls (HCs), and then stimulated with crude extracts of Artemisia pollen, dust mite, and Platanus pollen (all at concentrations of 0.1 and 1.0 µg/mL). The expressions of SP and NK1R in eosinophil-enriched blood cells were detected by flow cytometry. Results Compared with HCs, eosinophil proportion in peripheral blood of CSU patients increased 1.2-fold. Percentage of NK1R+ eosinophils in the patients with CSU was elevated up to 66% compared with HCs when cultured in the medium only. However, the level of SP decreased by 40% in the CSU patients. In eosinophil-enriched blood cells from the CSU patients, the crude extract of dust mite at 0.1 µg/mL induced approximately 1.11-fold increase of NK1R expression. Conclusion Expression of NK1R increases in the eosinophils of CSU patients. Blockers of NK1R might be used for CSU treatment.

[Changes of Main Syndromes of Gan Failing to Maintain Normal Flow of Qi in Premenstrual Dysphoric Disorder].

Objective To observe the changes of Chinese medicine (CM) symptoms, the distri- bution characteristics of CM syndromes, and related neuroendocrine levels in premenstrual dysphoric disorder (PMDD) patients. Methods Totally 3 541 female outpatients (18 -45 years old) were inter- viewed by clinical epidemiological questionnaire. According to PMDD diagnostic criteria in DSM-IV , PMDD patients' CM syndromes were identified. Their scores of main symptoms and CM symptoms of common CM syndromes were compared. Contents of 8 neuroendocrine indicators in serum were detected [5- hydroxytryptamine (5-HT) , adrenocorticotropic hormore (ACTH) , angiotensin-II (Ang-II ) , glucocorti- coid (GC), homocysteine (Hcy), melatonin (MLT), nitrogen monoxide (NO), neuropeptide Y (NPY)]. Results Totally 258 PMDD were detected in 3 541 female outpatients (18 -45 years old). The main syn- drome and common syndromes of PMDD patients were reversed invasion of Gan qi syndrome [40.3% (104/258)] and stagnation of Gan qi syndrome [34. 9% (90/258) ], followed by Gan stagnation Pi deficiency syndrome [7.8%(20/258)], Gan stagnation blood stasis syndrome [7.4% (19/258)], Gan stagnation induced fire hyperactivity syndrome [ 6.2% ( 16258 )], Gan stagnation Shen deficiency syndrome [3.1%(8/258)], and Pi-Shen yang deficiency syndrome [0.4%(1258)]. Compared with reversed invasion of Gan qi syndrome, emotional depression and low spirits were main symptoms of stagnation of Gan qi syndrome. Scores for the two symptoms increased (P <0.05). Compared with stagnation of Gan qi syn- drome, irritability, upset, abdominal distension, anxiety, headache, dizziness, insomnia, head distension, bitter mouth, unclear vision were main symptoms of reversed invasion of Gan qi syndrome. Scores for the 10 symptoms increased (P <0.05). Compared with stagnation of Gan qi syndrome, the Hcy level in serum obviously decreased in reversed invasion of Gan qi syndrome (P <0.05). There was no statistical difference in the rest indices (P >0. 05). Conclusions PMDD is closely related to Gan failing to maintain normal flow of qi. Reversed invasion of Gan qi syndrome and stagnation of Gan qi syndrome have different scientif- ic connotations and biological bases. So regulating Gan should be considered as the first choice.

Metabolic profiling of Shu-Yu capsule in rat serum based on metabolic fingerprinting analysis using HPLC-ESI-MSn.

The Chinese herbal formula, Shu-Yu capsule (SYC), has been successfully used to treat depression-like disorders in clinical settings. To rapidly identify the chemical constituents of SYC and its metabolites in rat serum, a simple and sensitive liquid chromatography-tandem mass spectrometry method was established in the present study. By comparing the retention times, MS and MSn spectra data in the literature and reference standards, a total of 73 compounds were identified from SYC. In rat serum, 62 components, including 13 prototype compounds and 49 metabolites were identified. Of these components, 14 metabolites were confirmed as novel metabolites of SYC. The results of the present study indicated that certain flavonoid glycosides and monoterpene glycosides were absorbed directly. Glucuronidation and sulfation were identified as the predominant metabolic pathways of the components in SYC. In addition, certain phase I reactions, including hydrolysis, demethylation and hydroxylation occurred in the rats. These results provide scientific evidence, which support further investigations of the pharmacology and mechanism of SYC.

Analysis of anti-asthmatic drug patents published in China between 2004 and 2013.

