OBJECTIVE To investigate the effects of ertugliflozin on pharmacokinetic of sorafenib and donafenib in rats and explore the mechanism. METHODS Twenty-four male SD rats were randomly divided into four groups， with 6 rats in each group. Groups A and B were respectively gavaged with 0.5% sodium carboxymethyl cellulose solution and ertugliflozin （1.5 mg/kg） for 7 consecutive days， and both were given sorafenib （100 mg/kg） on the 7th day. Groups C and D were administered intragastrically in the same way as those in Groups A and B， respectively， for the first 7 days； after the drug administration on the 7th day， all rats in Groups C and D were further gavaged with donafenib （40 mg/kg）. Blood samples were collected at different time points before and after administration of sorafenib or donafenib， the concentrations of sorafenib in plasma of rats in groups A and B and donafenib in groups C and D were determined by UPLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Six additional rats were randomly divided into blank control group and ertugliflozin group， with three rats in each group. Blank control group was given 0.5% sodium carboxymethyl cellulose intragastrically， while rats in ertugliflozin group were given ertugliflozin （1.5 mg/kg） once a day for 7 consecutive days. After the last administration， the mRNA expression levels of uridine diphosphate glucuronosyl transferase 1A7 （UGT1A7）， breast cancer resistance protein （BCRP）， and P-glycoprotein （P-gp） in the liver and small intestine tissues of the rats were detected. RESULTS Compared with group A， the AUC0-t， AUC0-∞， cmax， tmax， MRT0-t and MRT0-∞ of sorafenib in group B were decreased significantly， while CL and V were increased significantly. Compared with group C， the AUC0-t， AUC0-∞ ， tmax， cmax and MRT0-t of Δ donafenib in group D were decreased significantly， while V and CL were increased significantly （P＜0.05）. mRNA expression of UGT1A7， P-gp and BCRP in the liver tissue and small intestine of rats were not significantly affected after intragastric administration of ertugliflozin for 7 consecutive days. CONCLUSIONS Ertugliflozin can affect the pharmacokinetics of sorafenib and donafenib in rats and decrease the plasma exposure of them significantly. However， its mechanism of action may not be through the regulation of related metabolic enzymes and transporters. When using drugs in combination clinically， one should be vigilant about the potential for disease progression due to poor therapeutic effects.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore the analgesic effect of different doses of dezocine combined with ropivacaine for thoracic paravertebral block(TPVB)on patients undergoing thoracoscopic radical resection of lung cancer and the influence on hemodynamics and immune function of patients.Methods Patients with lung cancer who underwent thoracoscopic radical resection were divided into low-dose group and high-dose group according to random number table method.Both groups of patients were given total intravenous anesthesia to complete the surgery.At 15 min before general anesthesia induction,the low-dose group was given TPBV with 0.1 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL,and the high-dose group was given TPBV with 0.15 mg·kg-1 dezocine+0.375％ropivacaine for a total of 20 mL.Comparisons were performed on both groups in terms of analgesic effect,hemodynamic parameters,immune function and occurrence of adverse drug reactions.Results There were 48 cases in low-dose group and 46 cases in high-dose group.In low-dose group,the heart rate values before TPVB,before skin incision,at 5 min after sectioning and at the end of surgery were(78.52±6.54),(70.79±7.07),(74.48±6.68)and(76.69±7.29)beat·min-1,the mean arterial pressure values were(93.16±5.72),(86.38±7.51),(92.15±6.36)and(91.14±6.13)mmHg.In high-dose group,the heart rate values at the above time points were(79.36±7.11),(71.68±6.49),(74.76±7.06)and(76.57±6.52)beat·min-1;the mean arterial pressure values were(93.89±7.18),(85.27±7.41),(90.34±6.52)and(92.43±6.34)mmHg,there were no statistical differences between the two groups(all P＞0.05).The resting