OBJECTIVE To provide a reference for the selection of anti-infection schemes and pharmaceutical monitoring of pulmonary infection due to Alternaria alternata after renal transplantation. METHODS The clinical pharmacist was involved in the anti-infective treatment of a patient with pulmonary infection caused by A. alternata after renal transplantation. After considering the patient’s clinical symptoms， laboratory test results， and pertinent literature， clinical pharmacists determined that the patient may have developed pulmonary infection as a result of respiratory allergy due to A. alternata. The potential for infections from both Legionella and adenovirus remained a possibility. Oral administration of Voriconazole tablets was recommended for fungal therapy， while Moxifloxacin tablets were suggested for treating Legionella. Additionally， it was advised to lower the dosage of tacrolimus and stop using ganciclovir. The pharmacists meticulously tracked the patient’s voriconazole trough levels and any adverse effects that might arise during the therapy. RESULTS The physician endorsed the clinical pharmacist’s recommendations， and the patient’s status was steady， permitting discharge. CONCLUSIONS A. alternata is a potential pathogen for immunosuppressed patients， particularly when they also experience respiratory allergic reactions. Voriconazole can serve as the first-line treatment for anti-infection therapy. Clinical pharmacists ensure the patient medication safety by adjusting the dosage of voriconazole， extending the treatment course， monitoring liver and visual functions， and being vigilant about the interaction between voriconazole and immunosuppressants.

Objective To investigate the correlation between serum nickel-like protein(Metrnl)level and glycolipid metabolism and inflammatory state in patients with T2DM complicated with abdominal obesity.Methods One hundred and twenty-four T2DM patients and 140 non-diabetic controls who were hospitalized in Gansu Provincial People's Hospital from May to September 2022 were selected and divided into T2DM combined abdominal obesity group(T2DM+AO,n=81),T2DM group(n=43),abdominal obesity group(AO,n=69)and normal control group(NC,n=71)according to whether they suffered from T2DM and abdominal obesity.ELISA method was used to determine the levels of serum Metrnl,IL-4 and IL-13.The correlation between serum Metrnl and the indicators of glucose and lipid metabolism,WC,BMI,VFA,FPG,HbA1c,TC,TG,LDL-C,HDL-C and the indicators of inflammatory state,IL-4 and IL-13 were analyzed.Results Compared with NC group,serum Metrnl levels in T2DM group,AO and T2DM+AO group were decreased(P＜0.05).Serum Metrnl was negatively correlated with WC,BMI,VFA,FPG,HbA1c,TG,IL-4,IL-13(P＜0.01),and positively correlated with HDL-C(P＜0.05).Age,WC,BMI and IL-4 were the influencing factors of Metrnl.WC,VFA,FPG and Metrnl were the influencing factors of T2DM combined with abdominal obesity.The ROC curve showed that serum Metrnl had a sensitivity of 82.5%and a specificity of 93.8%for the diagnosis of T2DM with abdominal obesity.Conclusions Serum Metrnl in T2DM patients with abdominal obesity is significantly reduced,and is closely related to glucose and lipid metabolism and inflammatory status.Serum Metrnl may be a novel biomarker factor for T2DM complicated with abdominal obesity.

Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy(DCM)rats.Methods Among 60 SPF male SD rats aged 3 weeks,10 rats were randomly selected as normal control group(n=10),and the remaining 50 rats were established by peritoneal injection of streptozoto-cin combined with high-sugar and high-fat diet for DCM rat model.A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group(DCM group,n=12),low-dose liraglutide treatment group(LL group,n=12)and high-dose liraglutide treatment group(HL group,n=12).Rats in LL group(100 μg/kg)and HL group(200μg/kg)were given intraperitoneal injection of liraglutide once a day.And after 12 weeks of intervention,the rats were killed under anesthesia after echocardiography to detect cardiac function,and the heart tissues were taken for metabolomics detection.The differential metabolites and related pathways that may be related to liraglutide improving myocardial metab-olism in DCM rats were screened and enriched.Results Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in DCM group were significantly decreased,and the ra-tio of early to late diastolic mitralflow velocities(E/A)was significantly increased(P＜0.05).Compared with DCM group,LVEF and LVFS in LL group and HL group were significantly increased,and E/A ratio was significantly decreased(P＜0.05),suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated.395 metabolites were detected by metabolomics,among which 239,116 and 187 different metab-olites and 13,6 and 20 metabolic pathways were enriched in DCM group and normal control group,LL group and DCM group,HL group and DCM group.In the above three groups,29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway,caffeine metabolic pathway and valine,leucine and isoleucine bi-osynthesis pathway,among which choline metabolic pathway had the most significant differences.Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.