INTRODUCTION: We previously reported that 789 anti-allergic patents were granted in China between 1988 and 2008, but the number of patents seems to have grown much faster in China in recent years. Therefore, it is necessary to analyse the patents for anti-asthmatic products between 2004 and 2013 to give pharmaceutical companies and individuals a better understanding of potential candidates for anti-asthmatic drug development from patents published in China. AREAS COVERED: The current report analyses the scientific progress that supports anti-asthmatic drug patent applications and reviews the published patent literature in China from 2004 to 2013. EXPERT OPINION: The rapid increase in the number of anti-asthmatic patents in China indicates that more specific discoveries have been made and that more people are aware of the importance of intellectual property protection in China. Holding patents may guarantee protection for an innovative new product.

Shu­Yu capsule, a Traditional Chinese Medicine formulation, attenuates premenstrual syndrome depression induced by chronic stress constraint.

The present study aimed to investigate the therapeutic effect of the Shu-Yu capsule (SYC), a Traditional Chinese Medicine formulation, on premenstrual syndrome (PMS) depression and the ratio of glutamate (Glu) to γ-aminobutyric acid (GABA) in a rat model of PMS depression. Rats were randomly divided into a control group, model group, fluoxetine group, SYC group and saikosaponins (SS) group. The therapeutic effect of SYC was evaluated using a sucrose preference test (SPT), open field test (OFT) and body mass following four days of treatment. Hippocampal extracellular fluid was collected by microdialysis and the levels of Glu and GABA in the microdialysate were measured by high performance liquid chromatography. The results revealed that, compared with the control group, the sucrose preference coefficient (SC%), total score of OFT and body mass of the model group were significantly lower (P<0.01, P<0.05 and P<0.01, respectively). However, the sucrose preference coefficient, total score of OFT and body mass of the SYC group were all significantly increased compared with the model group (P<0.05). Furthermore, SYC inhibited the decrease of the Glu/GABA ratio in the hippocampus of rats with PMS depression. It was concluded that SYC effectively improved the symptoms of PMS depression, possibly by inhibiting the dysregulation of the Glu/GABA balance in the central nervous system.

Development and thermodynamic evaluation of novel lipid raft stationary phase chromatography for screening potential antitumor agents.

Novel lipid raft stationary phase chromatography (LRSC), with lipid rafts that contain abundant tropomyosin-related tyrosine kinase A receptors immobilized on the stationary phase, was developed for a high-throughput screening of potentially active antitumor agents. Lestaurtinib was used as a model compound to determine the operational parameters of the LRSC. Of all the factors considered, the particle size of column packing, the column temperature and the flow rate were of immense importance in determining the performance of the established LRSC system. In order to profoundly comprehend the binding interaction between the model drug and the receptors on the column, thermodynamic studies were employed. The results revealed that the interaction was spontaneous and exothermic, a typical enthalpy-driven process. Additionally, the primary forces were hydrogen bonding and van der Waals forces. In evaluating the applicability of the method, active extracts from Albizziae Cortex were screened out using the LRSC system under the optimized conditions. The bioactive components were successfully confirmed by the MTT assay. In conclusion, it could be said that the LRSC is a good model for screening potential antitumor agents because of its viability, rapid response and scalable features.

Premenstrual dysphoria and luteal stress in dominant-social-status female macaques.

The current study aims to extend our previous work to develop nonhuman primate model for prospectively studying the mechanism underlying premenstrual dysphoric disorder (PMDD). Thirty young dominant-status female monkeys were randomly divided into the control group, the model group, and JQP group. For two consecutive menstrual cycles, from day 18 to 22, monkeys in the model and JQP groups were housed and immobilized singly in specially designed isolation cages for 5-6 hours per day. At the same time, the pharmaceutical interference effect of jingqianping (JQP) granule, a traditional Chinese medicine specifically used to cure PMDD patients, was tested using monkeys in the JQP group. The behavior and facial expressions of monkeys were photographed with an automatic vidicon and were quantitatively analyzed by "the emotion evaluation scale of female experimental macaque." Changes in serum level of progesterone and estradiol were measured with RIA, and serum level of 5-HT, noradrenaline, and dopamine were measured with HPLC. After experiencing mentioned above stress, 70% of monkeys of model group showed PMDD symptoms during three consecutive menstrual cycles. Estradiol and progesterone serum level decreased (P < 0.01). Moreover, the peak value of secreted hormones in their follicular phase did not occur. Serum level of 5-HT and dopamine were significantly lower (P < 0.01), but the serum noradrenaline level was higher (P < 0.01). Moreover, in monkeys administered by JQP granule, both PMDD symptoms and the anormal serum level of neurotransmitters could be obviously reversed. This special luteal-phase treatment on dominant-social-status monkeys might be a feasible way to create models mimicking PMDD.

[Effects of expression ways and traits of anger emotion on autonomic nerve in the emotion recovery stage].

