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.

ObjectiveTo establish a highly specific and sensitive triplex TaqMan quantitative PCR method for the detection of mouse hepatitis virus (MHV), mouse parvovirus (MPV), and reovirus type 3 (Reo-3) in laboratory mice. MethodsRecombinant plasmid standards were constructed using conserved genomic regions of the three target viruses. Specific primers and probes were designed, and a triplex TaqMan quantitative PCR (qPCR) system was optimized through preliminary experiments. Sensitivity was evaluated using 10-fold serial dilutions (10¹-10⁷ copies/μL). Intra- and inter-assay repeatability were assessed via reproducibility experiments. ResultsA strong linear correlation (R ²>0.99) was observed between copy number and Ct value at template concentrations of 10²-10⁷ copies/μL. Intra-assay and inter-assay coefficients of variation (CV) were both below 5%. No cross-reactivity was observed with mouse cytomegalovirus (MCMV), vesicular stomatitis virus (VSV), Sendai virus (SeV), or pneumonia virus of mice (PVM). ConclusionThe triplex TaqMan quantitative PCR method established in this study has high sensitivity, good repeatability, and strong specificity. It enables the rapid, specific, and sensitive detection of MHV, MPV, and Reo-3, allows the simultaneous detection of multiple pathogens in a single tube, and can be applied to the detection of clinical samples from laboratory animals and to epidemiological investigations, thereby providing effective scientific and technological support for the prevention and control of viral infection and the interruption of transmission.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:To construct an evaluation indicator system for power system of otolaryngology surgery,so as to provide references for the configuration of surgical power devices of medical institutions.Methods:Literature review and brainstorming were used to analyze existing literature related to surgical power.Combined with expert opinions and clinical demands,an evaluation indicator system was initially proposed.The Delphi method was adopted to determine the evaluation indicators of power system of otolaryngology surgery.The analytic hierarchy process(AHP)method was used to determine the evaluation indicator system of the power system of otolaryngology surgery,which were constructed by weight of each indicator.Results:The evaluation indicator system of power system of otolaryngology surgery included 5 first-level indicators(integrity of medical equipment,products'performance indicators,safety,clinical application effect,and after-sales service guarantee)and 49 second-level indicators under the first-level indicators.In the first-level indicators,equipment's safety had the highest weight(20.48%).In the second-level indicators,the top three of the combined weights were respectively integrity of equipment's main device(7.19%),accessory's integrity(7.03%),and identification's integrity(6.03%).Conclusion:The evaluation index system for otolaryngological surgical power systems clarifies the core dimensions,specific indicators and relative importance of the evaluation,and can be applied to the procurement and selection of surgical power devices in medical institutions,performance testing,clinical effect evaluation and other aspects.

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

Objective:To construct an evaluation indicator system for power system of otolaryngology surgery,so as to provide references for the configuration of surgical power devices of medical institutions.Methods:Literature review and brainstorming were used to analyze existing literature related to surgical power.Combined with expert opinions and clinical demands,an evaluation indicator system was initially proposed.The Delphi method was adopted to determine the evaluation indicators of power system of otolaryngology surgery.The analytic hierarchy process(AHP)method was used to determine the evaluation indicator system of the power system of otolaryngology surgery,which were constructed by weight of each indicator.Results:The evaluation indicator system of power system of otolaryngology surgery included 5 first-level indicators(integrity of medical equipment,products'performance indicators,safety,clinical application effect,and after-sales service guarantee)and 49 second-level indicators under the first-level indicators.In the first-level indicators,equipment's safety had the highest weight(20.48%).In the second-level indicators,the top three of the combined weights were respectively integrity of equipment's main device(7.19%),accessory's integrity(7.03%),and identification's integrity(6.03%).Conclusion:The evaluation index system for otolaryngological surgical power systems clarifies the core dimensions,specific indicators and relative importance of the evaluation,and can be applied to the procurement and selection of surgical power devices in medical institutions,performance testing,clinical effect evaluation and other aspects.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective To compare the consistency between the estimated values of nine common resting energy expenditure estimation equations and the measured values among the elderly population in pension institutions. Methods A total of 181 elderly individuals from Henan Guangda Ouan Leling Nursing Center were recruited as study objects through cluster sampling. The differences between the estimated values of nine common equations and the measured values obtained by indirect calorimetry were compared, and subgroup analyses were conducted to compare their consistency across different subgroups. Results Among the nine equations, the Cunningham equation and the Owen equation showed relatively small deviations from the measured values, with no significant differences (deviation rates of -1.9% and -2.0%, root mean square errors of 222.7 kcal/d and 239.4 kcal/d, and coincidence rates of 48.4% and 47.5%, respectively). In subgroups stratified by gender and body mass index (BMI), the Cunningham equation showed no significant difference compared with the measured values. The Owen equation showed no significant difference compared with the measured values only in some subgroups [males with BMI of 20~ < 27 kg/m² and ≥27 kg/m², and females with BMI < 20 kg/m²]. Conclusion The Cunningham equation, which utilizes body composition data, can assess the resting energy expenditure of the elderly in pension institutions with relatively high accuracy and speed, demonstrating strong applicability in this population.

Purpose To analyze the precursor lesions,clinicopathological features and prognosis of mucinous carcinoma(MC).Methods A total of 303 MC cases diagnosed by surgi-cal specimens were included,including 193 pure mucinous car-cinomas(PMC)and 110 mixed mucinous carcinomas(MMC).PMC included 163 cases of type A(hypocellular type)and 30 cases of type B(hypercellular type).The histomorphological characteristics,surrounding breast tissue morphology,and im-mune markers were evaluated to analyze the clinicopathological features related to MC precursor lesions and prognosis.Results The median age at diagnosis of MC was 50 years,and the me-dian tumor size was 2.5 cm.Compared to PMC,MMC had more lymph node(LN)involvement,more grade Ⅲ-Ⅳ and Ki67＞20％tumors(P＜0.05).There were no significant differences in tumor size,LN involvement and clinical stage between type A and type B PMC.55 cases of MC(49 PMC and 6 MMC)with precursor lesions of mucocoele-like lesions(MLL)were all grade 1 to 2,most of them(54/55,98.2％)were T1-T2,and the proportions of MC component in all 6 MMCs were all ≥ 50％.There were 119 cases of MC whose precursor lesions were ductal carcinoma in situ(DCIS),of which 28.6％of cases(34/119)had LN involvement,and 16.8％(20/119)of cases showed high proliferative activity(Ki67＞20％).The precursor lesions of MC in 16 cases were solid papillary carcinoma(SPC)in situ,inclu-ding 7 cases of type BPMC and 9 cases of MMC.The median age of these patients was 67 years and no recurrence or metastasis was observed during follow-up.The disease-free survival(DFS)and overall survival(OS)of the 303 cases of MC was 93.5％and 98.6％,respectively.PMC had a better prognosis than MMC(DFS:95.2％vs.90.6％;OS:99.5％vs.97.2％),but there was no significant difference between type A and type B PMC.The prognosis of patients with LN involvement and clinical stage Ⅲ-Ⅳ was worse(P＜0.05).Conclusion MC of the breast is a kind of heterogeneous malignant tumors.Our findings support that MC with specific precursor lesions have different ev-olutionary pathways,that MC with precursor lesions of MLL and SPC have a good prognosis,and MC associated with high-grade DCIS are more aggressive.LN involvement,higher clinical grade,and younger age are associated with poor prognosis.Focu-sing on precursor lesions and high risk clinicopathological fea-tures can contribute to providing more effective treatments for these patients.