ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

Objective: To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome. Methods: One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website. Results: There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways. Conclusion Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.

To develop a traditional Chinese medicine （TCM） diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation， and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated， and 312 valid clinical case information collection forms were obtained， which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods， namely， differentiation analysis， Cronbach's coefficient， correlation coefficient， and stepwise regression， were used to screen out the candidate items， and Logistic regression analysis and factor analysis were used to assign weights to the items， and the final diagnostic model was determined by the receiver operating characteristic （ROC） curve， and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items： turbid dirt coating （with a weight value of 23， the same below）， sticky stools （16）， fullness in the epigastrium and abdomen （12）， dark complexion （12）， irritability （11）， brown spots on the skin （11）， heaviness of head （10）， and chest stuffiness （5）， and the degree score was 0， 0.5， 1.0， and 1.5 points corresponding to no， mild， moderate and severe symptoms， respectively. The total score was the sum of the degree score multiplied by the weighted value of each item， and when the total score reached 33 points， it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group， and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%， with the specificity of 95.90% and 89.74%， the Yoden index of 0.85 and 0.79， the positive predictive value of 95.28% and 89.47%， the negative predictive value of 90.70% and 89.74%， the diagnostic advantage ratios of 198.18 and 72.67， and the Kappa values of 0.86 and 0.79， which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.

Objective To explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P＜0.05),and there were no significant differences in other indexes(P＞0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P＜0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.

Objectives:To investigate the impact of resting heart rate on the risk of all-cause mortality in ultra-high risk atherosclerotic cardiovascular disease(ASCVD)patients. Methods:A total of 3 645 patients with ultra-high risk ASCVD(as defined in the 2023 Chinese Lipid Management Guidelines)were screened from the 2006 to 2020 Kailuan Study cohort,and after excluding 602 patients with missing resting heart rate,3 043 patients were included in the final analysis.Patients were divided into＜68 beats/min group(n=744),68-74 beats/min group(n=786),75-80 beats/min group(n=760),and≥81 beats/min group(n=753)according to the resting heart rate.Cox proportional regression model was used to estimate the hazard ratios(HRs)and 95%CI for all-cause mortality associated with the different resting heart rate groups and every 10 beats/min increase of resting heart rate.The dose-effect relationship of resting heart rate level and all-cause mortality was assessed by a restricted cubic spline regression model.The Kaplan-Meier method was applied to calculate the cumulative all-cause mortality in different groups,and the differences were compared using log-rank test. Results:The median follow-up time was 5.81(3.46,9.64)years,there were 772(25.37%)all-cause deaths during follow up.After adjusting major confounding factors,the results showed that compared with＜68 beats/min group,the risk of all-cause mortality in 75-80 beats/min group and≥81 beats/min group increased by 24%(HR=1.24,95%CI:1.01-1.52,P=0.047)and 47%(HR=1.47,95%CI:1.20-1.81,P＜0.001),respectively;the risk of all-cause mortality in 68-74 beats/min group was similar(HR=1.06,95%CI:0.86-1.31,P=0.625).In addition,an increase of 10 beats/min in resting heart rate was associated with a 13%increase in the risk of all-cause mortality(HR=1.13,95%CI:1.07-1.19,P＜0.001).In stratified analyses,it was found that for every 10 beats/min increase in resting heart rate,women faced a higher risk of all-cause mortality than men,and patients＜65 years old faced a higher risk of all-cause mortality than patients≥65 years old.The restricted cubic spline analysis also showed that resting heart rate was linearly associated with the risk of all-cause mortality(Poverall＜0.001,Pnon-linear=0.933),and the risk increased significantly with resting heart rate＞70 beats/min. Conclusions:Increased resting heart rate is linearly associated with increased risk of all-cause mortality in patients with ultra-high risk ASCVD.The appropriate intervention cut-off point of resting heart rate for ultra-high risk ASCVD patients may be＞75 beats/min.