Objective To investigate the clinical efficacy and value of interventional treatment of iatrogenic massive vaginal bleed-ing.Methods Retrospective analysis was performed on 35 patients with postoperative vaginal massive hemorrhage in obstetrics and gynecology who were admitted.Abdominal aorta and bilateral internal iliac arteries angiography and embolization of abnormal vessels were performed under digital subtraction angiography(DS A),and relevant clinical data were recorded and analyzed.Results After interventional treatment,the vaginal bleeding of 33 patients basically stopped within 3 days,and the average interventional operation time was(57.5±17.2)min.The hemoglobin value,hematocrit and blood pressure decreased and the heart rate increased significantly before and after interventional embolization in obstetrics and gynecology,with statistical significance(P＜0.05).There were no sig-nificant changes in hemoglobin value and hematocrit between the completion of interventional embolization and 72 hours after interventional embolization(P＞0.05).The increase of blood pressure and the decrease of heart rate were statistically significant(P＜0.05).Two patients with cesarean section had poor hemostatic effect after interventional embolization,and the bleeding stopped after exploratory laparotomy and hysterectomy.Conclusion Interventional treatment has the advantages of small trauma,simple operation,signifi-cant curative effect,few adverse reactions,and rapid recovery.It plays an important role and clinical value in the diagnosis and treat-ment of iatrogenic vaginal bleeding.

Head and neck malignant tumor is one of the most heterogeneous diseases.The multi-disciplinary team(MDT)is an essen-tial component for personal precise diagnosis,treatment and integrated care management of oncologic diseases including head and neck malignant tumor.MDT clinical practice is also an important teaching mode for head and neck malignant tumors,but it is limited by time and space in actual teaching.An internet visualization platform was constructed based on the Internet,hospital HIS/PACS/LIS/EMR system,medical visualization screen,oral endoscope,remote consultation platform and other accessible audio and video terminals,and has been applied in MDT clinical teaching of head and neck malignant tumors,allowing medical students to participate in MDT through a networked visualization platform.Medical students will achieve deep learning for the most heterogeneous malignant tumor.MDT sup-ported by the internet visualization platform provides a new pathway for clinical medical education.

