Vancomycin is a glycopeptide antibiotic widely used for severe infections caused by gram-positive bacteria. Nevertheless， its clinical application is limited by a narrow therapeutic window and inter-individual differences in pharmacokinetics. Conventional dosing regimens rely on clinical experience and population pharmacokinetic models， which make precise therapy difficult. The emergence of machine learning provides new insights into tackling the above challenges. By integrating multi-dimensional data including demographic characteristics， clinical indicators and combined medications， machine learning can assist individualized medication for patients and improve the capacity for vancomycin dose prediction， in vivo exposure assessment and renal toxicity risk warning. However， the application of machine learning still faces multiple challenges such as poor data quality， weak model generalization ability and insufficient interpretability. Its clinical value needs to be further confirmed by prospective studies and external validation. Future research may consider deep integration of machine learning and population pharmacokinetic models to better support vancomycin individualized medication.

Objective To investigate the protective effect and potential mechanism of kinsenoside （KD）-the main ingredient of Anoectochilus roxburghii （AR） on alcoholic liver injury in mouse models of chronic and acute alcoholic liver injury, and provide a theoretical basis for the development of drugs for alcoholic liver injury. Methods Chronic and acute alcoholic liver injury mouse models were induced by feeding liquid diet containing 30% alcohol and gavage of high doses of alcohol （6 g/kg）, respectively. The KD （50 mg/kg） and AR （250 mg/kg） were administrated by intragastric administration. Body weight, liver index, serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST） levels, serum total triglyceride （TG） and cholesterol （TC） levels were measured; hematoxylin-eosin and oil red O staining was performed on liver tissues; lipid metabolic related genes （PPARα and SREBP1） expression levels were detected by QPCR. Results Both models of alcoholic liver injury resulted in increased hepatic transaminase activity and elevated lipids, accompanied by massive vacuolar structure and lipid droplet formation in pathological liver sections. In the chronic alcoholic liver injury model, ALT and AST were significantly reduced after KD or AR treatment （P<0.05, P<0.001）; the transcriptional activity of SREBP1 was significantly reduced after KD or AR treatment （P<0.01, P<0.05）. In the acute alcoholic liver injury model, AST was significantly reduced after KD or AR treatment （P<0.01, P<0.01）, and TG level was significantly decreased （P<0.01, P<0.01）. Conclusion KD, as the main active ingredient of AR, played a major role in hepatoprotection in mice. KD treatment significantly alleviated chronic and acute alcoholic liver injury and reduced the lipid deposition in liver; KD promoted lipolysis by increasing PPARα and inhibiting the expression of SREBP1 to reduce the synthesis and accumulation of lipids, thus exerting its role in regulating lipid metabolism, which suggested that KD, as the active ingredient of AR, could be a potential drug for the treatment of ALD.

Objective To establish a model of indirectly induced respiratory tract infection with influenza A subtypes H1N1 and H3N2 in animals,to screen influenza virus hosts,and to provide theoretical support for the clinical control of influenza viruses.Methods Fifty BALB/c mice and 50 Hartley guinea pigs were randomly divided into five groups(10 animals/group for each species):normal control group,virus infects 1 group,virus infects 2 group,close transmission 1 group,and close transmission 2 group.Mice and guinea pigs in virus infects 1 and 2 groups were administered influenza A(H1N1)and influenza A(H3N2)viruses via nasal drip.For both virus infects 1 and 2 groups,animals were housed together with those in the close transmission group at a 1∶1 ratio on the following day.On day 7,the lung function,viral titer and viral load of the nasal tissue,trachea,and lung tissue of each group were measured,and pathological changes of the trachea and lung tissue of animals in the close transmission group were evaluated.Results In mice,the viral titers and viral loads of nasal,tracheal,and lung tissues of virus infects 1 and 2 and the closely transmitted groups 1 and 2 were significantly higher(P＜0.01),pathological scores of the trachea and lung tissues were significantly higher(P＜0.01),and the FVC and FEV20 of virus infects l and 2 groups were significantly lower(P＜0.01)than those in the normal control group.The nasal tissue,trachea and lung tissues of guinea pigs in virus infects 1 and 2 groups and close transmission groups 1 and 2 showed significantly higher viral titers and viral loads(P＜0.01),significantly higher trachea and lung histopathological scores(P＜0.01),and significantly lower FVC and FEV200(P＜0.01)than those of the normal control group.Conclusions In this study,influenza A subtypes H1N1 and H3N2 were used to indirectly induce respiratory tract infections in mice and guinea pigs for analyses of animal lung function,respiratory viral titers,viral load,and pathology.The animal models of the indirect transmission of influenza viruses in the respiratory tract had certain limitations;for example,influenza viruses were transmitted less efficiently among mice than among guinea pigs.The guinea pig model was stable.These findings confirm that guinea pigs are suitable hosts for efficient virus replication and transmission.

