Objective: To provide references for optimizing adjuvants with Polygoni Multiflori Radix (PMR), we compared the effects of detoxification by different adjuvants processing according to Chinese medicine’s records of past dynasties. Methods: The chemical information of all samples including crude and processed PMR with different adjuvants was characterized by UPLC-Q-TOF-MS, and the normal human hepatocytes (L02 cell line) was cultured in vitro to evaluate the cytotoxicity, then we gave synthetic analyses on effects of processed PMR with different adjuvants for toxicity-decreasing and variations of chemical contents. The difference of toxicity reducing effect and the rule of composition change of PMR processed with different adjuvants were compared comprehensively. Results: Different adjuvants had different level of effects on chemical fingerprint, index component and cytotoxicity of PMR under the same conditions of pressure and time. More specifically, black bean, jujube and rice-rinsing water had greater impact on PMR main components including gallic acid, catechins, cis-stilbene glycoside, trans-stilbene glycoside, emodin-8-O-β-D-glucoside, physcion and emodin as well as hepatotoxicity. The three adjuvants with the best toxicity-decreasing effects were in sequence of rice-rinsing water > jujube > black bean. Furthermore, comprehensive analysis of simple correlation and multiple correlation suggested that cis-stilbene glycoside might be the main chemical component contributed to hepatotoxicity of PMR, and emodin-8-O-β-D-glucoside might be the potential toxicity component. Conclusion: Different adjuvants traditionally recorded can attenuate the toxicity of PMR. In addition to black beans, rice-rinsing water and jujube can also be used as candidate adjuvants for the toxicity-decreasing of PMR.

Hepatic fibrosis models were induced by CCl4 in rats. To explore vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGFβ1) mRNA expression and bcl-2, Bax protein expression levels of intervention and explore the mechanism of the Aralia chinesis anti-hepatic fibrosis. Sixty male Sprague-Dawlley (SD) rats were randomly divided into six groups: nomal group, model group, high-dose (10 mL x kg(-1)), medium-dose (7.5 mL x kg(-1)), low-dose (5.0 mL x kg(-1)) of A. chinesis treated group and colchicine treated group. The change of liver histopathology was observed by HE and Masson staining. The mRNA of VEGF, TGF-β1 were detected by RT-PCR. The protein of Bcl-2 and Bax were detected by Western blot. In the model group liver cell obvious degeneration, necrosis, a large number of collagen fibers of the cable hyperplasia, part visible pseudolobule formation. A. chinesis large, medium, low-dose group and colchicine group liver cell degeneration and necrosis reduced A. chinesis small, medium, and high-dose group was gradually reduced trend and A. chinesis large, middle dose group degree of reduction is particularly significant. Compared with model group, A. chinesis of large, medium and small dose group and colchicine group VEGF mRNA expression, A. chinesis of large, medium-dose group TGF-β1 mRNA expression reduce (P < 0.05); compared with colchicine group, A. chinesis of large, middle dose group of VEGF mRNA expression decreased (P < 0.05); A. chinesis of large, middle dose group of TGF-β1 mRNA expression decreased (P < 0.01), and compared with colchicine group, large dose group of of TGF-β1 mRNA expression decreased (P < 0.05). Compared with model group, A. chinesis of large, medium and small dose group and colchicine group Bcl-2 protein expression reduce (all is P < 0.05). But A. chinesis of large, medium and small dose group and colchicine group of Bax protein expression were increased (P < 0.05). A. chinesis regulation of VEGF, TGF-β1 may prevent the activation of hepatic stellate cells, liver tissue by up regulating the anti-apoptotic protein Bax and down pro-apoptotic protein Bcl-2 expression, thereby to improve the degree of liver fibrosis.
Animals ; Apoptosis ; drug effects ; Aralia ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; Hepatic Stellate Cells ; drug effects ; metabolism ; Humans ; Liver Cirrhosis ; drug therapy ; genetics ; metabolism ; Male ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo explore the effect of Shoutai Pill (STP) containing serum on bioactivity behaviors of trophoblast cells in spontaneous abortion (SA) patients such as cell proliferation, invasion, migration and secretion.

METHODSTrophoblast cells in artificial abortion in normal pregnancy and SA patients were isolated and cultured in vitro, which were then treated with STP containing serum at various concentrations (5%, 10%, 20%, respectively). Blank serum was taken as the normal control group and dydrogesterone containing serum as the dydrogesterone control group. The proliferation, cycle distribution, invasion and migration capacity, and beta human chorionic gonadotropin (p-HCG) level were detected by methyl thiazolyl tetrazolium (MTT) colorimetry, flow cytometry (FCM), Transwell experiments, and ELISA, respectively.

