OBJECTIVE To construct a predictive model for evaluating the efficacy of a triple antiemetic regimen （neurokinin- 1 receptor antagonist+5-hydroxytryptamine 3 receptor antagonist+dexamethasone） for preventing nausea and vomiting induced by highly emetogenic chemotherapy （HEC） based on interpretable deep learning algorithms. METHODS Clinical data of cancer patients who received HEC and were treated with the standard triple antiemetic regimen in the oncology department of Tianjin Medical University General Hospital from January 2018 to December 2022 were collected retrospectively. Demographic， clinical and metabolism-related variables were integrated. After data pre-processing， two deep learning algorithms （deep random forest and dense neural network） and four machine learning algorithms （support vector machine， categorical boosting， random forest and decision tree） were used to build predictive models. Subsequently， model performance evaluation and model interpretability analysis were conducted. RESULTS Among the six candidate models， the deep random forest model demonstrated the best predictive performance on the test set， with an area under the receiver operating characteristic curve of 0.850， an accuracy of 0.911， a precision of 0.805， a recall of 0.783， an F1 score of 0.793， and a Brier score of 0.075. Interpretability analysis revealed that creatinine clearance rate （Ccr） was the key predictive factor， and low Ccr levels， female gender， younger age， highly emetogenic drugs （particularly cisplatin-containing chemotherapy regimens）， and anticipatory nausea and vomiting were positively correlated with the risk of HEC-related nausea and vomiting. CONCLUSIONS The deep random forest model exhibits the best performance in predicting the efficacy of triple antiemetic regimen for preventing HEC-related nausea and vomiting. The key predictors in this model primarily include Ccr，anticipatory nausea and vomiting， gender， age， and highly emetogenic drugs.

OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate （TRV130） in improving postoperative cognitive dysfunction （POCD） in elderly rats based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway. METHODS Rats were randomly divided into the control group （normal saline）， the model group （normal saline）， the TRV130 group （2.8 mg/kg）， the TLR4/NF-κB pathway inhibitor （TAK-242） group （3 mg/kg）， the β -arrestin inhibitor （Barbadin） group （3 mg/kg）， and the traditional opioid drug （morphine） group （2.8 mg/kg）， with 15 rats in each group. Except for the control group， POCD models were established in all other groups. From the first day after surgery， drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration， the pathological damage of hippocampal tissue was observed； the cognitive function， serum inflammatory factor levels， hippocampal neurons apoptosis rate， and the expression of ionized calcium-binding adapter molecule 1 （Iba-1）， glial fibrillary acidic protein （GFAP）， and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group， the neurons in the CA1 region of the hippocampus were disordered and sparse， with decreased number， pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group， the escape latency， serum levels of tumor necrosis factor α （TNF-α）， interleukin-6 （IL-6）， and IL-1β， hippocampal neurons apoptosis rate， average fluorescence intensities of Iba-1 and GFAP， mRNA expression levels of TLR4 and NF-κB p65， and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group （ P ＜0.05）； the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased （ P ＜0.05）. Compared with the model group， the cognitive function， pathological， inflammatory， and apoptosis-related indicators were significantly improved in the TRV130 group， TAK-242 group， and Barbadin group （ P ＜0.05）； the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group （ P ＜0.05）. CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.

Objective:To investigate the effectiveness of combined teaching method integrating case-based teaching method(CBL),problem-based teaching method(PBL),and team-based teaching method(TBL)in clinical nursing teaching in pediatric intensive care unit(PICU).Methods:A total of 60 nursing students who trained in our PICU from Jan 2021 to Jun 2022 were selected as the control group,and 60 nursing students who trained in our PICU from Jul 2022 to Jun 2024 were selected as the research group.The control group received conventional nursing teaching mode,while the research group received combined teaching mode of CBL,PBL,and TBL.The scores of academic performance,logical thinking ability,self-learning ability,and clinical nursing comprehensive ability between the two groups were compared.Result:The scores of theoretical knowledge,operational skills,post-teaching Critical Thinking Disposition Inventory-Chinese Version(CTDI-CV)scale,self-directed learning readiness scale for nursing,and Mini-clinical evaluation exercise scale(Mini-CEX)in the research group were higher than those in the control group(P＜0.05).Conclusion:The combined teaching method of CBL,PBL,and TBL can effectively improve clinical nursing teaching results and comprehensive abilities of nursing students.

