ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

Objective To sort out the management system of clinical trial drugs in our hospital,and analyze the construction and practical experience of the information system in the whole process management of clinical trial drugs,and to further improve the efficiency and quality of clinical trials.Methods Based on the original management of clinical trial drugs,an information system in line with the situation of our hospital was applied to manage the whole process of clinical trial drugs.Results Compared with the traditional management,the information system can automatically record the data of inbound and outbound storage,distribution,retrieval and return of trial drugs in real time,pre-review the prescriptions and randomized documents of clinical trial drugs,and realise paperless office.Conclusions The information system can ensure the safety,accuracy and traceability of the data of drugs used in clinical trial.The system can also save resources,improve the efficiency and quality of clinical trial management.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective To sort out the management system of clinical trial drugs in our hospital,and analyze the construction and practical experience of the information system in the whole process management of clinical trial drugs,and to further improve the efficiency and quality of clinical trials.Methods Based on the original management of clinical trial drugs,an information system in line with the situation of our hospital was applied to manage the whole process of clinical trial drugs.Results Compared with the traditional management,the information system can automatically record the data of inbound and outbound storage,distribution,retrieval and return of trial drugs in real time,pre-review the prescriptions and randomized documents of clinical trial drugs,and realise paperless office.Conclusions The information system can ensure the safety,accuracy and traceability of the data of drugs used in clinical trial.The system can also save resources,improve the efficiency and quality of clinical trial management.

Objective:To evaluate the efficacy and safety of anaprazole (40 mg and 60 mg) and compared with rabeprazole (20 mg) in the treatment of reflux esophagitis (RE).Methods:This multicenter, randomized, double-blinded, positive drug parallel controlled study was led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) and a total of 24 clinical trial institutions nationwide including the First Affiliated Hospital of Nanchang University, Yichun People′s Hospital, Meihekou Central Hospital, the First Affiliated Hospital of Gannan Medical University, and Jinhua Central Hospital, participated in this research. A total of 156 patients with RE (Los Angeles grade A to D) were enrolled and randomly divided into 3 groups, anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group, using a random number table in a ratio of 1∶1∶1. Patients in the above 3 groups were treated with the appropriate trial medication once per day for 4 or 8 weeks. The endoscopic healing rates were evaluated by Blinded Independent Central Review (BICR) and investigators. In addition, the improvement in the severity of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) and medication safety were also evaluated. The endoscopic healing rates and 95% confidence intervals (95% CI) at week-8 and -4 were calculated by groups, as well as the difference in the healing rates and their 95% CI among groups. The chi-square test was used for statistical analysis. Results:A total of 153 subjects were included in the full analysis set (FAS), 144 in the per-protocol analysis set (PPS) and 151 in the safety set (SS). In the FAS, after 8 weeks of treatment, the endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly assessed by BICR were 86.0% (43/50), 86.5% (45/52) and 86.3% (44/51), respectively, and the 95% CI were 76.4% to 95.6%, 77.3% to 95.8% and 76.8% to 95.7%, respectively.The endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly evaluated by investigators were 88.0% (44/50), 90.4% (47/52) and 86.3% (44/51), respectively, and the 95% CI were 79.0% to 97.0%, 82.4% to 98.4% and 76.8% to 95.7%, respectively. The endoscopic healing rates were similar among groups. In the FAS, the differences in healing rates(95% CI) assessed by BICR and investigators between anaprazole 40 mg, anaprazole 60 mg and rabeprazole 20 mg group were -0.3%(-13.7% to 13.2%), 0.6%(-12.3% to 13.6%), respectively and 1.7%(-11.3% to 14.8%), 3.9%(-8.5% to 16.3%), respectively. The results of the PPS were consistent with those of the FAS. After 8 weeks of treatment, the severity scores of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) decreased in all groups. The differences between post-treatment and baseline in anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were -1.54±1.00, -1.91±1.00, -1.51±0.76, -1.45±0.71; -1.30±0.94, -1.59±0.96, -1.33±0.65, -1.42±0.60; and -1.74±0.85, -1.76±0.93, -1.45±0.66, -1.66±0.79, respectively. The incidence of treatment emergent adverse event of anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were 57.1% (28/49), 48.1% (25/52) and 60.0% (30/50), respectively, and the incidence of treatment related adverse event were 18.4% (9/24), 25.0% (13/52) and 24.0% (12/50), respectively. There were no statistically significant differences in the incidence of treatment emergent adverse event and treatment related adverse event among 3 groups (all P>0.05). Conclusion:The efficacy and safety of anaprazole 40, 60 mg/d, and rabeprazole 20 mg/d in the treatment of RE are comparable.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching.The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P＜0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P＜0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P＞0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P＜0.05).After 1-2 months of immuno-suppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P＞0.05),but there was an improvement in the 2PN embryo cleavage rate(P＜0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P＜0.05),with no significant differences in the miscarriage rate between the two groups(P＞0.05).Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.

