Objective To identify the metabolites of loganin in rat urine through using ultra high performance liquid chromatography combined with triple TOF mass spectrometry (UPLC-Q-TOF/MS/MS) after oral administration of loganin;To summarize the metabolic pathway of loganin. Methods Rats were given a gavage with loganin. The urine samples were prepared by use of solid phase extraction (SPE). The chromatographic separation was performed on an UPLC C18 column with gradient elution program of acetonitrile and 0.1% formic acid aqueous as mobile phase. Dynamic background subtraction (DBS) technology was employed to trigger information dependent acquisition (IDA) to obtain the characteristic fragment ions of metabolites. Results MetabolitePilot software including several data processing methods were employed to speculate the structures of liganin metabolites and three metabolites were identified. Then, the metabolic pathway of loganin in rats was summarized. Conclusion The analytical method was simple, credible and highly-sensible, which is useful for screening and identifying trace constituents in vivo.

Objective To analyze the characteristics and influencing factors of sleep disorders and nocturnal hypoxemia of patients with different degrees of obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Four hundred and twenty-five patients with snoring were scored by Epworth Sleepiness Scale ( ESS), and monitored by polysomnography (PSG). The possible correlations between sleep structure, hypoxia parameters, ESS and clinical features were analyzed and compared in those patients. Results Four hundred and twenty-five patients were divided into 4 groups according to the apnea-hypopnea index (AHI). There were 65 primary snoring patients (15.3%) and 360 OSAHS patients (84. 7% ) including 187 patients (44. 0% ) in severe OSAHS group. ESS was increased as aggravation of OSAHS. There were significant statistical differences in ESS among each group. Compared with primary snoring group, sleep efficiency, NREM1 + 2, oxygen desaturation index ( ODI), time with pulse oxygen saturation below 90% (T(SpO2 <90% ) ) were significantly higher in the OSAHS groups, and NREM3 +4, lowest pulse oxygen saturation level ( LSpO2 ) were lower. ESS was correlated positively with AHI (r= 0. 474,P <0. 01 ). They were both correlated positively with ODI, T (SpO2 <90% ) and NREM1 + 2( ESSr =0. 392, 0. 356,0. 194;AHI r = 0. 714, O. 682, 0. 365, all P < 0. 01 ), and correlated negatively with LSpO2, NREM3 + 4 ( ESS r = - 0. 414, - 0. 196; AHI r = - 0. 740, - 0. 385, both P < 0. 01 ). LSpO2, ODI and T (SpO2 < 90% ) were the primary influencing factors. Common clinical presentations and subjective symptoms were presented including daytime sleepiness, impaired memory, fatigue, dry mouth, oppressive wake and morning headache, etc. Percentage of individuals with daytime sleepiness in the severe OSAHS group was 73. 3% (137/187). These had serious impact on the patients' quality of life, leading to difficulty concentrating, poor memory and cognitive impairment. Conclusions Sleep disorders are found in the patients with different degrees of OSAHS. The excessive daytime sleepiness interrelated partly with the structure of sleep, and totally with hypoxia parameters. The more severity the patients have, the more nocturnal hypoxia, sleep disorders and higher ESS are found.

Objective To investigate the characteristics of the objective sleep disturbances in Parkinson' s disease (PD) and the factors related to it.Methods One hundred and one PD patients and 90 age- and sex- matched controls underwent a video-polysomnography.The sleep parameters and its related factors in two groups were analyzed.Results Sleep latency was not statistically different in comparing two groups.PD patients had a higher percentage of non-rapid eye movement( non-REM ) sleep stage 1 and a lower percentage of non-REM sleep stage 2 compared with controls ( 27.9 ± 1 7.8 vs 21.2 ± 11.7,t =3.034,P =0.003 ;47.8 ± 17.4 vs 54.7 + 12.9,t =- 3.043,P =0.003 ).Reduced sleep efficiency,decreased the proportion of slow wave sleep and REM sleep,increased awake time and longer REM sleep latency occurred in PD patients.There were no significant differences of these above parameters.Some sleep parameters in PD patients were correlated with advancing age,the severity of PD,and the degree of depression.The index of periodic leg movements in sleep (PLMSI) of 41 PD patients (40.6％ ) was more than 15.These PD patients didn' t complain corresponding symptoms about their legs.The PLMSI in PD patients were significantly higher than the controls.PLMSI increased with aging in the PD group( r =0.261,P ＜0.01 ).PD patients didn' t suffer significantly lower apnea- hypopnea index and oxygen desaturation index.The lowest SPO2 ( L-SPO2 ) increased in the PD group.REM sleep without atonia occurred in 83 patients (82.2％) with PD.Thirty-eight patients (37.6％) were diagnosed with REM sleep behavior disorder (RBD).The incidences of REM without atonia and RBD in the PD group were significantly higher than in the control s(0 and 8 patients (8.9％),x2 =42.271,102.480; both P ＜ 0.01 ).Conclusions The sleep parameters in PD patients are changed.For PD patients,there is no difficulty in falling asleep.The PD patients also have sleep structure disorder and difficulty in maintaining sleep.The sleep parameters are correlated with advancing age,the severity of PD,and the degree of depression in PD.PLMS don' t lead to sleep disturbances in PD patients.The blood oxygen saturation don' t decrease severely when PD patients suffer apnea or hypopnea.RBD occur more frequently in PD patients.

