Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P＞0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.

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 To construct and apply a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.Methods Based on evidence summaries and expert consultation,a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients was constructed,consisting of 19 items covering 7 aspects including identification of risk factors,position management,tube and cuff selection,cuff management,mechanical ventilation management,pain and sedation management,removal of oropharyngeal and subglottic secretions,and oral care.Convenience sampling was used to select 141 ICU intubated patients from a tertiary A comprehensive hospital in Suzhou from June,2022 to September,2023.Patients were divided into an experimental group(n=72)and a control group(n=69)according to the wards.The experimental group received the management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.The control group received the nursing bundle for ventilator associated pneumonia(VAP).The incidence and time from intubation to microaspiration and VAP,duration of mechanical ventilation,ICU length of stay,and disease outcome were compared between the 2 groups.Results The incidence of microaspiration of oropharyngeal secretions,the duration of mechanical ventilation,time from intubation to microaspiration showed significant differences between the 2 groups(P<0.05).There were no significant differences in the incidence of ventilator associated pneumonia,ICU length of stay,and disease outcome between the 2 groups(P>0.05).The time from intubation to VAP in the experimental group was 7.5 days,and that in the control group was 3.8 days.Conclusion The application of the management plan for microaspiration of orophaiyngeal secretions in ICU intubated patients is beneficial for reducing the incidence of microaspiration,delaying the time from intubation to microaspiration and VAP,and shortening the duration of mechanical ventilation.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC₅₀), IC₅₀, 2×IC₅₀, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC₅₀), 20 (IC₅₀) and 40 (2×IC₅₀) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe²⁺, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
Ferroptosis/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Breast Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Female ; Cell Line, Tumor ; Tumor Suppressor Protein p53/metabolism* ; Amino Acid Transport System y+/metabolism* ; Humans ; Reactive Oxygen Species/metabolism* ; Animals ; Mice ; Cell Proliferation/drug effects* ; Mitochondria/metabolism* ; Coenzyme A Ligases/metabolism* ; Cell Movement/drug effects* ; Benzopyrans

Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O