Objectives:To analyze the disease burden and trends of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and provide a basis for disease prevention and management.Methods:Based on the Global Burden of Disease(GBD)2021 data,we compared the age-standardized mortality rate(ASMR)and age-standardized disability-adjusted life year rate(ASDR)of ischemic stroke attributable to major metabolic risk factors(including overweight/obesity,hypertension,elevated low-density lipoprotein cholesterol,low bone density,hyperglycemia,and impaired renal function)in China and globally,and estimated their time trends through estimated annual percentage change(EAPC).We also analyzed the number of deaths,mortality rate,disability adjusted life year(DALY),and DALY rate of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and compared the epidemiological differences among different gender and age groups.Results:From 1990 to 2021,the disease burden of ischemic stroke attributable to major metabolic risk factors in China showed a slight upward trend(1990 to 2005)and then gradually decreased,with a relatively small overall decline.,while the global disease burden showed a decreasing trend.In 2021,the ASMR and ASDR of ischemic stroke attributable to major metabolic risk factors in China were 48.11/100 000 and 898.35/100 000(EAPC[95%CI]were-0.24%[-1.13%to 0.66%]and-0.25%[-1.00%to 0.51%]),respectively,both higher than the global average levels(33.96/100 000 and 651.46/100 000,EAPC[95%CI]were-1.75%[-2.03%to 1.47%]and-1.49%[-1.74%to-1.23%],respectively).Compared with 1990,the actual mortality rate and DALY rate of ischemic stroke attributable to major metabolic risk factors in China increased by 139.60%and 110.53%respectively in 2021.There are gender differences in the disease burden of ischemic stroke attributable to major metabolic risk factors in China,with significantly higher death numbers,mortality rates,DALY,and DALY rates in males compared to females.At the age level,DALY and DALY rates were both higher in individuals aged 15-49,DALY increased but DALY rates decreased in individuals aged 50-69.DALY surged in individuals aged 70 and above,male DALY rates showed increasing trend and female DALY rates showed slightly decreasing trend.Conclusions:The disease burden of ischemic stroke in China is significantly affected by metabolic risk factors.Although prevention and control have achieved certain positive results,the overall disease burden in China is higher than that of the world,and precise intervention strategies need to be developed for different genders and ages in China.

Objective:To analyze the occurrence and influencing factors of adverse reactions in patients with inflammatory bowel disease (IBD) during the long-term treatment with vedolizumab (VDZ).Methods:The study was a retrospective observational design. The study subjects were selected from patients who long-termly used VDZ to treat moderate-to-severe active IBD in Tianjin Medical University General Hospital from February 1, 2021 to December 31, 2023. Clinical data of patients were collected through the hospital system of clinical pharmacy management, including general information, IBD condition, VDZ maintenance treatment plan, combination of drugs, laboratory test results, etc. The adverse reactions of VDZ were screened and their clinical manifestations, severity, intervention and outcomes were analyzed descriptively. The patients were divided into 2 groups according to whether VDZ adverse reactions occurred, and the differences in clinical data between them were compared; the influencing factors of adverse reactions were analyzed by multivariate logistic regression method.Results:A total of 142 patients were included in the study, including 81 males and 61 females, aged (37.6±6.4) years with a range from 18 to 57 years. There were 103 patients (72.5%) developed VDZ adverse reactions, which mainly involved skin (52 patients, account for 50.5%), digestive system (33 patients, account for 32.0%) and respiratory system (18 patients, account for 17.5%). All 103 patients did not stop VDZ treatment, and the adverse reaction symptoms disappeared or were relieved after symptomatic treatments. Compared with patients without VDZ adverse reactions, the age of patients with VDZ adverse reactions were higher [(39.5±5.4) years vs. (32.4±6.7) years], and the proportions of patients with chronic relapsing clinical type [65.0%(67/103) vs. 41.0%(16/39)], severe disease activity [60.2%(62/103) vs. 33.3%(13/39)], combined drug use [67.0%(69/103) vs. 46.2%(18/39)], and injecting VDZ once every 4 weeks during maintenance treatment [27.2%(28/103) vs. 10.3%(4/39)] in the group were larger, with statistical significance (all P<0.05). Multivariate logistic regression analysis showed that the chronic relapsing clinical type [odds ratio ( OR)=1.012, 95% confidence interval ( CI): 1.001-1.028, P=0.002], severe disease activity ( OR=1.096, 95% CI: 1.010-1.158, P=0.040), combination drugs ( OR=1.035, 95% CI: 1.003-1.122, P=0.041), VDZ maintenance therapy injection interval of 4 weeks ( OR=1.014, 95% CI: 1.002-1.113, P=0.005) were the risk factors for VDZ adverse reactions. Conclusions:Among IBD patients receiving long-term treatment of VDZ, the incidence of adverse reactions of VDZ was 72.5%, mainly involving skin, digestive system and respiratory system. Symptomatic treatments could be given, and the prognosis was good. Patients with chronic relapsing clinical type, severe disease activity, combination therapy, and shorter VDZ maintenance injection interval were at higher risk of adverse reactions.

A 12-year-old male child with severe pneumonia received anti-infection therapy with cefoperazone sodium and sulbactam sodium (3 g by intravenous infusion, once every 8 hours) and minocycline (100 mg twice daily orally). After 8 days, the child experienced severe headache, accompanied by blurred vision and nausea. The head magnetic resonance imaging and 4-hour video electroencephalogram showed no abnormalities in the child. Cerebrospinal fluid pressure measured by lumbar puncture was 220 mmH 2O, and cerebrospinal fluid biochemistry and routine examination showed no abnormalities. After excluding intracranial infection, toxic encephalopathy, intracranial hemorrhage, and space-occupying lesions, it was considered that the increase of intracranial pressure was caused by minocycline. After discontinuing minocycline and administering symptomatic treatments such as mannitol, nonsteroidal anti-inflammatory drugs for 3 days, his headache was relieved. At 1-week and 1-month follow-up, no abnormal symptoms such as headache recurred in the child.