Objective:To evaluate the efficacy and safety of anaprazole (40 mg and 60 mg) and compared with rabeprazole (20 mg) in the treatment of reflux esophagitis (RE).Methods:This multicenter, randomized, double-blinded, positive drug parallel controlled study was led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) and a total of 24 clinical trial institutions nationwide including the First Affiliated Hospital of Nanchang University, Yichun People′s Hospital, Meihekou Central Hospital, the First Affiliated Hospital of Gannan Medical University, and Jinhua Central Hospital, participated in this research. A total of 156 patients with RE (Los Angeles grade A to D) were enrolled and randomly divided into 3 groups, anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group, using a random number table in a ratio of 1∶1∶1. Patients in the above 3 groups were treated with the appropriate trial medication once per day for 4 or 8 weeks. The endoscopic healing rates were evaluated by Blinded Independent Central Review (BICR) and investigators. In addition, the improvement in the severity of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) and medication safety were also evaluated. The endoscopic healing rates and 95% confidence intervals (95% CI) at week-8 and -4 were calculated by groups, as well as the difference in the healing rates and their 95% CI among groups. The chi-square test was used for statistical analysis. Results:A total of 153 subjects were included in the full analysis set (FAS), 144 in the per-protocol analysis set (PPS) and 151 in the safety set (SS). In the FAS, after 8 weeks of treatment, the endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly assessed by BICR were 86.0% (43/50), 86.5% (45/52) and 86.3% (44/51), respectively, and the 95% CI were 76.4% to 95.6%, 77.3% to 95.8% and 76.8% to 95.7%, respectively.The endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly evaluated by investigators were 88.0% (44/50), 90.4% (47/52) and 86.3% (44/51), respectively, and the 95% CI were 79.0% to 97.0%, 82.4% to 98.4% and 76.8% to 95.7%, respectively. The endoscopic healing rates were similar among groups. In the FAS, the differences in healing rates(95% CI) assessed by BICR and investigators between anaprazole 40 mg, anaprazole 60 mg and rabeprazole 20 mg group were -0.3%(-13.7% to 13.2%), 0.6%(-12.3% to 13.6%), respectively and 1.7%(-11.3% to 14.8%), 3.9%(-8.5% to 16.3%), respectively. The results of the PPS were consistent with those of the FAS. After 8 weeks of treatment, the severity scores of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) decreased in all groups. The differences between post-treatment and baseline in anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were -1.54±1.00, -1.91±1.00, -1.51±0.76, -1.45±0.71; -1.30±0.94, -1.59±0.96, -1.33±0.65, -1.42±0.60; and -1.74±0.85, -1.76±0.93, -1.45±0.66, -1.66±0.79, respectively. The incidence of treatment emergent adverse event of anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were 57.1% (28/49), 48.1% (25/52) and 60.0% (30/50), respectively, and the incidence of treatment related adverse event were 18.4% (9/24), 25.0% (13/52) and 24.0% (12/50), respectively. There were no statistically significant differences in the incidence of treatment emergent adverse event and treatment related adverse event among 3 groups (all P>0.05). Conclusion:The efficacy and safety of anaprazole 40, 60 mg/d, and rabeprazole 20 mg/d in the treatment of RE are comparable.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