OBJECTIVE: To explore the effects of expression ways and traits of anger emotion on autonomic nerve in the emotion recovery stage. METHODS: The 48 healthy undergraduate students were recruited as subjects, who were assigned to four groups, i.e., anger-out of high trait group, anger-in of high trait group, anger-out of low trait group, anger-in of low trait group, 12 in each group. The changes of autonomic nerve in emotion recovery stage [mainly including heart rate (HR), finger pulse volume (FPV), heart rate variability (HRV), and galvanic skin response (GSR)] were observed in an experimental paradigm processed dynamically by emotion induction (by watching movie clips) and emotion regulation (by phraseology chewing and regulating body reaction to anger). RESULTS: In the emotion recovery stage all increased data of vegetative reactions decreased in the four groups. The decrease extent of HR, FPV, and GSR was lower in the anger-in groups than that in the anger-out groups (P < 0.05). The HRV showed a decreasing trend, but with no statistical significance (P > 0.05). The decrease extent of HR was lower in the low-anger groups than in the high-anger group (P < 0.05). CONCLUSIONS: Both expression ways and traits of anger exerted influence on the autonomic nerve in the emotion recovery stage. The former influenced more broadly. The influence of anger-in on the autonomic nerve would be more sustainable.

[Effects of jingqianping granule on mRNA and protein expression of mu opioid receptor in premenstrual syndrome gan-qi invasion rats].

OBJECTIVE: To observe the effects of Jingqianping Granule (JG) on mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus of premenstrual syndrome (PMS) Gan-qi invasion rats. METHODS: Twenty rats were selected to prepare the PMS Gan-qi invasion model. After modeling rats were divided into the model group and the Chinese herb treated group, ten in each group. Another 10 rats were selected as the normal control group. During the modeling, JG (1.6 g/kg) was given to rats in the Chinese herb treated group by gastrogavage, while equal volume of normal saline (1 mL/100 g) was given to rats in normal control group and the model group. All treatment was performed once daily for five successive days. The mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus were detected using RT-PCR and Western blot respectively. RESULTS: Compared with the normal control group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively weaker in the model group, and the optical density value decreased. The MOR mRNA and protein expressions in the parietal cortex and the frontal cortex relatively decreased. But the bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively stronger and optic value increased. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively increased with statistical difference (P<0.01, P<0.05). Compared with the model group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively enhanced, the MOR mRNA expression in the parietal cortex increased, the MOR protein expression in the parietal cortex and the frontal cortex increased in the Chinese herb treated group. The bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively weaker. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively decreased. The MOR protein expression in the hippocampus decreased relatively with statistical difference (P<0.01, P<0.05). CONCLUSIONS: Expression of mu opioid receptor in brains of PMS Gan-qi invasion rats was regionally specific. Administration of JG showed corresponding regulatory effects.

Analysis of antibiotic patents issued in China from 1992 to 2011.

INTRODUCTION: The wide use of antibiotics both within and beyond the medical territory plays a significant role in the development of resistant bacteria. Therefore, there is a pressing need for the development of effective antibiotics worldwide. AREAS COVERED: The current analysis report covers the scientific progress in supporting antibiotic patent application and the granted patent literature in China for the last 20 years. EXPERT OPINION: Among the 2780 patents granted in China last 20 years, ß-lactam antibiotics, macrolides, quinolones, aminoglycosides, sulfonamides, glycopeptides and tetracyclines constitute 44.3, 17.4, 13.5, 4.1, 3.8, 3.0 and 2.1% of total patents, respectively. Scientists have faced challenges in developing new antibiotics against increasingly growing types of drug-resistant bacteria, which may causes serious global public health disaster in future. Poor financial investment in antibiotic research has exacerbated the situation. Therefore, new antibiotic patents will be applied continuously. The combination individual ß-lactam antibiotics with a ß-lactamase inhibitor have been demonstrated clinically beneficial and may suggest a new way for the development of more effective antibiotics in future. Local patent applications of China are stably increasing largely through a dependence on the imitation of Western drugs. The current study may help to better understand the patent situation in China and to invent the more efficient antibiotic therapies.

Syndrome evaluation in traditional Chinese medicine using second-order latent variable model.

The syndrome is one of the most important concepts and ingredients in the theoretical and clinical research of traditional Chinese medicine (TCM). TCM doctors believe that all diseases are caused by an imbalance in the patient's body, which is called syndrome. All the therapies and formulas in TCM are decided according to the patients' syndrome situation. To quantitatively evaluate the level of syndrome, many statistical methodologies have been discussed in recent years. In this article, we introduce a second-order latent variable model to evaluate the level of patients' syndrome with many clinical symptoms. An objective evaluation score can be easily derived by the proposed model, with a high speed of convergence and without joint-distribution assumption. We illustrate the application of this model by an analysis of premenstrual disorder syndrome of liver-qi invasion syndrome evaluation research.

