A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Asari Radix et Rhizoma （ARR） is a traditional Chinese medicine for relieving exterior syndrome， and its roots and stems contain rich chemical components， including volatile oils （terpenoids， aromatics and aliphatics）， lignans， flavonoids， etc. Clinically， it has been traditionally used for the treatment of diseases such as phlegm and cough， anemofrigid cold， rheumatic arthralgia due to its ability to spread cold. Modern pharmacological studies have shown that ARR played beneficial roles in analgesic， anti-inflammatory， antitussive， antiasthmatic， antiviral， antibacterial， sedative， antioxidative， and antidepressant responses， antihypertension， as well as tumor suppression. The current studies on the chemical composition of ARR mainly focused on volatile components， and little information is available for the occurrence and pharmacological effects of non-volatile components. In addition， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts and the origin of species. Therefore， in this study， the authors reviewed a large number of literature on the chemical compositions and pharmacological effects of ARR， and hoping to provide a reference for further pharmacological research and the new drug development of ARR.

OBJECTIVE: A study was conducted to systematically evaluate the clinical efficacy of inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. METHODS: We searched the databases of CNKI, Wanfang, CBM, PubMed, Embase, and Cochrane Library from inception to December 2019. Two reviewers independently collected all literature related to inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. These factors include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature was screened according to the inclusion and exclusion criteria. The quality of the studies was strictly evaluated, and the data were extracted. The literature of randomized controlled trials in accordance with the standards was Meta-analyzed with Revman 5.3 software. RESULTS: Six randomized controlled trials were included. Compared with the control groups, the results of meta-analysis showed that non-surgical periodontal therapy significantly reduced the levels of CRP [MD=-0.58, 95%CI (-1.13, -0.02), P=0.04] and IL-6 [MD=-2.76, 95%CI (-5.15, -0.37), P=0.02] in these patients but not that of TNF-α [MD=-3.87, 95%CI (-8.79, 1.05), P=0.12]. CONCLUSIONS Simultaneous regular renal treatment and non-surgical periodontal therapy can help relieve the periodontal damage on patients with chronic kidney disease and periodontitis. Moreover, it can improve the status of some inflammatory factors. This finding is conducive to the control and treatment of chronic kidney disease and periodontitis and needs to be a focus of research and in clinical operation.
C-Reactive Protein ; Chronic Periodontitis ; Humans ; Interleukin-6 ; Renal Insufficiency, Chronic/therapy* ; Tumor Necrosis Factor-alpha

OBJECTIVE: To explore the effect of electroacupuncture treatment on the levels of cortisol and immune factors in patients with occupational noise-induced deafness(ONID) combined with depressive symptoms. METHODS: A total of 78 ONID patients combined with depressive symptoms were randomly divided into control group(40 cases) and electroacupuncture group(38 cases) by a random number table method. The control group received routine therapy, while the electroacupuncture group was treated with routine therapy plus electroacupuncture on alternate days, 3 times a week for 4 consecutive weeks. The levels of salivary cortisol, as well as the serum levels of cortisol, tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and C-reactive protein(CRP) of the two groups were observed and compared before and after treatment. RESULTS: Before treatment, the levels of saliva cortisol in the morning and night, and the serum levels of cortisol, IL-6, TNF-α and CRP in the two groups were compared, and the differences were not statistically significant(P>0.05). After treatment, the serum cortisol level of patients in electroacupuncture group reduced than that before treatment in the same group(P<0.05). However, there was no significant difference in the levels of salivary cortisol in the morning and night, and serum cortisol before and after treatment both in control group and electroacupuncture group(P>0.05). After treatment, the serum levels of IL-6 and TNF-α decreased in electroacupuncture group as compared with those before treatment and those after treatment in control group(P<0.01). CONCLUSION: Electroacupuncture treatment could reduce the levels of TNF-α and IL-6 in serum of ONID patients combined with depressive symptoms. The regulation of electroacupuncture on the inflammatory cytokines may be one of the mechanisms in treating ONID combined with depressive symptoms.

OBJECTIVE: To explore the status and its influencing factors of anxiety symptoms in patients with occupational noise-induced deafness(ONID). METHODS: A total of 220 ONID patients were selected as the ONID group,and 200 healthy participants without noise exposure were selected as the control group by judge sampling method.The two groups were investigated by the Self-Rating Anxiety Scale, Self-Rating Depression Scale and Pittsburgh Sleep Quality Index. The Tinnitus Handicap Inventory was used to evaluate the disability levels of tinnitus, and pure-tone audiometry was used to assess the degree of tinnitus and hearing impairment in the ONID group. RESULTS: The incidence of anxiety, depression, and sleep disorder were higher in the ONID group than that in the control group(52.7% vs 9.0%, 55.0% vs 15.0%, 52.3% vs 7.0%, P<0.05). In ONID with anxiety subgroup, the duration of disease was longer(1.0 vs 2.0 years, P<0.01), incidences of tinnitus, depression and sleep disorder were higher than those in ONID without anxiety subgroup(92.3% vs 100.0%, 18.3% vs 87.9%, 19.2% vs 81.9%, P<0.01). The result of multivariate logistic regression analysis showed that the longer the duration of disease and the more severe of the tinnitus, the higher the risk of anxiety symptoms in patients with ONID [the odds ratio(OR) and its 95% confidence interval(CI) were 1.35(1.10-1.65) and 2.94(1.56-5.54) respectively, P<0.01]. The risk of anxiety in patients with sleep disorders was higher than those without sleep disorders [OR(95%CI) was 12.78(5.90-27.64), P<0.01]. CONCLUSION: The ONID patients are more likely to have anxiety. The duration of disease, severity of tinnitus and sleep disorders are the risk factors causing anxiety in ONID patients.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