state scores at 2,6 and 12 h after surgery were(1.38±0.19),(1.54±0.21)and(1.72±0.16)points,the pain scores at motion state were(1.88±0.15),(2.36±0.37)and(3.26±0.38)points in low-dose group;in high-dose group,the resting state scores were(1.32±0.17),(1.58±0.22)and(1.81±0.18)points,the pain scores at motion state were(1.81±0.13),(2.11±0.31)and(3.03±0.36)points,respectively,there were no statistical differences between the two groups(all P＞0.05).The number of analgesic pump compressions at 24 h after surgery and the number of cases with analgesic remedy were(5.12±1.26)times and 15 cases in low-dose group and were(4.74±1.03)times and 10 cases in high-dose group,with no statistical differences between the groups(all P＞0.05).The percentages of CD3+cells in low-dose group at the end of surgery and at 12 h and 24 h after surgery were(68.51±6.76)％,(54.22±5.43)％and(51.47±6.58)％,the percentages of CD4+cells were(40.29±5.02)％,(34.94±4.79)％and(30.48±5.11)％,CD4+/CD8+ratios were 1.54±0.34,1.36±0.28 and 1.16±0.23;the percentages of CD3+cells in high-dose group were(67.92±7.11)％,(56.58±6.36)％and(54.47±6.89)％,percentages of CD4+cells were(41.33±5.75)％,(35.86±5.21)％and(32.27±4.78)％,the CD4+/CD8+were 1.53±0.35,1.40±0.30 and 1.22±0.26,all with no significant difference(all P＞0.05).The incidence of postoperative adverse drug reactions in high-dose group and low-dose group were 32.61％and 14.58％,with significant difference(P＜0.05).Conclusion When TPVB regimen of dezocine combined with ropivacaine is used in thoracoscopic radical resection of lung cancer,the analgesic effect of low-dose dezocine is comparable to that of high-dose dezocine,with lower risk of adverse drug reactions.

Naturally derived metabolites are valuable resources for drug research and development, and play an important role in the treatment of diseases. As the "second genome" of the body, gut microbiota is rich in metabolic enzymes, which interacts with external substances such as drugs, thus affecting the progression of diseases. This article summarizes the interaction between gut microbiota-producing enzymes and natural medicines, and focuses on the impact of this interaction on disease progression, hoping to provide new ideas for the development and pharmacological mechanism of natural medicines.

Objective:To investigate the diagnostic value of serum homocysteine(Hcy),soluble stromelysin 2(sST2)and cystatin C(CysC)for chronic heart failure(CHF).Methods:A total of 86 CHF patients admitted in our hospital were se-lected as CHF group,and 86 healthy individuals who underwent physical examination simultaneously were selected as healthy control group.Serum levels of Hcy,sST2 and CysC,plasma level of N terminal pro brain natriuretic peptide(NT-proBNP)and cardiac function indexes[left atrial diameter(LAD),left ventricular end diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF)]were measured between two groups.Pearson correlation analysis was used to analyze the correlation among serum Hcy,sST2,CysC,plasma NT-proBNP and cardiac function indexes.Receiver operating characteristic curve(ROC)was drawn to evaluate the diagnostic value of serum Hcy,sST2 and CysC and their combined detection for CHF.Results:Compared with healthy control group,there were significant rise in scrum levels of Hcy,sST2 and CysC,plasma NT-proBNP level,LAD and LVEDd,and significant reduction in LVEF in CHF group,P=0.001 all.Pearson correlation analysis indicated that serum Hcy,sST2 and CysC levels were significant positively correlated with plas-ma NT-proBNP level,LAD and LVEDd(r=0.385～0.511,P＜0.05 or＜0.01),and significant inversely correlated with LVEF(r=-0.424～-0.402,P＜0.05 all).AUC of single detection of serum Hcy,sST2 and CysC diagnosing CHF was 0.624,0.720 and 0.870 respectively,and AUC of their combination was 0.865,which was significantly higher than any single detection,P＜0.05 or＜0.01.Conclusion:Serum levels of Hcy,sST2 and CysC abnormally increase in CHF patients,which can be used as auxiliary diagnostic indexes for CHF.The triple combined detection is of great signifi-cance for the diagnosis of CHF.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.