Objective To evaluate the clinical efficacy of acupuncture combined with Modified Zuojin Granules in treating reflux esophagitis(RE)with liver-stomach disharmony syndrome.Methods A total of 100 patients diagnosed with liver-stomach disharmony syndrome RE were enrolled from October 2022 to October 2024 at Zigong First People's Hospital.The patients were randomly assigned to the observation group and the control group,with 50 cases in each group.The control group was treated with Modified Zuojin Granules,while the observation group was given acupuncture plus Modified Zuojin Granules,both group were treated for 4 weeks.The changes in the traditional Chinese medicine(TCM)syndrome scores,24-hour esophageal acid reflux parameters(frequency and longest duration),serum gastrointestinal hormones[gastrin(GAS),motilin(MTL),vasoactive intestinal peptide(VIP)],gut microbiota composition(Lactobacillus,Bifidobacterium,Enterococcus,Enterobacter)were observed.The adverse reactions and safety profiles were evaluated.Results(1)Both groups showed significant improvement in TCM syndrome scores(P＜0.05),with greater improvement in the observation group,and the differences were statistically significant(P＜0.05).(2)After treatment,both groups of patients showed significant improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration(P＜0.05).The observation group demonstrated significantly better improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration compared to the control group,with statistically significant differences(P＜0.05).(3)After treatment,the serum levels of GAS,MTL,and VIP in both groups of patients were significantly improved(P＜0.05).The observation group showed significantly better improvement in serum GAS,MTL,and VIP levels compared to the control group,with statistically significant differences(P＜0.05).(4)After treatment,the levels of Lactobacilli and Bifidobacteria in both groups increased significantly compared to before treatment(P＜0.05),while the levels of Enterococci and Enterobacteria were significantly decreased(P＜0.05).The improvement in intestinal microbiota levels was more pronounced in the observation group,with statistically significant differences(P＜0.05).(5)The overall efficacy rate was 96.00％(48/50)in the observation group and 80.00％(40/50)in the control group.The observation group demonstrated superior efficacy compared to the control group,with statistically significant differences(P＜0.05).(6)The incidence of adverse reactions in the observation group was 8.00％(4/50),while that in the control group was 12.00％(6/50).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The combined therapy significantly improves clinical symptoms,modulates gastrointestinal hormones and gut microbiota,demonstrating excellent efficacy and safety for liver-stomach disharmony syndrome RE.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective To explore the intrinsic connectivity alterations of brain-wide functional networks in patient with trigeminal neuralgia(TN)via combining resting-state functional magnetic resonance imaging(rs-fMRI)and graph theory methods.Methods A total of 41 patients with TN(TN group)and 41 healthy controls(HC)(HC group)were recruited,and differences in network topologyat-tributes and correlations with clinical variables were analyzed between the two groups.Results Both groups met the σ standard.The global efficiency(Eg)of TN group was lower than that of HC group(P＜0.05),whereas the λ of TN group was higher than that of HC group(P＜0.05).The node efficiency(Ne)of bilateral rectus gyrus and bilateral pallidum of TN group were significantly higher than those of HC group,while the Ne of left supraparietal gyrus,left angular gyrus,left post-central gyrus,bilateral marginal supraparietal gyrus,and left caudate nucleus of TN group were significantly lower than those of HC group(P＜0.05).The local efficiency(Eloc)of the TN group was negatively correlated with the visual analogue scale(VAS)score(P＜0.05),the clustering coefficient(Cp)of the TN group was negatively correlated with the short-form McGill pain questionnaire(SF-MPQ)sensory score(P＜0.05),and the Ne of right rectus gyrus of the TN group was positively correlated with the disease duration(P＜0.05).Conclusion The TN group retain σ,but the overall information transfer efficiency of the brain is reduced and functional integration is diminished.Several brain regions in the TN group has abnormal Ne,which provide an objective basis for altered brain functional networks in TN.