Adverse drug reactions （ADRs） refer to harmful or unintended reactions unrelated to the intended purpose of medication administration， which can lead to various issues such as accelerated disease progression and prolonged hospitalization. Traditional ADRs monitoring systems （such as spontaneous reporting systems） suffer from limitations such as low reporting rates and inconsistent data quality， which hinder the early prevention and control of ADRs. With the rapid development of information technology， machine learning has emerged as a powerful tool for management and decision-making of ADRs by leveraging its strengths in feature extraction and dynamic temporal pattern analysis. By reviewing relevant literature at home and abroad in recent years， this paper summarizes the progress in the application of machine learning for ADRs prediction. It is found that machine learning has gradually been applied to the early warning and risk prediction of ADRs in target organs such as the kidneys， liver， heart and bone marrow （such as acute kidney injury， drug-induced liver injury， and so on）. Although machine learning demonstrates significant application potential in the field of ADRs prediction， it still faces limitations such as inadequate quality control of clinical data， lack of standardized criteria for model performance evaluation， insufficient model interpretability and difficulties in clinical translation. In the future， the development trend of machine learning in the field of ADRs prediction should follow a “technology-validation-integration” pathway to systematically promote the practical implementation of models.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Excavating the quantitative trait locus (QTL) associated with rice cooking quality, analyzing candidate genes, and improving cooking quality-associated traits of rice varieties by genetic breeding can effectively improve the taste of rice. In this study, we used the indica rice HZ, the japonica rice Nekken2 and 120 recombinant inbred lines (RILs) populations constructed from them as experimental materials to measure the gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) of rice at the maturity stage. We combined the high-density genetic map for QTL mapping. A total of 26 QTLs associated with rice cooking quality (1 QTL associated with GT, 13 QTLs associated with GC, and 12 QTLs associated with AC) were detected, among which the highest likelihood of odd (LOD) value reached 30.24. The expression levels of candidate genes in the localization interval were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and it was found that the expression levels of six genes were significantly different from that in parents. It was speculated that the high expression of LOC_Os04g20270 and LOC_Os11g40100 may greatly increase the GC of rice, while the high expression of LOC_Os01g04920 and LOC_Os02g17500 and the low expression of LOC_Os03g02650 and LOC_Os05g25840 may reduce the AC. The results lay a molecular foundation for the cultivation of new high-quality rice varieties, and provide important genetic resources for revealing the molecular regulation mechanism of rice cooking quality.
Quantitative Trait Loci ; Oryza/genetics* ; Plant Breeding ; Cooking ; Genetic Association Studies

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Malnutrition is highly prevalent in patients with inflammatory bowel disease, which can be life-threatening when refeeding syndrome occurs. This article reports a patient with Crohn′s disease admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine who developed refeeding syndrome due to long-term malnutrition and complicating lymph node tuberculosis. After the discussion, diagnosis and treatment of multidisciplinary team including Departments of Gastroenterology, Nutrition, Colorectal Surgery and Oncology, and Pathology, the patient was improved significantly.

Malnutrition is highly prevalent in patients with inflammatory bowel disease, which can be life-threatening when refeeding syndrome occurs. This article reports a patient with Crohn′s disease admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine who developed refeeding syndrome due to long-term malnutrition and complicating lymph node tuberculosis. After the discussion, diagnosis and treatment of multidisciplinary team including Departments of Gastroenterology, Nutrition, Colorectal Surgery and Oncology, and Pathology, the patient was improved significantly.

Objective: To analyze the causes of death in Keqiao District, Shaoxing City in 2020, so as to provide the evidence for formulating the disease control strategy. Methods: The dead cases' gender, age and causes of death in Keqiao District, 2020, were collected from Shaoxing Municipal Public Health Information System, and the mortality was estimated and standardized by the 2020 Chinese standard population. The gender- and age-specific mortality and distribution of causes of death were analyzed, and the years of potential life lost (YPLL), average years of potential life lost per death (AYLL) and YPLL rate (YPLLR) were calculated to evaluate the life lost. Results: The crude and standardized mortality rates of registered residents in Keqiao District were 636.97/105 and 494.72/105, respectively. The crude and standardized mortality rates were 712.67/105 and 512.23/105 in men and 564.75/105 and 473.25/105 in women, and a higher mortality rate was seen in men than in women (χ2=59.628, P<0.001). The mortality reduced and then increased with age, and peaked among residents at ages of 85 years and older (13 910.90/105). Chronic disease was the main cause of death, accounting for 85.60% of all causes of death and showing a mortality rate of 545.27/105. Cancer, cardiopathy, cerebrovascular disease, injury and poisoning, and respiratory diseases were the five leading causes of death, and lung cancer, gastric cancer, colorectal cancer, liver cancer and pancreatic cancer were the five leading causes of cancer-related mortality. The highest YPLL was caused by cancers (13 015.00 person-years), with a YPLLR of 1.88%, and the highest AYLL was caused by injury and poisoning (10.37 years). Conclusion Chronic non-communicable diseases, such as cancer and cardio-cerebrovascular diseases, were main causes of death among residents in Keqiao District in 2020. The management of chronic diseases requires to be reinforced to improve the quality of life.

Objective:To describe for the determination of contents of metabolites of benzene compounds in urine sample by high performance liquid chromatography.Methods:After acidification with hydrochloric acid, metabolites in urine were first extracted by acetonitrile and isopropanol (V∶V, 9∶1) with excessive sodium chloride, then gradient separated on a C18 column and then determined by DAD detector.Results:There were good linear relationship between peak areas and injection quality in range of 2.00-100 mg/L ( r>0.999). The detection limit and quantitative limit of this method were 4.15-70.7 μg/L and 13.8-235 μg/L respectively. The precision for the analysis of urine was1.78%-8.23% ( n =6). The average recovery of metabolites was 85.4%-105.5% at thee spiked levels in the range of 2.00-100 mg/L. Conclusion:The accuracy and reproducibility obtained make this method useful for the biological monitoring of occupational exposure to toluene, xylene, styrene and ethylbenzene.

Objective:To analyze the direct economic burden of occupational asthma patients and provide economic basis for the government to rationally allocate health resources.Methods:In September 2019, colleted the case data of 53 patients diagnosed with occupational asthma who were hospitalized in our hospital from December 2008 to December 2018, and analyze the impact of gender, age, diagnosis time, ducation level, allergen type to the length of stay, hospitalization cost, medical technology diagnosis and treatment costs, western medicine costs, average daily hospitalization costs and other indicators.Results:The average length of hospitalization for occupational asthma patients was (38.7±8.1) days, and the average hospitalization cost was 14743 yuan, of which medical technology diagnosis and treatment costs, western medicine costs, and comprehensive medical service costs accounted for the top three, 42.5% (331977/781369) , 32.0% (249942/781369) , 19.6% (153268/781369) respectively. Hospitalization days for occupational asthma patients has decreased significantly in 2014-2018 ( P<0.05) . There were no significant differences in hospitalization costs, medical technology diagnosis and treatment costs, western medicine costs, and average daily hospitalization costs for occupational asthma patients caused by different allergens (isocyanates, persulfates and phthalic anhydrides) ( P>0.05) . Hospitalization days, hospitalization costs, medical technology diagnosis and treatment costs, western medicine costs, and average daily hospitalization costs of patients with moderate occupational asthma were significantly higher than those of mild patients ( P<0.05) . Conclusion:Early detection of occupational asthma patients and early intervention can reduce the economic burden on patients and society.