Objective To investigate the predictive value of lactate/albumin ratio(LAR),interleukin-6(IL-6)and CD4+T lymphocyte count in 28-day mortality in patients with severe pneumonia and sepsis.Methods A total of 73 patients with severe pneumonia and sepsis admitted to the Respiratory Intensive Care Unit(RICU)of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2022 to June 2023 were enrolled and divided into the survival group(n=43)and the death group(n=30)according to their 28-day outcomes.The clinical data of the patients were collected from their electronic medical records,including age,gender,comorbidities with hypertension,diabetes,and coronary artery heart disease(CHD),as well as sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,mean arterial pressure(MAP),confusion,uremia,respiratory rate,blood pressure,age ≥65 years(CURB-65)score,total bilirubin(Tbil),serum creatinine(Scr),platelet count(PLT),white blood cell(WBC)count,procalcitonin(PCT),and C-reactive protein(CRP)at admission to RICU.On the 1st,3rd,and 7th day after admission to RICU,the patients'arterial blood was drawn,and the lactate level was detected by a fully automated blood gas analyzer.The peripheral venous blood was drawn,and the serum albumin and IL-6 levels were detected by enzyme-linked immunosorbent assay,and the CD4+T lymphocyte subset count was measured by flow cytometry.The LAR of patients on the 1st,3rd and 7th day was calculated.The clinical data of the patients and the LAR,IL-6 level and CD4+T lymphocyte count on the 1st,3rd,and 7th day were compared between the two groups.The influencing factors of 28-day mortality in patients with severe pneumonia and sepsis were analyzed by logistic regression,and the predictive value of each influencing factor on the 28-day mortality in patients with severe pneumonia and sepsis was evaluated by the receiver operating characteristic(ROC)curve.Results There was no significant difference in gender,age,proportions of comorbidities with hypertension,diabetes and CHD,length of stay in RICU,and Tbil,MAP,PLT,Scr,WBC,PCT and CRP at admission to RICU(P＞0.05).The APACHE Ⅱ and CURB-65 scores of the patients in the death group were significantly higher than those in the survival group(P＜0.05).On the 1st,3rd and 7th day,the CD4+T lymphocyte count in the death group was significantly lower than that in the survival group,while the SOFA score was significantly higher than that in the survival group(P＜0.05).On the first day,there was no significant difference in the LAR and IL-6 level be-tween the death group and the survival group(P＞0.05).However,on the 3rd and 7th day,the LAR and IL-6 level in the death group were significantly higher than those in the survival group(P＜0.05).The LAR,IL-6 level and SOFA score on the 3rd and 7th day in the survival group were significantly lower than those on the 1st day,and these indicators on the 7th day were sig-nificantly lower than those on the 3rd day(P＜0.05);the CD4+T lymphocyte count on the 3rd and 7th day was significantly higher than that on the 1st day(P＜0.05),while it showed no significant difference on the 7th and 3r day(P＞0.05).The IL-6 level on the 7th day in the death group was significantly lower than that on the 1st and 3rd day(P＜0.05),while there was no significant difference in IL-6 level on the 1st day compared with the 3r day(P＞0.05);moreover,there was no significant difference in LAR,CD4+T lymphocyte count and SOFA score between each time point(P＞0.05).Pearson correlation analy-sis showed that on the 3rd day,the LAR and IL-6 level were significantly positively correlated with the SOFA score in patients with severe pneumonia and sepsis(r=0.385,0.394;P＜0.05).On the 7th day,the LAR and IL-6 level were also significantly positively correlated with the SOFA score(r=0.418,0.402;P＜0.05).On the 3 rd and 7 th day,CD4+T lymphocyte count was significantly negatively correlated with the SOFA score(r=-0.451,-0.454;P＜0.05).Logistic regression analysis showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day,and the IL-6 level and CD4+T lym-phocyte count on the 7th day were the influencing factors for 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The ROC curve showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day and the combination of the three,IL-6 level and CD4+T lymphocyte count on the 7th day and the combination of the two had certain predictive value for the 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The area under the ROC curve(AUC)of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day combined to predict 28-day mortality in patients with severe pneumonia and sepsis was 0.891,and the AUC of APACHE Ⅱ score for predicting 28-day mortality in pa-tients with severe pneumonia and sepsis was 0.769.The AUC values of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.795,0.757 and 0.770,respective-ly,and the AUC values of IL-6 level and CD4+T lymphocyte count on the 7th day and their combination for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.743,0.802 and 0.888,respectively.Conclusion The 3-day LAR,IL-6 level and CD4+T lymphocyte count,and the 7-day IL-6 level and CD4+T lymphocyte count after admission are re-lated to the 28-day mortality in patients with severe pneumonia and sepsis.The combined LAR,IL-6 level and CD4+T lympho-cyte count on the 3rd day can better assess the severity and prognosis of patients.