Objectives:To analyze the disease burden and trends of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and provide a basis for disease prevention and management.Methods:Based on the Global Burden of Disease(GBD)2021 data,we compared the age-standardized mortality rate(ASMR)and age-standardized disability-adjusted life year rate(ASDR)of ischemic stroke attributable to major metabolic risk factors(including overweight/obesity,hypertension,elevated low-density lipoprotein cholesterol,low bone density,hyperglycemia,and impaired renal function)in China and globally,and estimated their time trends through estimated annual percentage change(EAPC).We also analyzed the number of deaths,mortality rate,disability adjusted life year(DALY),and DALY rate of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and compared the epidemiological differences among different gender and age groups.Results:From 1990 to 2021,the disease burden of ischemic stroke attributable to major metabolic risk factors in China showed a slight upward trend(1990 to 2005)and then gradually decreased,with a relatively small overall decline.,while the global disease burden showed a decreasing trend.In 2021,the ASMR and ASDR of ischemic stroke attributable to major metabolic risk factors in China were 48.11/100 000 and 898.35/100 000(EAPC[95%CI]were-0.24%[-1.13%to 0.66%]and-0.25%[-1.00%to 0.51%]),respectively,both higher than the global average levels(33.96/100 000 and 651.46/100 000,EAPC[95%CI]were-1.75%[-2.03%to 1.47%]and-1.49%[-1.74%to-1.23%],respectively).Compared with 1990,the actual mortality rate and DALY rate of ischemic stroke attributable to major metabolic risk factors in China increased by 139.60%and 110.53%respectively in 2021.There are gender differences in the disease burden of ischemic stroke attributable to major metabolic risk factors in China,with significantly higher death numbers,mortality rates,DALY,and DALY rates in males compared to females.At the age level,DALY and DALY rates were both higher in individuals aged 15-49,DALY increased but DALY rates decreased in individuals aged 50-69.DALY surged in individuals aged 70 and above,male DALY rates showed increasing trend and female DALY rates showed slightly decreasing trend.Conclusions:The disease burden of ischemic stroke in China is significantly affected by metabolic risk factors.Although prevention and control have achieved certain positive results,the overall disease burden in China is higher than that of the world,and precise intervention strategies need to be developed for different genders and ages in China.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

OBJECTIVE To analyze the medication needs of parents of pediatric children in our hospital regarding drug instructions， and explore improvement strategies， thereby providing a basis for clinically guiding the rational use of drugs in pediatric patients. METHODS A self-designed questionnaire was used to randomly select the parents of pediatric patients in the pediatric outpatient and emergency departments of our hospital from July 1st to September 30th， 2024. A randomized face-to-face survey was conducted regarding their willingness to read drug instructions， their current understanding status， and their needs. The survey results were then statistically analyzed. RESULTS A total of 300 questionnaires were distributed in this survey， and 299 valid questionnaires were recovered， with an effective recovery rate of 99.7%. Before medication， the parents who “always” and “often” read the drug instructions in detail accounted for 39.1% （117 respondents） and 35.1% （105 respondents）， respectively. Statistically significant differences were observed in the willingness to read drug instructions among respondents with varying educational levels and occupations （P＜0.05）. Among the 299 respondents， only 48 people （16.1%）“ fully understood” the drug instructions， and the average understanding score of all the respondents was （3.77±0.83） points. The stronger the respondents’ willingness to read drug instructions， the higher their understanding scores of drug instructions （P＜0.05）. A total of 256 respondents thought that drug instructions were of great help to themselves， and the average helpfulness rating score of all the respondents was （4.28±0.78） points. Under the conditions of varying ages， educational levels， occupations， and willingness to read drug instructions， statistically significant differences were observed in the scores representing the degree of helpfulness of drug instructions to the respondents （P＜0.05）. Respondents paid the most attention to content in drug instructions such as “dosage and administration method”，“ adverse reactions”， and “indications and therapeutic categories”. The most difficult sections for them to understand included “chemical structure and properties”， “pharmacological and toxicological effects” ， and “pharmacokinetics”， etc. The demographic characteristics of the respondents were not significantly associated with the content areas of drug instructions they most desired to see improved （P＞0.05）. Most respondents （86.0%） hoped to improve the instructions mainly by “simplifying professional terms to make them more accessible”. Others included “highlighting key information” （60.5%） and “providing more detailed medication guidance” （49.2%）， etc. CONCLUSIONS Parents of pediatric patients in our hospital have a high demand for drug instructions but low comprehension. The pharmacy department should make targeted improvements to drug instructions based on parents’ actual needs， helping them accurately obtain medication knowledge and reduce potential medication safety risks.