[Effects of Chinese herbal medicines for regulating liver qi on expression of 5-hydroxytryptamine 3B receptor in hypothalamic tissues of rats with anger emotion].

OBJECTIVE: To explore the central mechanisms of anger emotion and the effects of Chinese herbal medicines for regulating liver qi on the anger emotion and the expression level of 5-hydroxytryptamine 3B receptor (5-HT3BR) in rat hypothalamus. METHODS: Rat models of anger-in or anger-out emotions were prepared by the methods of resident intruder paradigm. There were five groups in this study: control, anger-in model, Jingqianshu Granule-treated anger-in, anger-out model and Jingqianping Granule-treated anger-out groups. The treatment groups were orally given Jingqianshu granules and Jingqianping granules respectively, and the model groups and the normal control group were given sterile water. Open-field test and sucrose preference test were used to evaluate behavioristics of the rats. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot methods were used to detect the expression levels of 5-HT3BR mRNA and protein in the rat hypothalamus. RESULTS: The expression of 5-HT3BR in hypothalamus of anger-in model rats increased obviously (P<0.01) and that of anger-out model rats decreased obviously (P<0.01) compared with the normal control group. Compared with the model group, the expressions of 5-HT3BR in the treatment groups were significantly improved (P<0.01) after treatment, and recovered to normal level. CONCLUSION: The anger-in stimulation obviously increases hypothalamic 5-HT3BR expression and the anger-out emotion can obviously reduce its expression. Chinese herbal medicines for regulating liver qi may treat anger emotion in rats by improving the hypothalamic 5-HT3BR protein and gene expression levels.

Ferulic acid-induced anti-depression and prokinetics similar to Chaihu-Shugan-San via polypharmacology.

Selective serotonin reuptake inhibitors (SSRIs), one of popular antidepressants as "one-compound-one-target" paradigm, cannot but discontinue because of inhibiting gut movement. Traditional Chinese medicine (TCM) Chaihu-Sugan-San (CSS) can simultaneously exert anti-depression and prokinetics. From this thread, we aimed to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between CSS and its absorbed compound ferulic acid (FA) were made. And FA's action mechanisms involved in monoaminergic systems, HPA axis and gastrointestinal peptide ghrelin was then studied in forced swimming test (FST) of rat. Lastly, the jejunal contraction activity evoked by FA was measured in vitro. Compared with vehicle, FA reduced immobility time, increased locomotor activity, accelerated gastric emptying and intestinal transit similar to CSS whose absorbable component FA was identified in hippocampus and jejunum. FA's prokinetics in vivo was further supported by its jejunal contraction in vitro. FA-induced anti-immobility was prevented by pretreated with PCPA, WAY-100635, ketanserin, sulpiride, SCH233390, haloperidol and yohimbine, respectively. CRH, ACTH and 5-HT were significantly decreased, but ghrelin was apparently increased compared with vehicle. In summary, FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously.

[Treatment of premenstrual syndrome with Chinese medicine formula, baixiangdan capsule: implications for neuron viability and GABA(A) receptor modulation in rat cortex].

OBJECTIVE: To explore the effects of Baixiangdan capsule (BXD), a Chinese medicinal formula, on the premenstrual syndrome (PMS) rats with Liver-qi invasion and the possible underlying micro-mechanisms. METHOD: Wistar rats were randomly assigned to two groups, nomal group and BXD group After evaluated by macro-behavior observation and open-field test, MTT assay and the whole-cell patch clamp recording were performed respectively to evaluate the effects of serum from BXD capsule-treated rats on the viability and GABA(A) R-induced currents of cortical neurons in vitro. RESULT: In the open-field test, the crossing score, rearing score and total score of BXD rats decreased significantly (P < 0.05), compared by the normal rats. Compared with cells exposed to serum of normal rats, the viability values of those incubated with serum of BXD group for 24 h and 48 h significantly increased (P < 0.05), measured by MTT assay. The results of whole-cell patch clamp recording showed that concentration-response relationship curves revealed an EC50 value of (29.0 +/- 4.4) micromol x L(-1) and a Hill coefficient of 1.07 for normal-exposed cultures, (63.5 +/- 8.2) micromol x L(-1), 1.04 for BXD-exposed cultures after incubation for 24 h. Furthermore, the difference in EC50 values was statistically significant (P < 0.01), that in the Hill coefficient was not obvious. CONCLUSION: BXD capsule could significantly decrease crossing score and total score of open-field test and effectively enhance the neuron viability and GABA(A) receptor activity in rat cortex. Paeonimetabolins I and paeonol may play a significant role in treating PMS model rats with Liver-qi invasion by BXD capsule, and paeonol may target at GABA(A) receptor, especially.