Along with the change in lifestyle and diet, diabetes mellitus with hyperlipidemia has been a major risk and death factor for cardiovascular disease with the increasing incidence of diabetes mellitus with hyperlipidemia year by year. In order to promote and make full use of unique characteristics and advantages of TCM, the guidance writing group adopted the pattern of combination with disease and syndrome to make a standardized approach to diagnosis and treatment based on emphasis on diagnosis and treatment. Guidelines for the Diagnosis and Treatment of Diabetes Mellitus with Hyperlipidemia Combined with Disease and Syndrome (hereinafter referred to as " the Guideline") was published in the World Chinese Medicine in August, 2021. Based on the pattern of combination with disease and syndrome, the Guideline highlights the significant characteristics, such as: precise diagnosis and treatment by combined with disease and syndrome, updating criteria, rehabilitation diet therapy and exercise and following the principles which include but not limited to evidence-based medicine. According to the evidence of evidence-based medicine and expert consensus, the Guideline gives recommendations for diagnosis, treatment and rehabilitation of diabetes mellitus with hyperlipidemia. In the article, the main contents and characteristics of the new guideline were interpreted in order to provide concise and practical guidance for clinicians and promote the clinical popularization and application of the Guideline.

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objectives:To investigate the association of trajectories of atherogenic index of plasma(AIP)with the risk of atherosclerotic cardiovascular disease(ASCVD). Methods:A total of 51 831 employees and retirees who participated in Kailuan Group health examination for three consecutive times from 2006 to 2010 were included in this study.AIP was calculated using the log(triglycerides[TG]/high-density lipoprotein-cholesterol[HDL-C])formula.AIP trajectory models were fitted by the SAS Proc Traj program,and according to AIP trajectory,the subjects were divided into low stability group(n=11 114),low to moderate stability group(n=21 647),medium to high stability group(n=13 659),and high stability group(n=5 411).Kaplan-Meier method was used to calculate the cumulative incidence of ASCVD in different groups and compared by log-rank test.Cox proportional risk regression model was used to analyze the effects of different AIP trajectories on ASCVD risk. Results:Finally,51 831 patients were included in the analysis.During a mean follow-up of(10.19±2.22)years,5 142(9.92%)subjects developed ASCVD,4 013(7.74%)subjects died.Cox regression analysis after adjusting for confounding factors showed:compared with the low stability group,the risk of ASCVD increased by 13%(HR=1.13,95%CI:1.04-1.23,P=0.003)and 20%(HR=1.20,95%CI:1.10-1.31,P＜0.001)and 41%(HR=1.41,95%CI:1.27-1.57,P＜0.001)in the low to moderate stability group,moderate to high stability group and high stability group,respectively,and the risk increased gradually(Ptrend＜0.001).Stratified analysis showed that the risk of ASCVD in people aged＜65 years and low-density lipoprotein cholesterol(LDL-C)＜3.4 mmol/L with long-term high levels of AIP was higher than that in people aged≥65 years and LDL-C≥3.4 mmol/L(both Pinteraction＜0.01). Conclusions:In Kailuan Study cohort,those with long-term high levels of AIP had a higher risk of ASCVD,and the risk gradually increased.In addition,we found that the risk of ASCVD in people with long-term high levels of AIP was higher in＜65 years old than in≥65 years old,and the risk of ASCVD in people with LDL-C＜3.4 mmol/L was higher than that in people with LDL-C≥3.4 mmol/L.

