The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Background Schizophrenia patients are often accompanied by negative symptoms and severe cognitive impairment,but effective interventions intended to alleviate such condition are currently limited.Existing researches on group play therapy for schizophrenia is still in its initial stages,and such therapy has the potential to contribute to symptoms improvement.Objective To explore the efficacy of group play therapy on improving cognitive function and negative symptoms in hospitalized female patients with schizophrenia,so as to provide references for clinical intervention in such group.Methods This study involved 40 female patients with schizophrenia who received inpatient treatment at the Third People's Hospital of Fuyang from April 2022 to May 2023 as well as met the diagnostic criteria of the International Classification of Diseases,tenth edition(ICD-10).They were divided into study group(n=20)and control group(n=20)according to the random number table method.Both groups received routine treatment,and the study group received 10 sessions of group play therapy for 5 weeks on the basis.At baseline,Scale for Assessment of Positive Symptoms(SAPS),Scale for Assessment of Negative Symptoms(SANS),Self-rating Depression Scale(SDS),Nurses' Observation Scale for Inpatient Evaluation(NOSIE),and Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)were used for assessment.Post-therapy evaluation was conducted by using SAPS,SANS and RBANS.Patients' baseline SAPS scores,SANS scores,RBANS total scores,and various factor scores of RBANS were used as covariates,and covariance analysis was adopted to compare the scores of each scale between the two groups after treatment.Results A total of 39 patients went through the whole study.Results of covariance analysis showed that the SANS score of study group was lower than that of control group,while several scores of RBANS(including total score,immediate memory factor score,speech function factor score and attention factor score)were all higher than those in control group.Significant difference was observed between two groups in scores of both scales above(F=13.408,10.331,4.932,9.967,10.010,P<0.05 or 0.01).Conclusion Group play therapy may help improve negative symptoms and cognitive function in hospitalized female patients with schizophrenia.

Objective To investigate the role and mechanism of exosomes derived from mesenchymal stem cells in hyperbaric oxygen caused pulmonary oxygen toxicity.Methods Mice were divided into the control group that was exposed to normal air,and hyperbaric oxygen exposure groups treated with phosphate buffer saline(PBS)or exosomes,respectively.PBS and exosome treatment were given one day prior to exposure.Mice were subjected to 0.23 MPa pure oxygen for 8 hours.The lung wet-dry ratio,inflammation,exudation and pathological injury were analyzed,while cell death and antioxidant related molecules were detected.Results Pretreatment with exosome significantly attenuated lung injury caused by hyperbaric oxygen exposure by decreasing the lung wet-dry ratio,inflammation,and cell apoptosis.Conclusion Prophylactic administration of exosomes derived from mesenchymal stem cells can alleviate hyperbaric oxygen induced pulmonary oxygen poisoning by attenuating cell death and inflammation.

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Objective To evaluate the clinical efficacy and safety of hyperthermic intraperitoneal chemotherapy(HIPEC)combined with systemic treatment in solid tumor with malignant ascites(MA).Methods The clinical data of 88 patients with MA who received HIPEC combined with systemic treatment in Department of Medical Oncology,Zhongshan Hospital,Fudan University from July 2020 to December 2022 were retrospectively analyzed.The control rate of MA was analyzed,and the clinicopathological characteristics of patients with effective and noneffective MA treatment were compared.The Kaplan-Meier method was used to analyze the MA control time of patients with gastric cancer and non-gastric cancer,and patients who used and did not use paclitaxel(PTX).The differences in peripheral blood immune cells before and after treatment were compared.Results Until May 31,2023,the overall control rate of HIPEC combined with systemic chemotherapy for MA was 72.73%(64/88),and the median control time was 5.82 months.There was no difference in serum albumin level,systemic treatment regimen and perfusion times etc.between the effective group and the noneffective group.There were differences in the short-term efficacy of MA among patients with different primary tumor,and the control rate of gastric cancer was higher than that of non-gastric cancer(82.69%vs 58.33%,P=0.023).Kaplan-Meier analysis showed that there was no difference in ascites control time between gastric cancer and non-gastric cancer patients(7.50 months vs 5.29 months,P=0.354);compared to non-PTX medicine such as 5-fluorouracil(5-FU)and cisplatin(DDP),PTX significantly prolonged the control time of ascites(6.44 months vs 2.73 months,P=0.024).After treatment,CD4+T/CD8+T rate elevated.48.86%(43/88)patients had mild abdominal distension and abdominal pain,which could be relieved in a short time after treatment;4.55%(4/88)patients discontinued anti-tumor treatment because of digestive adverse effects.Conclusions HIPEC combined with systemic chemotherapy is safe and effective for MA and has a better short-term efficacy for gastric cancer,and PTX as the perfusion agent for HIPEC can prolong the control time of MA.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Cell Differentiation ; Cells, Cultured ; Glucose ; Macrophages ; Periodontal Ligament ; Stem Cells

Cell Differentiation ; Nicotine/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Stem Cells

Objective:To investigate the correlation between three-dimensional histogram analysis of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and Gleason score(GS)in prostate cancer(Pca)from two hospital, and its diagnostic efficacy for discriminating low-grade from high-grade Pca.Methods:A total of 102 pathologically confirmed Pca patients in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Traditional Chinese Medical Hospital(TCM Hospital)Affiliated to Zhejiang Chinese Medical University from January 2017 to October 2020 were retrospectively analyzed.The quantitative parameters of Pca, including transport constant(K trans), rate constant(K ep), percent volume of the extravascular extracellular space(V e)and fraction of the Intraplasmic contrast volume(V p), were obtained by manually layer by layer delineating of interested regions of all lesions on the original DCE-MRI imaging.Then the three-dimensional histogram analysis of the above parameters were performed to obtain the minimum, maximum, median, mean, area, 10 thpercentile, 25 thpercentile, 75 thpercentile and 90 thpercentile.The correlations between quantitative parameters and GS, and diagnostic efficiencies were analyzed. Results:102 Pca patients were divided into low-grade prostate cancer group(GS≤3+ 4)(n=44)and high-grade Pca group(GS≥4+ 3)(n=58). There were no statistically significant differences in age and location of lesions between the two groups( P>0.05), but there were statistically significant differences in Gleason score, PSA level and lesion diameter between the two groups( U=0.000, 730.000, 711.000, all P<0.05). The median, mean, 10 thpercentile, 25 thpercentile, 75 thpercentile, 90 thpercentile derived from K trans, and K ep(median, mean, 10%, 25%, 75%, 90%)together with maximum of K transand mean for V e were positively correlated with GS( r=0.405 to 0.583, P<0.05), in which mean of K transhad the highest positive correlation( r=0.583, P=0.000). The histogram parameters derived from V pwere negatively correlated with GS( r=-0.301 to 0.341, P<0.05). The area under ROC of 75th percentile derived from K transwas the highest(0.832). When the cut-off value of 75 thpercentile derived from K transwas ≥0.680/min, its Youden index, sensitivity, and specificity were 0.594, 0.776, 0.818, respectively. Conclusions:The three-dimensional histogram of DCE-MRI quantitative parameters has correlation with GS in Pca patients, can be used to discriminate low-grade from high-grade Pca.