Objective To investigate the regularity and characteristics of lithium carbonate-induced thyroid adverse drug reaction(ADR),to provide reference for clinical rational drug use.Methods The case reports of thyroid ADR caused by lithium carbonate in National Center for ADR Monitoring,China were retrieved,and the gender and age of patients,medication reasons,combined medication,dosage and clinical manifestations of thyroid ADR were retrospectively analyzed.Results A total of 237 cases of thyroid ADR caused by lithium carbonate were reported,the ratio of male to female was 1∶1.7,the frequency was higher in the age group of 20 to 29 years,and the proportion of drug use within the range of instruction dosage was 97.8％.According to the statistics of drugs used in combination,the most drugs were for mental disorders,and the time of ADR occurrence was mostly 10 to 30 days after taking the drug.The main clinical manifestations of thyroid ADR were hypothyroidism,goiter and hyperthyroidism.Conclusion Lithium carbonate-induced thyroid ADR mostly occurred at the therapeutic dose,which was related to the patient's gender,age,combined medication and other factors.Clinicians and pharmacists should master the rules and characteristics of thyroid ADR caused by lithium carbonate,timely detect and treat ADR,to provide guarantee for the safety of patients' medication.

Objective:To investigate the impact of metformin on the Beh?et's disease (BD) mice model via the Treg/Th17 axis.Methods:The BD mice model was established by subcutaneous injection of HSV-1. Four groups were established, including healthy control group, model group, high-dose metformin group, and low-dose metformin group. The HSV-1 DNA copy number in the peripheral blood was measured using qRT-PCR. Plasma levels of TGF-β 1, IL-10, IL-17, IL-23, IL-6, and TNF-α were assessed by ELISA. Flow cytometry was employed to determine the proportion of Treg and Th17 cells in the spleen. One-way analysis of variance was used for inter-group comparisons, pairwise comparisons were performed using SNK- q test. Results:Thirty-eight BD models were successfully established, with 28 survived. Compared to the BD model group, the metformin treatment groups showed faster healing of genital ulcers, joint redness/swelling, and skin ulcers, along with better mental status. HSV-1 copy numbers decreased in the metformin groups compared to the model group at 20 and 30 days post-treatment. Compared to the healthy control group, the model group exhibited elevated levels of TGF-β 1, IL-17, IL-6, IL-23, and TNF-α, but a decrease in IL-10. Following high-dose metformin treatment, TGF-β 1, IL-17, IL-6, IL-23, and TNF-α were significantly reduced ( q=16.17, P<0.001; q=8.76, P<0.001; q=6.78, P=0.004; q=4.45, P=0.020; q=12.08, P<0.001), accompanied by elevated IL-10 (specific value) ( q=6.28, P<0.001). Compared with the control group [Treg: (1.82±0.68)%; Th17: (2.12±0.86)%], the model group showed significantly elevated proportions of Treg cells[(6.03±2.42)%] ( q=5.01, P<0.001) and Th17 cell [(3.40±0.58)%] ( q=2.96, P=0.017). After high-dose metformin treatment, both Treg cell proportion [(3.20±1.66)%] and Th17 cell proportion [(2.16±0.78)%] decreased compared to the model group ( q=3.05, P=0.014). No significant differences were observed between the high-and low-dose metformin groups across all measured indicators, indicating similar efficacy. Conclusion:Metformin could reduce HSV-1 virus replication, reduce the levels of inflammatory cytokines and regulate Treg/Th17 axis to alleviate the BD symptoms. This study provides evidence for repurposing metformin in the treatment of Beh?et's disease.

Objective Heart failure(HF)complicated by acute kidney injury(AKI)significantly impacts patient outcomes,and it is crucial to make early predictions of short-term mortality.This study is focused on developing an interpretable machine learning model to enhance early prediction accuracy in such clinical scenarios.Methods This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ,version 2.0)database.Data from the first 24 hours after admission to the ICU were extracted and divided into a training set(70％)and a validation set(30％).We utilized the SHapley Additive exPlanation(SHAP)method to interpret the workings of an extreme gradient boosting(XGBoost)model and identify key prognostic factors.The XGBoost model's predictive ability was evaluated against three other machine learning models using the area under the curve(AUC)metric,and its interpretation was enhanced using the SHAP method.Results The study included 8 028 patients with HF complicated by AKI.The XGBoost model outperformed the other models,achieving an AUC of 0.93(95％confidence interval[CI]:0.78-0.94;accuracy=0.89),while neural network model showed the worst performance(AUC=0.79,95％CI:0.77-0.82;accuracy=0.82).Decision curve analysis showed the superior net benefit of the XGBoost model within the 9％to 60％threshold probabilities.SHAP analysis was performed to identify the top 20 predictors,with age(mean SHAP value 1.29)and Glasgow Coma Scale score(mean SHAP value 1.24)emerging as significant factors.Conclusions Our interpretable model offers an enhanced ability to predict mortality risk in HF patients with AKI in ICUs.This model can be used to assist in formulating effective treatment plans and optimizing resource allocation.

Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

BACKGROUND:Monounsaturated fatty acids are mostly recognized as a fatty acid with beneficial effects on human health,and some studies have suggested that they may contribute to non-inflammatory pain at multiple sites in the body.OBJECTIVE:To investigate the effect of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality,thereby providing potential biomarkers and intervention strategies for low back pain management and prevention.METHODS:A Mendelian randomization method was used to analyze the potential association of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality in conjunction with large sample data from the National Health and Nutrition Examination Survey(NHANES)database.Results were validated and sensitivity analyzed using multiple statistical models(e.g.,inverse variance weighting,MR-Egger regression,simple median,weighted median,and weighted median)to enhance the reliability of causal inferences.In the NHANES study,multivariate Cox proportional risk regression models were used to assess the independent predictive values of different fatty acid ratios and to control for confounders.Potential nonlinear relationships between monounsaturated fatty acids and all-cause mortality were assessed using Kaplan-Meier curves,log-rank tests,and restricted cubic spline curves.RESULTS AND CONCLUSION:Elevated monounsaturated fatty acids have been found to be associated with a significantly higher risk of low back pain,suggesting an unfavorable effect of this fatty acid.Also,monounsaturated fatty acids may increase all-cause mortality in patients with low back pain.This provides new insights into the potential effects of monounsaturated fatty acids on low back pain and all-cause mortality,and provides a scientific basis for nutritional interventions for low back pain.The results support the use of dietary modification as one of the strategies for the prevention and management of low back pain in the European population,but further studies are needed to explore the specific biological mechanisms and potential for clinical application,thereby improving guidance for the prevention and treatment of diseases in China.

Objective To assess the efficacy of tandem mass spectrometry-specific indicators in diagnosing β-ketothiolase deficiency(BKD)and to elucidate the associated gene variations contributing to the corresponding pathogenic phenotype,thereby facilitating rapid and accurate diagnosis of BKD.Methods Data from tandem mass spectrometry(MS/MS)screening of dried blood spots collected from 16,071 children between January 2018 and December 2021,along with results from gas chromatography-mass spectrometry(GC-MS)analysis and high-throughput sequencing of positive cases,were analyzed retrospectively.The study aimed to evaluate the contribution of specific MS/MS indicators in the clinical diagnosis of BKD and to trace the genetic etiology of this disease.Results Among the 16 071 subjects screened by MS/MS,37 cases(2.30‰)exhibited elevated C5OH levels,41 cases(2.55‰)showed increased C5∶1 levels,and 2 cases were diagnosed with BKD based on GC-MS analysis.When diagnosing BKD using C5OH as a single indicator,the false positive rate was 0.22%,which is lower than that of C5∶1(0.24%).The positive predictive value for C5OH was 5.40%,higher than that of C5∶1(4.88%).Among the 16 071 pediatric patients,only 2 cases were diagnosed with BKD due to elevated C5OH combined with increased C5∶1 levels,resulting in a positive predictive value of 100%.Whole exome sequencing of these two BKD patients revealed that both carried acetyl-CoA acetyltransferase 1(ACAT1)gene double allele missense heterozygous mutations.The four previously unreported mutation sites were c.949G>C(p.Asp317His),c.1063G>A(p.Ala355Thr),c.146G>A(p.Arg49Lys),and c.700G>A(p.Glu234Lys).These findings provide novel insights into the genetic basis of BKD.Conclusions The MS/MS screening indicator C5OH demonstrates superior diagnostic efficacy compared to C5∶1 in diagnosing BKD,as evidenced by lower false positive rates and higher positive predictive values.When diagnosing BKD,the use of combined indicators significantly enhances the accuracy of biochemical diagnosis compared to single indicators.Exome sequencing revealed that all BKD patients carried previously unreported mutations in the ACAT1.

Objective To review the clinical characteristics of Slackia exigua infections for improving the diagnosis and treatment.Methods We reviewed the clinical characteristics of a case of pulmonary abscess caused by Slackia exigua.The infection cases caused by Slackia exigua were searched and retrieved from PubMed,CNKI,and Wanfang databases,for the articles published during the period from January 1,2011 to December 31,2023.Results Among the 15 cases of Slackia exigua infection,84.6％(11/13)had underlying diseases.Hypertension was the most common underlying disease,reported in 54.5％(6/11)of patients.Fever was present in 73.3％(11/15)of patients.Oral diseases and abscess caused by Slackia exigua were found in 63.6％(7/11)and 60.0％(9/15)of patients,respectively.Mixed infection was identified in 33.3％(5/15)of patients.The bacterium was susceptible to penicillin,ampicillin-sulbactam,ceftriaxone,levofloxacin and clindamycin,but mostly(2/3)resistant to metronidazole.Conclusions Slackia exigua infection often originates from oral aspiration and can cause abscess.Beta-lactam antibiotics are preferred for treatment of Slackia exigua infections.More data are required to confirm whether metronidazole is effective.