Abstract OBJECTIVE Linezolid(LZD) is a synthetic oxazolidone antibacterial drug that has activity against most Gram positive bacteria. LZD is widely used in pediatric patients, and its common adverse reactions include gastrointestinal reactions and bone marrow suppression, etc. In recent years, LZD-induced hyperlactatemia has gradually attracted attention. LZD-induced hyperlactatemia can exacerbate the condition of pediatric patients and is associated with high mortality rates in children. However, there is currently a lack of data on the risk factors for LZD-induced hyperlactatemia in pediatric patients. METHODS Therefore, this paper collected and retrospectively analyzed the information of hospitalized pediatric patients who received LZD treatment at the Children's Hospital of Chongqing Medical University from October 2012 to February 2023, including demographic characteristics of pediatric patients and clinical treatment related records, etc. According to the inclusion and exclusion criteria, this paper identified whether the included pediatric patients had developed hyperlactatemia and evaluated the causal relationship between LZD and hyperlactatemia using the Naranjo's Scale. The risk factors were analyzed using univariate and multivariate logistic regression, and the dose-response relationship between risk factors and LZD-induced hyperlactatemia was further analyzed using a restricted cubic spline(RCS) model. RESULTS A total of 331 pediatric patients were included, of which 145 pediatric patients(43.8%) developed LZD-induced hyperlactatemia, including 122 cases of mild hyperlactatemia and 23 cases of severe hyperlactatemia; the causal relationship score of LZD-induced hyperlactatemia was “possibly related” in 87 cases(60.0%) and “highly likely related” in 58 cases(40.0%). The median age of pediatric patients was 3(0.92, 9) years old, with 55.29% males, 25.38% patients with liver disease, 8.76% pediatric patients with kidney disease, and 36.56% pediatric patients with cardiovascular disease; the median number of treatment days for pediatric patients receiving LZD was 13(8, 22) d, with pediatric patients with hyperlactatemia having a longer median number of LZD treatment days than those without hyperlactatemia[16(10, 28) vs 11(7, 18)]; 41.09% of pediatric patients used P-glycoprotein inducers in combination, with more pediatric patients(57.4%) experiencing hyperlactatemia; 53.47% of pediatric patients used P-glycoprotein inhibitors in combination; the median values of lactic acid baseline, creatinine baseline, and baseline estimated glomerular filtration rate(eGFR) were 0.92(0.80, 0.92)mmol·L-1, 26(18.25, 34.90) μmol·L-1, 179.97(137.23, 222.70)mL·min-1·(1.73 m)-2, respectively. Multivariate logistic regression analysis showed that pediatric patients received longer LZD treatment duration(OR=1.026, P=0.004), and the combination of P-glycoprotein inducers(OR=2.023, P=0.004), higher lactic acid baseline levels(OR=2.408, P=0.022), and lower eGFR(OR=0.997, P=0.047) were independent risk factors for LZD-induced hyperlactatemia. The RCS model showed that as the number of days of LZD treatment increases, the risk of LZD-induced hyperlactatemia increased nonlinearly(P-non-linear=0.041); when the lactic acid baseline value was -1, the risk of LZD-induced hyperlactatemia dramatically increased as the lactic acid baseline value increased, when it was >0.92 mmol·L-1, the risk of LZD-induced hyperlactatemia slowly increased as the lactic acid baseline value increased(P-non-linear=0.013). CONCLUSION This study explores for the first time the risk factors of LZD-induced hyperlactatemia in pediatric patients, including the impact of the interaction between LZD and drugs that affect mitochondrial function, P-glycoprotein inducers, and P-glycoprotein inhibitors on hyperlactatemia. RCS models are used to analyze the dose-response relationships between LZD treatment days, lactic acid baseline values, and the occurrence of LZD-induced hyperlactatemia. When LZD is combined with P-glycoprotein inducers(mainly isoniazid, rifampicin, and ethambutol), the risk of LZD-induced hyperlactatemia increases, and its related mechanisms still need further research. In addition, pediatric patients with renal insufficiency may need to adjust the LZD dosage appropriately to avoid the occurrence of hyperlactatemia. In conclusion, when pediatric patients receive LZD treatment, attention should be paid to risk factors such as lactic acid baseline value, duration of LZD use, combined use of P-glycoprotein inducers, and renal dysfunction, in order to prevent the occurrence of LZD-induced hyperlactatemia based on the pediatric patient's treatment needs.