OBJECTIVE To evaluate the long-term toxicity of fully human anti-human tumor necrosis factor-α monoclonal antibody(anti-hTNF-α FHMA)for injection in cynomolgus monkeys. METHODS Forty cynomolgus monkeys were randomly divided into 5 groups (4 males and 4 females in each group):negative control group,adalimumab 10 mg·kg-1 group,anti-hTNF-αFHMA 2,10 and 50 mg·kg-1 groups. Cynomolgus monkeys in each group were injected sc once a week for 5 consecutive times, followed by 4 weeks of recovery. During the test,general clinical observation,body mass,body temperature,electrocardiogram(ECG),hematology,coagulation function,blood biochemistry,urine, ophthalmology,immune index,and pathological changes in organs and tissues were observed. At the same time,plasma drug concentrations were detected and the toxicokinetics parameters were analyzed. RESULTS No significant toxicological changes related to drugs were observed in general clinical observation,body mass,body temperature,ECG,ophthalmic examination,blood cell counts,coagu?lation function,blood biochemistry,urine analysis,lymphocyte subsets,cytokines,serum immuno?globulin,serum complement. Neutralizing anti-drug antibody(ADA)could be detected in adalimumab group and anti-hTNF-αFHMA groups. Anti-hTNF-αFHMA showed linear dynamic characteristics in cyno?molgus monkeys. At the same dose(10 mg·kg-1),anti-hTNF-αFHMA had similar immunogenicity and kinetics characteristics to adalimumab. CONCLUSION The level of anti-hTNF-α FHMA at which no adverse effect was observed was 50 mg · kg-1,which is equivalent to 75 times clinical dosage of quasi (0.67 mg·kg-1),which suggests that anti-hTNF-αFHMA be safe in clinical use.

Objective To explore the effects of aripiprazole on clinical symptoms and neurotrophic factor levels in patients with schizophrenia. Methods Forty patients with schizophrenia and 40 normal controls were included in the study. The clinical symptoms of patients receiving aripiprazole only for 12 weeks were evaluated by using the Positive and Negative Syndrome Scale (PANSS). Stroop Color-Word Test (SCWT), Continuous Performance Test, Digit-Symbol Coding Test and Trail Making Test-A were used to evaluate the cognitive function both in patients and controls. Serum levels of Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3) were measured using enzyme linked immunosorbent assay. Results The clinical scores, cognitive function and levels of neurotrophic factors were different before and after treatment (P<0.01). And those were significantly lower in patients than in control group (P<0.05). Before treatment, BDNF was negatively correlated with PANSS negative symptom score (r=-0.362, P=0.022);NGF was related to the total score of PANSS (r=0.332, P=0.037) and positive symptoms (r=0.401, P=0.010); NT-3 was associated with negative symptom scores (r=-0.376, P=0.017) and SCWT-color words (r=0.332, P=0.037) in patient group. After treatment, the increase in BDNF was correlated with the reduction in PANSS total score (r=0.371, P=0.018), negative symptom score (r=0.345, P=0.029) and general pathology score (r=0.342, P=0.031). There was a correlation of the increase of NGF with the decrease of PANSS total scores (r=0.437, P=0.005) and with positive symptom scores (r=0.357, P=0.024). Conclusion Treatment with Aripiprazole can improve the clinical symptoms and cognitive functiona impairments in patients with schizophrenia, which may be related to the increase in serum levels of BDNF, NGF and NT-3.

[Objective] To explore the effectiveness of applying the PDCA (Plan-Do-Check-Act) cycle to enhance the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients across multiple hospital campuses. [Methods] Clinical blood transfusion data from May to July 2022 were selected. Specific improvement measures were formulated based on the survey results, and the PDCA cycle management model was implemented from August 2022. The post-intervention phase spanned from August 2022 to October 2023. The Rh phenotype compatibility rate, the detection rate of Rh system antibodies, and the proportion of Rh system antibodies among unexpected antibodies were compared between the pre-intervention phase (May to July 2022) and the post-intervention phase. [Results] After the continuous improvement with the PDCA cycle, the compatibility rate for the five Rh blood group antigen phenotypes between donors and recipients from August to October 2023 reached 81.90%, significantly higher than the 70.54% recorded during the pre-intervention phase (May to July 2022, P<0.01), and displayed a quarterly upward trend (β=0.028, P<0.05). The detection rate of Rh blood group system antibodies (β=-9.839×10^-5, P<0.05) and its proportion among all detected antibodies (β=-0.022, P<0.05) showed a quarterly decreasing trend, both demonstrating a negative correlation with the enhanced compatibility rate (r values of -0.981 and -0.911, respectively; P<0.05). [Conclusion] The implementation of targeted measures through the PDCA cycle can effectively increase the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients, reduce the occurrence of unexpected Rh blood group antibodies, thereby lowering the risk of transfusion and enhancing the quality and safety of medical care.