RESULTSCompared with the normal control group, the activity of cell proliferation obviously decreased, ratios of apoptotic cells (SubGO/G1) and G2/M phase were obviously elevated, S phase cell ratio was obviously reduced (all P < 0.05). Transwell experiments indicated invasion and migration capacity obviously decreased, secreted beta-HCG level were obviously reduced after 72-h intervention (P < 0.05). Compared with the SA group, the activity of cell proliferation obviously increased, ratios of apoptotic cells and G2/M phase were obviously reduced, S phase cell ratio was obviously elevated, invasion and migration capacity were obviously enhanced, secreted beta-HCG level were obviously elevated after 72-h intervention in the dydrogesterone control group and each STP containing serum group (all P < 0.05). The activity of trophoblastic cell proliferation, S phase cell ratio, invasion and migration capacity, and secreted beta-HCG level were strengthened along with increased STP containing serum. Besides, the effects of 20% STP containing serum group were significantly superior to those of the dydrogesterone control group (P < 0.05).

CONCLUSIONSTP containing serum could dose-dependently enhance the proliferative activity of trophoblastic cells, invasion and migration capacity, secretion of beta-HCG, and reduce the apoptosis of trophoblast cells, which might be one of mechanisms for STP preventing and treating SA.

Abortion, Spontaneous ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Dydrogesterone ; pharmacology ; Female ; Humans ; Pregnancy ; Trophoblasts ; drug effects

Objective To investigate the effects of ciyelosporine-A(CsA).a calcinenrin(CAN)inhibitor,on electrophysiological propertiesof atria in canine tachycardia-induced model of AF.Methods Eighteen healthy adult mongrel canines weighing 17.0 to 23.2 kg(rangedfrom 2 to 4 years old)were randomized to 3 groups,Sham group(no pacemaker was implanted),atrial tachypacing group(ATP group)each group at baseline and after 8 weeks' tachypacing.Measurements included atrial effective refractory period(AERP),conductionvelocity(CV),wave length(WE),atrial fibrillation load and rate-adaptability. Results After 8 weeks' atrial tachypacing,ATP andCsA groups showed significant longer duration of the P wave,shorter AERP,decreased adaptation of AERE slower CV,shorter Wland longer AF duration compared to the shamg roup (all P＜0.05).AERP of the CsA group was longer than that of ATP group (P＜0.05),but there were no differences in rate-adaptability,CV,incidence of induced AF and AF duration between CsA group and ATP group.Conclusions Our results suggest that calcineurin pathway intervention by CsA have a positive effect on tachycardia-inducedelectrical remodeling of atria,but can not prevent or reverse AF.

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

Objective: To observe the effects of moxibustion at Shenshu (BL 23), Zusanli (ST 36) and Shenque (CV 8) on the energy metabolism and endocrine metabolism indicators of rats undergoing one-time exhaustive swimming, and to explore the differences between moxibustion at different points in the effects on anti-exercise fatigue. Methods: Forty-eight male SPF rats were randomly divided into a blank group, a model group, a non-meridian and non-acupoint group, a Shenshu (BL 23) group, a Zusanli (ST 36) group, and a Shenque (CV 8) group using random number table method, with eight rats in each group. Except for the blank group, rats in the other groups were subjected to replicating the one-time exhaustive model using the weight-bearing swimming experiment. Except for the model group, the other model rats received mild moxibustion immediately after swimming. Rats in the non-meridian and non-acupoint group received mild moxibustion at bilateral subcostal non-meridian and non-acupoint points, those in the Shenshu (BL 23) group received mild moxibustion at bilateral Shenshu (BL 23), those in the Zusanli (ST 36) group received mild moxibustion at bilateral Zusanli (ST 36), and those in the Shenque (CV 8) group received mild moxibustion at Shenque (CV 8) for 15 min. Four hours after the exhaustive swimming, femoral artery blood was collected to detect blood lactate (BLA), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRE), blood urea nitrogen (BUN), cortisol (C) and testosterone (T) levels, and calculate the T/C ratio. Results: Compared with the blank group, rat's serum levels of BLA, LDH, CK, BUN and C in the model group and the non-meridian and non-acupoint group were increased, and serum levels of CRE and T, and T/C ratios were decreased (P<0.01 or P<0.05); compared with the model group and the non-meridian and non-acupoint group, the serum levels of BLA, LDH, CK, BUN and C in the Shenshu (BL 23) group, Zusanli (ST 36) group and Shenque (CV 8) group were decreased, and the serum CRE and T levels, and the T/C ratios were increased (all P<0.01); compared with the Shenshu (BL 23) group, the serum CK level was decreased in the Shenque (CV 8) group (P<0.01), the serum levels of T and C were decreased in the Zusanli (ST 36) group and Shenque (CV 8) group (P<0.01 or P<0.05), and the T/C ratio was increased in the Shenque (CV 8) group (P<0.01); compared with the Zusanli (ST 36) group, the serum CK and BUN levels were decreased (P<0.01, P<0.05), and the T/C ratio was increased in the Shenque (CV 8) group (P<0.05). Conclusion: Moxibustion at Shenshu (BL 23), Zusanli (ST 36) and Shenque (CV 8) shows different anti-fatigue effects by regulating the energy metabolism and endocrine metabolism in rats undergoing one-time exhaustive swimming. Moxibustion at Shenshu (BL 23) is better in promoting energy synthesis. Moxibustion at Shenque (CV 8) is more effective in regulating synthesis and decomposition of the skeletal muscle proteins.