Objective:To investigate the effect of endothelin-1 (ET-1) on the expression of phosphorylated myosin light chain Ⅱ(p-MLCⅡ)and myosin light chain Ⅱ(MLCⅡ)protein in rat hepatic stellate cells HSC-T6 and explore the intervention effect of Danggui Shaoyao San(DSS)drug-containing serum. Method:After HSC-T6 cells were seeded, DMEM and blank rat serum with final concentrations of 2.5%, 5%, 10%, 15% and 20% were added to each well. The viability of HSC-T6 cells was determined by methyl thiazolyl tetrazolium(MTT) assay to screen the suitable serum concentration range. The cells were divided into blank serum control group (5%, 10%, 15%) and DSS drug-containing serum group (5%, 10%, 15%). ELISA was used to detect the content of ET-1 in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), DSS drug-containing serum low (5%), medium (10%) and high dose (15%) groups. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the level of ET-1 mRNA in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), model group (10%), DSS drug-containing serum low (5%), medium (10%), high dose (15%) groups and Y-27632 inhibitor group (100 μmol·L^-1). Except the blank serum control group, the other groups all received 10 nmol·L^-1 ET-1 to induce HSC-T6 cells. Western blot was used to detect the expression of p-MLCⅡ and MLCⅡ in HSC-T6 cells induced by ET-1. Result:Serum concentrations of 5%, 10% and 15% were used as drug-containing serum concentrations. As compared with the blank serum control group, the DSS drug-containing serum group significantly reduced the relative content of ET-1 and ET-1 mRNA in the basic state (P<0.05, P<0.01). As compared with the blank serum control group, the expression of p-MLCⅡ and MLCⅡ protein in the model group was significantly increased (P<0.01); DSS drug-containing serum groups and Y-27632 inhibitor group can significantly down-regulate p-MLCⅡ and MLCⅡ protein expression (P<0.05, P<0.01). Conclusion:DSS drug-containing serum may down-regulate the expression of p-MLCⅡ and MLCⅡ by down-regulating the content of ET-1 and inhibiting the autocrine of ET-1.

Lilii Bulbus, which comes from many medicinal plants，is a frequently-used traditional Chinese medicine，the records in previous herbal literatures of it's origin and quality were inconstant. To trace back it's sources, we conducted a systematical study on it's origin and quality by textual research and investigation in this paper,The result showed that the origins of Lilii Bulbus are mainly source from white-flowers, red-yellow-flowers and red-flowers of Lilium， L. brownii var. viridulum, which were believed authentic or good quality in all previous herbal literatures,and L. pumilum and L. concolor which belong to white-flowers,and L. lancifolium which belong to red-yellow-flowers were believed low-quality and unfit for medicinal uses, or they were listed below and often have different effect with L. brownii var. viridulum. Among them, only L. concolor does not belong to Lilii Bulbus according to Chinese Pharmacopeia (2015 edition), The mainstream varieties of Lilii Bulbus became L. lancifolium now according to our practical investigation, which were very different from previous herbal literatures. Although chemical and pharmacological studies provided a reference for L. lancifolium，we should respect the actual records of the previous herbal literatures，the research of material foundation of efficacy should be more sufficient，and provide science evidence for clinical application of different species of Lilii Bulbus.

OBJECTIVE: To predict the sensitizing potency and optimal sensitization dose of trichloroethylene( TCE) by an in vitro skin sensitization test on a human acute monocytosis cell line( THP-1).METHODS: THP-1 cells were cultured in vitro and exposed to 2,4-dinitrochlorobenzene( DNCB),sodium dodecyl sulfate( SDS),tert-butylhydroquinone( tBHQ)and TCE for 24 hours.Flow cytometry was used to detect the expression of cell surface marker such as cluster of differentiation( CD) 86 and CD54,and the optimal dose range for sensitization detection was determined.With the relative fluorescence intensity( RFI),CD86 ≥ 150 and CD54 ≥ 200 as the standard,the sensitizing potency and optimal sensitization dose of TCE were predicted.RESULTS: The concentration range of reagents for sensitization test on THP-1 cells was the dose range at which the relative cell survival rate reached 75.0%-100.0%.DNCB at the doses of 20.83,25.00 and 30.00 μmol/L,tBHQ at the dose of 5.80 μmol/L,TCE at the doses of 8.33,10.00 and 12.00 mmol/L,can cause sensitivity.SDS was recognized as a negative sensitizer.The expression of CD86 and CD54 was the highest when the concentration of TCE was 8.33 mmol/L,which was considered as the best sensitization dose.CONCLUSION: The optimum sensitization dose of TCE is 8.33 mmol/L,which can provide the basis for dose design in future study of TCE sensitization pathways.