OBJECTIVES: To investigate the therapeutic effects of inulin-type oligosaccharides of Morinda officinalis (IOMO) in a murine model of Streptococcus pneumoniae meningitis (SPM) and explore its possible mechanisms. METHODS: A total of 120 male C57BL/6J mice were randomly assigned into Sham, SPM+Saline, SPM+IOMO (25 mg/kg), and SPM+IOMO (50 mg/kg) groups. After modeling, the mice received daily gavage of saline or IOMO at the indicated doses for 7 consecutive days, and the changes in symptom scores and mortality of the mice were monitored. Brain pathology and neuronal injury of the mice were assessed using HE and Nissl staining, and qRT-PCR was performed to detect mRNA levels of the inflammatory mediators. Brain edema and blood-brain barrier (BBB) permeability of the mice were evaluated by measuring brain water content and Evans blue (EB) staining; Western blotting was used to analyze the expressions of BBB-associated proteins, and flow cytometry was employed to detect IFN‑γ expression level in the infiltrating lymphocytes. Open-field test (OFT) and novel object recognition test (NORT) were conducted to assess learning and memory ability of the mice on day 21 after modeling. RESULTS: IOMO treatment at 50 mg/kg significantly reduced the symptom scores and mortality rate of SPM mice, alleviated brain damage, and downregulated mRNA levels of IL-6, TNF‑α, IL-1β, IL-18, IFN‑γ, iNOS, NLRP3, ASC, caspase-1 and GSDMD in the brain tissue. IOMO treatment also decreased brain water content and EB leakage, upregulated VE-cadherin and occludin expressions, and suppressed AQP4, iNOS, and IFN‑γ levels of the mice. IOMO-treated mice exhibited improved learning and memory compared with the saline-treated mice on day 21 after SPM modeling. CONCLUSIONS IOMO alleviates SPM symptoms, reduces mortality, and mitigates cognitive deficits in mice possibly by suppressing cerebral inflammation and protecting BBB functions.
Animals ; Morinda/chemistry* ; Mice, Inbred C57BL ; Male ; Mice ; Meningitis, Pneumococcal/drug therapy* ; Blood-Brain Barrier/metabolism* ; Inulin/therapeutic use* ; Oligosaccharides/therapeutic use* ; Disease Models, Animal ; Interferon-gamma/metabolism* ; Brain Edema

Objective To investigate the preventive effects of lidocaine administered through different routes on cardiovascular stress responses during anesthesia tracheal intubation. Methods Total 120 patients scheduled for elective surgery under general anesthesia were randomly divided into three groups: intravenous injection group （group IV）, throat spray group （group LJ）, and control group （group CT）, with 40 patients in each. Group IV received 50 mg of lidocaine via intravenous injection 1 minute before tracheal intubation. Group LJ received 50 mg of lidocaine sprayed into the pharyngeal cavity, glottis, and subglottic area. Group CT did not receive any treatment, and the remaining procedures were performed following the routine general anesthesia induction protocol. Heart rate （HR）, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, and mean arterial pressure （MAP） were recorded at four time points: T₀ （before tracheal intubation）, T₁ （immediately after tracheal intubation）, T₂ （3 minutes after intubation）, and T₃ （5 minutes after intubation）. Statistical analysis of the data was performed using SPSS 22.0. Results There were no significant differences in HR at various time points within the group LJ. The changes in HR in the group IV and group CT were different statistically from those in the throat spray group. The blood pressure of patients in all three groups increased to varying degrees immediately after tracheal intubation, with the group CT showing particularly significant changes that differed significantly from both the group IV and the group LJ. The group LJ rapidly returned to levels close to those before intubation. Conclusion The preventive effects of lidocaine on stress responses during tracheal intubation were different depending on the route of administration. The inhibitory preventive effect of the throat spray method was superior to that of intravenous lidocaine, especially in preventing changes in heart rate.