OBJECTIVETo explore changes of B and T lymphocyte attenuator (BTLA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAOC), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA) in ankylosing spondylitis (AS) patients, and the effect of Xinfeng Capsule (XFC) on them.

METHODSTotally 120 AS patients were assigned to two groups according to random digit table method, the XFC group (3 XFC pills each time, 3 times a day) and the SASP group (4 SASP tablets each time, twice a day), 60 in each group. All patients were treated for 3 months. Another 60 healthy subjects were recruited as a healthy control group. The expression frequency and activation levels of BTLA were detected using flow cytometry. Serum oxidative stress indices (such as SOD and CAT, TAOC, ROS, RNS, MDA) and contents of cytokines [tumor necrosis factor α (TNF-α), IL-1β, IL-4, and IL-10] were detected using enzyme-linked immunoassay (ELISA). Erythrocyte sedimentation rate (ESR) was detected using Westergren method. High-sensitivity C-reactive protein (Hs-CRP) was detected using HITACHI 7060 type automatic biochemical analyzer. Clinical efficacies of ASAS 20 and BASDAI50 were assessed using VAS. Correlation analysis between scoring for quality of life and BTLA expression frequency was performed.

RESULTS(1) Clinical efficacies of ASAS 20 and BASDAI50 were significantly better in the XFC group than in the SASP group (P < 0.01). (2) Compared with the healthy control group, BTLA expressions in the peripheral blood of AS patients decreased significantly (P <0. 05); SOD, CAT, and TAOC values significantly decreased (P < 0.01, P < 0.05); ROS, RNS, and MDA values significantly increased (P < 0.01, P < 0.05); TNF-α, IL-1β, ESR, and Hs-CRP values significantly increased (P < 0.01); IL-4 and IL-10 values decreased significantly (P < 0.01, P < 0.05). (3) Compared with pre-treatment in the same group, BTLA/CD19 + B, BTLA/CD24 + B, SOD, TAOC, IL-4, SF-36 [physical functioning (PF), social functioning (SF), role limitation due to physical problems (RP), role limitation due to emotional problems (RE), body pain (BP), mental health (MH), vitality (VT), general health (GH)] were significantly elevated; ROS, MDA, TNF-α, ESR, Hs- CRP, VAS, BASDAI and BASFI, BAS-G were significantly lower in the peripheral blood of the two groups after treatment (P < 0.01, P < 0.05). Better effect was shown in the XFC group in elevating BTLA/CD19+ B, BTLA/CD24 + B, SOD, TAOC, IL-10, BP, MH, VT, and SF; and lowering ROS, IL-1β, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI, and BAS-G (P < 0.01, P < 0.05). (4) Pearson correlation analysis showed, BTLA/CD19 + B expression of the peripheral blood was positively correlated with SOD, CAT, TAOC, IL-4, IL-10, GH, RP, BP, and SF (r = 0.431, 0.325, 0.318, 0.316, 0.348, 0.314, 0.358, 0.318, 0.326, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, MDA, TNF-α, IL-1β, ESR, VAS, and BASDAI (r = -0.342, -0.368, -0.334, -0.354, -0.324, -0.372, -0.342, respectively, P < 0.05, P < 0.01). BTLA/CD24 B expression of the peripheral blood was positively correlated with SOD, TAOC, IL-4, IL-10, GH, RP, BP, SF, RE, MH, VT (r = 0.358, 0.352, 0.372, 0.436, 0.435, 0.326, 0.352, 0.345, 0.326, 0.343, 0.332, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, RNS, MDA, ESR, Hs-CRP, VAS, BASDAI, and BASFI (r = -0.447, -0.336, -0.405, -0. 395, -0. 358, -0.436, -0.338, -0.425, respectively, P < 0.05, P < 0.01).

CONCLUSIONXFC could improve BTLA expression in the peripheral blood of AS patients, negatively regulate activation and proliferation of B cells, and reduce abnormal immune responses and oxidative stress injury, thereby effectively alleviating joint stiffness and pain.