OBJECTIVE To establish a UPLC-MS/MS method for the determination of plasma concentration of three carbapenem antibiotics， i.e. ertapenem （ETP）， imipenem （IPM） and meropenem （MEM）. METHODS After protein precipitation with methanol， the plasma samples were separated by ACQUITY UPLC BEH C18 column （2.1 mm×50 mm， 1.7 μm） using stable isotopes of three antibiotics （ETP-D4， IPM-D4， MEM-D6） as the internal standard. The mobile phases were 98% acetonitrile +2% water +0.1% formic acid and 98% water +2% acetonitrile +0.1% formic acid， by gradient elution. The flow rate was 0.3 mL/min and the column temperature was 40 ℃. Scanning analysis was performed in the positive ion and multiple reaction monitoring mode. RESULTS The method had good specificity， good linearity （r2≥0.993） in the range of 0.2-200， 0.1-100 and 0.1-100 μg/mL of ETP， IPM and MEM， and good intra-batch and inter-batch precision and accuracy （all RE≤5.14%， all RSD≤11.15%）， the matrix effect and extraction recovery were consistent （RSD≤12.99%）. CONCLUSIONS This study establishes the UPLC-MS/MS method to simultaneously quantify the plasma concentration of ETP， IPM and MEM. The method has the advantages of simple pretreatment， short detection time and small sample quantity to meet clinical requirement.

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) genotype of Yersinia pestis and its regional distribution characteristics in natural plague focus of Tibet Autonomous Region. Methods:A total of 125 representative Yersinia pestis strains isolated from natural plague focus in Tibet Autonomous Region at different times, regions, hosts and vectors were selected as experimental strains, and the phenol chloroform mixed extraction method was used to extract Yersinia pestis DNA. Three pairs of CRISPR primers (for YPa, YPb, YPc locus) were used to amplify the DNA of the experimental strains, and the CRISPR genotype of Yersinia pestis was determined by sequencing. Results:All 125 strains of Yersinia pestis had three CRISPR locus: YPa, YPb, and YPc. A total of 18 spacer were found, including 8 in YPa loci, 6 in YPb loci, and 4 in YPc loci. Two new types of spacers had been discovered, namely b52 and c14. CRISPR typing revealed 10 genotypes, including G1, G7, G7-b4''', G7-b52, G7-c2 -, G8, G22, G22-a4 -, G22-b4''', and G22-c14, of which 6 were newly discovered genotypes. Among the 125 experimental strains, G7 was the main genotype, accounting for 65.6% (82/125), which was distributed in 6 prefecture level citys and 1 region of Tibet Autonomous Region. Next were G22 and G7-c2 - genetypes, accounting for 14.4% (18/125) and 11.2% (14/125), respectively. G22 gene type was distributed in Nagqu, Changdu, Lhasa citys, and Ngari Prefecture, while G7-c2 - genetype was distributed in Shigatse and Shannan cities. Conclusion:The CRISPR locus of Yersinia pestis in natural plague focus of Tibet Autonomous Region is highly polymorphic, and the Yersinia pestis strains with different genotypes have obvious regional distribution characteristics.

The amount of data generated by the human experience in medical cases of classic formulas is large and the research value is high， but how to extract valuable information from these massive data is an important problem of researches on classical formulas. It is concluded that there are many problems in the current study of human experience in classical formulas， such as large amount of data， uneven quality， weak extrapolation and clinical application， which seriously affected the evidence strength of human experience in classical formulas and the contribution to experience accumulation and theoretical support. Therefore， from the structural perspective of the research questions， this paper proposed the research ideas of human experience in medical cases of classic formulas： firstly， according to the characteristics of traditional Chinese medicine （TCM） cases， based on the PICO model， which refers parti-cipants （P）， intervention （I）， comparisons （C）， and outcomes （O）， a TCM medical record evaluation tool in line with the evidence-based concept was constructed to evaluate the quality of medical cases； secondly， constructing a standardized database of human experience in classical formulas and using data mining algorithms to explore the deep relationship hidden in human experience； finally， the clinical value evaluation is carried out to verify the effectiveness of the diagnosis and treatment rules of classical formulas to achieve clinical transformation.