Objective:To identify predictors of adverse pregnancy outcomes(APOs)in patients with systemic lupus erythematosus(SLE).Methods:A retrospective analysis was conducted on 318 SLE pa-tients who delivered at Peking University People's Hospital from May 2016 to September 2021.These pa-tients were categorized into two groups:The APOs group(n=85)and the non-APOs group(n=233).Various factors,including disease duration,clinical manifestations,laboratory parameters,and systemic lupus erythematosus disease activity index 2000(SLED AI-2000)scores,were analyzed for their associa-tion with APOs.SPSS 26.0 software was used to analyze the data.Results:The mean age of SLE pa-tients in this study was(24.65±5.26)years.Among the 318 pregnancies studied,302(302/318,94.97％)resulted in live births,while 16(16/318,5.03％)cases ended in stillbirths,with no neonatal deaths reported.Among the live births,206(206/302,68.21％)were full-term infants,65(65/302,21.52％)cases were small for gestational age(SGA),and 31(31/302,10.26％)cases were preterm.The SLEDAI-2000 scores were significantly higher in the APOs group compared with the non-APOs group(5.82±4.97 vs.3.74±3.72,t=4.019,P=0.001),suggesting greater disease activity as a risk fac-tor.Similarly,glucocorticoid doses were markedly higher in the APOs group[12.50(7.50,50.00)mg vs.10.00(5.00,15.00)mg,P＜0.001],underscoring the link between disease severity and APOs.Univariate analysis revealed that lupus nephritis(31.76％vs.21.03％,x2=3.946,P=0.047),throm-bocytopenia(24.71％vs.9.01％,x2=13.380,P＜0.001),hypocomplementemia(36.47％vs.26.03％,x2=4.847,P=0.028),antiphospholipid antibody positivity(20.00％vs.11.16％,x2=4.163,P=0.041),and absence of pregnancy treatment(21.18％vs.11.59％,x2=4.713,P=0.030)were associated with increased APOs risk.Multivariate Logistic regression identified thrombocyto-penia(OR=2.671,95％CI:1.309-5.449,P=0.007),hypocomplementemia(OR=1.935,95％CI:1.104-3.393,P=0.021),and antiphospholipid antibody positivity(OR=2.153,95％CI:1.054-4.399,P=0.035)as independent predictors of APOs.Conclusion:These findings highlight that certain clinical and laboratory features,including thrombocytopenia,hypocomplementemia,and antiphospholipid antibody positivity,are critical independent predictors of APOs in SLE patients.The study underscores the importance of close monitoring and proactive management of these risk factors to improve pregnancy outcomes in SLE patients.

Objective To explore the influencing factors of compliance with new oral anticoagulants(NOACs)in elderly patients with nonvalvular atrial fibrillation(NVAF)and its correlation with social support.Methods The clinical data of 126 patients with NVAF treated by NOACs in Lu 'an People's Hospital of Anhui Province from January 2022 to January 2024 were selected by convenient sampling method.General data of patients were collected.According to Morisky medication compliance scale,patients were divided into two groups:the good compliance group(n=74)and the poor compliance group(n=52).Social support was investigated by Social Support Rating Scale(SSRS).General data of patients were compared between the good compliance group and the poor compliance group.The relationship between medication compliance and social support was analyzed by Pearson correlation.Multivariate Logistic regression was used to analyze the influencing factors of patient medication compliance.Results There were statistically significant differences in educational level,the proportion of patients with anxiety and depression,CHA2DS2-VASc score,HAS-BLED score and SSRS score between the good compliance group and the poor compliance group(P＜0.05).The results of the correlation analysis showed that the medication compliance of patients was positively correlated with objective support(r=0.461),subjective support(r=0.432),support utilization(r=0.323)and SSRS score(r=0.596,P＜0.05).The results of multivariate Logistic regression analysis showed that low educational level,accompanied by anxiety,low HAS-BLED and SSRS scores were risk factors for poor medication compliance in elderly NVAF patients(P＜0.05).Conclusion Improving the social support level of elderly patients with NVAF is conducive to the formation of good medication compliance.

Objective:To identify predictors of adverse pregnancy outcomes(APOs)in patients with systemic lupus erythematosus(SLE).Methods:A retrospective analysis was conducted on 318 SLE pa-tients who delivered at Peking University People's Hospital from May 2016 to September 2021.These pa-tients were categorized into two groups:The APOs group(n=85)and the non-APOs group(n=233).Various factors,including disease duration,clinical manifestations,laboratory parameters,and systemic lupus erythematosus disease activity index 2000(SLED AI-2000)scores,were analyzed for their associa-tion with APOs.SPSS 26.0 software was used to analyze the data.Results:The mean age of SLE pa-tients in this study was(24.65±5.26)years.Among the 318 pregnancies studied,302(302/318,94.97％)resulted in live births,while 16(16/318,5.03％)cases ended in stillbirths,with no neonatal deaths reported.Among the live births,206(206/302,68.21％)were full-term infants,65(65/302,21.52％)cases were small for gestational age(SGA),and 31(31/302,10.26％)cases were preterm.The SLEDAI-2000 scores were significantly higher in the APOs group compared with the non-APOs group(5.82±4.97 vs.3.74±3.72,t=4.019,P=0.001),suggesting greater disease activity as a risk fac-tor.Similarly,glucocorticoid doses were markedly higher in the APOs group[12.50(7.50,50.00)mg vs.10.00(5.00,15.00)mg,P＜0.001],underscoring the link between disease severity and APOs.Univariate analysis revealed that lupus nephritis(31.76％vs.21.03％,x2=3.946,P=0.047),throm-bocytopenia(24.71％vs.9.01％,x2=13.380,P＜0.001),hypocomplementemia(36.47％vs.26.03％,x2=4.847,P=0.028),antiphospholipid antibody positivity(20.00％vs.11.16％,x2=4.163,P=0.041),and absence of pregnancy treatment(21.18％vs.11.59％,x2=4.713,P=0.030)were associated with increased APOs risk.Multivariate Logistic regression identified thrombocyto-penia(OR=2.671,95％CI:1.309-5.449,P=0.007),hypocomplementemia(OR=1.935,95％CI:1.104-3.393,P=0.021),and antiphospholipid antibody positivity(OR=2.153,95％CI:1.054-4.399,P=0.035)as independent predictors of APOs.Conclusion:These findings highlight that certain clinical and laboratory features,including thrombocytopenia,hypocomplementemia,and antiphospholipid antibody positivity,are critical independent predictors of APOs in SLE patients.The study underscores the importance of close monitoring and proactive management of these risk factors to improve pregnancy outcomes in SLE patients.