Objective:To construct a perioperative activity program for patients with minimally invasive esophageal cancer under enhanced recovery after surgery (ERAS) concept through literature review and Delphi method.Methods:This was a single-center and interview study. Databases and websites including PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Medive and other databases and websites were searched systematically for articles related to esophageal cancer and upper digestive tract cancer patients′ activities from January 1, 2002 to January 31, 2022. In this single-center and interview study, literature review and group discussion were conducted to form a preliminary activity program, and then Delphi method was used to further demonstrate the practicability and feasibility of the activity program.Results:The overall program and specific intervention methods of perioperative activity program for minimally invasive esophageal cancer patients under ERAS concept were constructed, including 3 first-level indicators, 9 second-level indicators and 35 third-level indicators.Conclusions:Perioperative activity program of patients with minimally invasive esophageal cancer is scientific and reasonable, which can provide reference for medical staff and patients.

OBJECTIVETo develop and validate a HPLC-UV-ELSD method for the simultaneous determination of ginsenosides and epimedium flavonoids in rat urine after intravenous administration of Jiweiling freeze-dried powder.

METHODChromatographic separation was performed on a C18 HPLC column, with gradient elution of acetonitrile and water as mobile phase. An UV detector was used at detection wavelength of 220 nm. An evaporative light scattering detector (ELSD) was used at drift tube temperature of 80 degrees C and gas pressure of 172.4 kPa.

RESULTThe calibration curves were linear over the investigated concentration ranges with all correlation coefficients higher than 0.998. The a intra- and inter-day RSD were less than 9.1% and the relative errors were verage extraction recoveries for all compounds were between 88.67% and 101.2%. The within the range of -11.58% to 10.89%.

CONCLUSIONThe proposed method showed appropriate accuracy and selectivity and was successfully applied to the rat urine samples analysis of saponins and flavonoids after intravenous administration of Jiweiling freeze-dried powder, which may provide some references to the apprehension of the action mechanism and clinical application.

Animals ; Calibration ; Chromatography, High Pressure Liquid ; methods ; Epimedium ; chemistry ; metabolism ; Flavonoids ; urine ; Ginsenosides ; urine ; Phytotherapy ; Plant Preparations ; Rats ; Saponins ; analysis ; Ultraviolet Rays

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.

OBJECTIVE To explore the improvement effect and potential mechanism of Baicao fuyanqing suppository on bacterial vaginitis （BV） in rats. METHODS The female SD rats were randomly divided into normal group， model group， metronidazole group （positive control， 0.03 g/kg）， Baicao fuyanqing suppository low-dose， medium-dose and high-dose groups （0.18， 0.36， 0.72 g/kg）， with 8 rats in each group. Except for the normal group， the rats in other groups were injected subcutaneously with 0.2 g of Estradiol benzoate injection+20 μL of Escherichia coli suspension （2×108～3×108 cfu/mL） through the vaginal opening to establish the BV rat model. Administration groups were given relevant medicine vaginally， while the normal group and the model group were given normal saline， once a day， for 6 consecutive days. Twenty-four hours after the last administration， the vaginal appearance score and vaginal pH were measured for each group of rats. The levels of cytokines [interleukin-1β （IL-1β）， IL-2， IL-13， immunoglobulin A （IgA）] in vaginal lavage fluid were determined. The morphology of the uterus and accessories， and pathological changes in the vaginal tissue were observed. The expressions of Toll-like receptor 2 （TLR2）， TLR4 and nuclear factor-κB （NF-κB） in vaginal tissues were determined. RESULTS Compared with the normal group， the uterus edema， the irregular shape of uterus and accessories， the vaginal mucosa hyperplasia， and the massive desquamation of epithelial cells were observed in the model group， complicating with massive infiltration of inflammatory cells； vaginal opening redness and swelling score and secretion score， vaginal pH， the levels of proinflammatory cytokine IL-1β and IL-2， the protein expressions of TLR2， TLR4 and NF- κB were all increased or up-regulated， while the levels of IgA and anti-inflammatory cytokine IL-13 decreased significantly （P＜0.05 or P＜0.01）. Compared with the model group， varying cn degrees of improvement in uterine and accessories， and vaginal tissue lesions in rats were observed in administration groups， and most of the quantitative indicators mentioned above showed significant improvement （P＜0.05 or P＜0.01）. CONCLUSIONS Baicao fuyanqing suppository has a certain improvement effect on inflammatory symptoms in BV rats， and its mechanism may be related to the inhibition of the TLR/NF-κB signaling pathway.