B-Lymphocytes ; physiology ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Capsules ; Catalase ; metabolism ; Cytokines ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Flow Cytometry ; Humans ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-4 ; metabolism ; Malondialdehyde ; metabolism ; Oxidative Stress ; Quality of Life ; Reactive Oxygen Species ; Spondylitis, Ankylosing ; drug therapy ; Superoxide Dismutase ; metabolism ; T-Lymphocytes ; physiology ; Tumor Necrosis Factor-alpha ; metabolism

Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.

Objective To summarize and analyze the epidemiological and clinical characteristics of COVID-19 Omicron variant cases in makeshift hospital, and the influence of age, sex and vaccination status on the disease duration, so as to provide reference for the prevention and control of the COVID-19 epidemic. Methods The epidemiological and clinical characteristics of COVID-19 cases admitted to makeshift hospital of National Convention and Exhibition Center (Shanghai) from April 9 to May 31, 2022 were retrospectively described and analyzed, and further cohort analysis was conducted to determine the influence of age, sex and vaccination status on the disease duration of COVID-19 cases in the author's branch hospital. Results Among the 174 466 COVID-19 cases in makeshift hospital, most of them were male, accounting for 59.38%. The infected cases were mainly young and middle-aged people aged 18-59 years old, accounting for 83.50%, followed by 12.30% of the elderly group over 60 years old; the average hospital stay was 7.40 days; the proportion of patients with fever was less than 27.79%; 15.37% (26 817/174 466) of the patients complicated with underlying diseases, and the top three were hypertension, diabetes and coronary heart disease. The proportion of people who received COVID-19 vaccine accounted for 79.56% (13 799/17 956), of which the highest proportion of three doses was 44.09%. The disease duration of 17 956 COVID-19 cases in the author's branch of makeshift hospital was 10.18 (7.34, 13.05) days. The disease duration in the elderly group was the longest with 11.34 (8.35, 14.37) days, followed by 11.17 (9.07, 14.33) days in the preschool group, 10.37 (8.14, 13.34)· days in the middle-aged group, 10.07 (7.37, 12.37) days in the school-age group, and 9.34 (7.05, 12.16) days in the young group. There was significant difference in the overall distribution of disease duration among the five groups (H=550.479 P<0.01). The disease duration in each age group basically showed a V-shaped distribution. The disease duration was 10.27 (7.34, 12.57) days in males and 10.10 (7.25, 13.09) days in females, and there was no significant difference (Z=-1.505 P>0.05). The disease duration of vaccinated patients was 10.24 (7.35, 13.05) days, and that of unvaccinated patients was 9.47 (7.09, 12.47) days. There was significant difference between the two groups (Z=-4.338 P<0.01). Conclusions COVID-19 Omicron variant cases have a high proportion of males, mainly young and middle-aged, and the proportion of fever patients is less than 30%. The disease duration is significantly lower than that of the original strain in Wuhan, and shows "V" distribution with each age group. Sex had no effect on the disease duration. COVID-19 vaccination did not have a clinical effect on the disease duration.

Objective:To evaluate the efficacy of 125I interstitial brachytherapy in the treatment of local advanced parotid adenoid cystic carcinoma (ACC), and to analyze prognostic factors affecting treatment outcome, in order to provide references for the treatment of local advanced parotid adenoid cystic carcinoma. Methods:Patients with histology-confirmed ACC of the parotid who received 125I interstitial brachytherapy in Peking University Hospital of Stomatology between Aug 2007 and Jan 2018 were included.Prognostic factors affecting overall survival (OS), progression-free survival (PFS), and local control rate (LCR) were analyzed.Meanwhile, distant metastases as well as acute and long-term radiological toxicities were described. Results:A total of 16 patients (11 females, mean age 55.4 years) of stage cT 4bN 0M 0 who received definitive 125I interstitial brachytherapy were included.The median follow-up period was 41.5 months (8-104 months), and the 1-, 3- and 5-year OS were 86.7%, 72% and 54%, respectively.Five patients suffered from local recurrence, the 1-, 3- and 5-year LCR were 93.7%, 80% and 68.7%, respectively, and the 1-, 3- and 5-year PFS were 74%, 53%, and 18.9%, respectively.Nine cases developed distant metastases.Among them, intracranial and pulmonary metastases took place the most frequently and six patients who had skull base invasion developed multi-organ metastases.An encased carotid artery was an independent prognostic factor for distant metastases (HR=12, P=0.045). Severe radiological toxicities were observed in eight patients (8/16, 50%), including radio-dermatitis, hearing loss, progressive trismus, and eye toxicities. Conclusions:The 5-year LCR in patients treated with definitive 125I interstitial brachytherapy for local advanced ACC of the parotid was 68.7%, and skull base invasion and an encased carotid artery were independent adverse prognostic factors of bad prognosis and multi-organ metastases.