Objective To establish a model of indirectly induced respiratory tract infection with influenza A subtypes H1N1 and H3N2 in animals,to screen influenza virus hosts,and to provide theoretical support for the clinical control of influenza viruses.Methods Fifty BALB/c mice and 50 Hartley guinea pigs were randomly divided into five groups(10 animals/group for each species):normal control group,virus infects 1 group,virus infects 2 group,close transmission 1 group,and close transmission 2 group.Mice and guinea pigs in virus infects 1 and 2 groups were administered influenza A(H1N1)and influenza A(H3N2)viruses via nasal drip.For both virus infects 1 and 2 groups,animals were housed together with those in the close transmission group at a 1∶1 ratio on the following day.On day 7,the lung function,viral titer and viral load of the nasal tissue,trachea,and lung tissue of each group were measured,and pathological changes of the trachea and lung tissue of animals in the close transmission group were evaluated.Results In mice,the viral titers and viral loads of nasal,tracheal,and lung tissues of virus infects 1 and 2 and the closely transmitted groups 1 and 2 were significantly higher(P＜0.01),pathological scores of the trachea and lung tissues were significantly higher(P＜0.01),and the FVC and FEV20 of virus infects l and 2 groups were significantly lower(P＜0.01)than those in the normal control group.The nasal tissue,trachea and lung tissues of guinea pigs in virus infects 1 and 2 groups and close transmission groups 1 and 2 showed significantly higher viral titers and viral loads(P＜0.01),significantly higher trachea and lung histopathological scores(P＜0.01),and significantly lower FVC and FEV200(P＜0.01)than those of the normal control group.Conclusions In this study,influenza A subtypes H1N1 and H3N2 were used to indirectly induce respiratory tract infections in mice and guinea pigs for analyses of animal lung function,respiratory viral titers,viral load,and pathology.The animal models of the indirect transmission of influenza viruses in the respiratory tract had certain limitations;for example,influenza viruses were transmitted less efficiently among mice than among guinea pigs.The guinea pig model was stable.These findings confirm that guinea pigs are suitable hosts for efficient virus replication and transmission.

Objective To explore the influencing factors of compliance with new oral anticoagulants(NOACs)in elderly patients with nonvalvular atrial fibrillation(NVAF)and its correlation with social support.Methods The clinical data of 126 patients with NVAF treated by NOACs in Lu 'an People's Hospital of Anhui Province from January 2022 to January 2024 were selected by convenient sampling method.General data of patients were collected.According to Morisky medication compliance scale,patients were divided into two groups:the good compliance group(n=74)and the poor compliance group(n=52).Social support was investigated by Social Support Rating Scale(SSRS).General data of patients were compared between the good compliance group and the poor compliance group.The relationship between medication compliance and social support was analyzed by Pearson correlation.Multivariate Logistic regression was used to analyze the influencing factors of patient medication compliance.Results There were statistically significant differences in educational level,the proportion of patients with anxiety and depression,CHA2DS2-VASc score,HAS-BLED score and SSRS score between the good compliance group and the poor compliance group(P＜0.05).The results of the correlation analysis showed that the medication compliance of patients was positively correlated with objective support(r=0.461),subjective support(r=0.432),support utilization(r=0.323)and SSRS score(r=0.596,P＜0.05).The results of multivariate Logistic regression analysis showed that low educational level,accompanied by anxiety,low HAS-BLED and SSRS scores were risk factors for poor medication compliance in elderly NVAF patients(P＜0.05).Conclusion Improving the social support level of elderly patients with NVAF is conducive to the formation of good medication compliance.