Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1 and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61％-113.24％and 101.99％-109.37％,respectively.The matrix factors normalized by internal standard were 106.68％-111.27％and 95.70％-97.81％for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0％.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.

AIM:To compare the recovery of psy-chomotor function after intravenous anesthesia with remazolam or propofol compound alfentanil in patients undergoing painless gastrointestinal en-doscopy.METHODS:78 patients undergoing pain-less gastrointestinal endoscopy were randomly di-vided into group RA and group PA.Remiazolam or propofol combined with alfentanil were given intra-venously in group RA or group PA.The blood pres-sure,heart rate,respiratory rate and saturation of puls oxygen were recorded before procdure(T1),during checking(T2),awaking from anaesthesia(T3)and at discharging from PACU(T4).Psychomo-tor function,as measured by the Trieger's dot test(TDT)and digit symbol substitution test(DSST),were evaluated before anesthesia(T1),at discharg-ing from PACU(T4),1 h(T5)and 2 h(T6)after checking.RESULTS:From assessment of the TDT,number of dots missed(NDM),maximum distance of dots missed(MDDM)and average distance of dots missed(ADDM)at T4,T5 were significantly lower than those at T1 in two groups.The comple-tion rates and accuracy rates of DSST at T4,T5 were significantly lower than those at T1.Results of TDT and DSST at T6 were not significantly differ-ent to those at T1.The results of NDT,MDDM and ADDM at T4,T5 in group RA were significantly low-er than those in group PA.The completion rates and accuracy rates of DSST at T4,T5 in group RA increased significantly compared with group PA.Compared to group PA,the incidence of hypoten-sion was significantly lower in group RA.There was no significant difference in the incidence of respira-tory depression between the two groups.CONCLU-SION:Psychomotor function was fully recovered 2 h after surgery when remazolam compound alfent-anil was used for painless gastrointestinal endosco-py.Compared with propofol,psychomotor function recovery in the remazolam group was faster and there were fewer adverse effects after surgery in group RA.

Objective To establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis(AD)and explore the feasibility of modeling by comparing 2,4-dinitrochlorobenzene(DNCB)-induced atopic dermatitis model of mouse,"external dampness+improper diet+irrigation of senna"-induced spleen deficiency and dampness stagnation syndrome model of mouse,as well as both in combination of model mouse.Methods The construction of a mouse(Balb/c)with spleen deficiency and dampness stagnation syndrome was explored by using the method of"external dampness+improper diet+irrigation of senna",and then DNCB was applied to induce the AD-like lesions in Balb/c mice to establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.The general condition and body weight of mice in each group were observed,and the symptoms of spleen deficiency and dampness were scored.The severity of AD was evaluated by comparing the skin lesion degree,EASI score,transcutaneous water loss value(TEWL),spleen index and thymus index.The levels of creatinine,glucose,total cholesterol,triglyceride,gastrin,and amylase were measured.Results(1)During the modeling period of spleen deficiency and dampness stagnation syndrome,compared with the normal group,spleen deficiency and dampness stagnation syndrome group,spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group showed obesity,listlessness,filthy and greasy hair,diarrhea,and poor cleanliness around the anal.After combining with the application of the atopic dermatitis model,the body weight of the mice in atopic dermatitis group(P＜0.001),spleen deficiency and dampness stagnation syndrome group(P＜0.05)and spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group(P＜0.001)decreased sharply compared with the normal group.(2)Compared with the atopic dermatitis group,the degree of skin lesions,EASI score(P＜0.05)and TEWL(P＞0.05)were higher in the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group.(3)Compared with the normal group,the spleen index of the atopic dermatitis group increased(P＜0.001)and the thymus index decreased(P＜0.001).Compared with the atopic dermatitis group,the spleen index(P＞0.05)and thymus index(P＜0.05)of the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group decreased.(4)The results of serum biochemical indexes showed that compared with the normal group,the levels of creatinine(P＜0.01),glucose(P＜0.001),total cholesterol(P＞0.05),triglyceride(P＞0.05)and gastrin(P＜0.001)in the spleen deficiency and dampness stagnation syndrome group were increased,and the level of amylase was decreased(P＜0.01).Compared with the atopic dermatitis group,the levels of creatinine(P＞0.05),glucose(P＜0.05),total cholesterol(P＞0.05),triglyceride(P＞0.05),gastrin(P＜0.001)increased and the level of amylase decreased(P＞0.05).Conclusion A mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis,which was induced by the combination of DNCB and"external dampness+improper diet+irrigation of senna",can not only show obvious TCM indications of spleen deficiency and dampness syndrome,but also show the characteristics of AD.This model can be used as a reliable animal model of combination of disease and syndrome.It provides reference for further study on pathological mechanism,pharmacodynamic evaluation and pharmacological mechanism of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Third space fluid(TSF) is a common complication of advanced malignancies, including malignant pleural effusion, malignant ascites, intracranial effusion, and pelvic effusion, etc. The pharmacokinetics(PK) of anti-tumor drugs in vivo are influenced by various factors, and TSF is one of the potential factors that contributes to PK variations, which may consequently affect the efficacy and safety of anti-tumor drugs. This paper aimed to comprehensively investigate PK studies related to anti-tumor drugs in patients with malignant tumors accompanied by TSF. The paper summarized the PK characteristics of common cytotoxic drugs, small molecule targeted drugs, and monoclonal antibodies in both blood and TSF.

Objective:To evaluate the dose-response relationship of alfentanil inhibiting gag reflex when combined with propofol in elderly patients undergoing painless gastroscopy.Methods:Patients of American Society of Anesthesiologists physical statusⅠor Ⅱ, aged ≥60 yr, scheduled for elective painless gastroscopy, were selected. Propofol 1.5 mg/kg combined with alfentanil was given intravenously in all the patients. The dose of alfentanil was determined by the Dixon up-and-down method. The initial dose of alfentanil was set at 5 μg/kg. The dose of alfentanil in the next patient was determined according to the development of gag reflex, and the ratio between the two successive doses was 1.1. The median effective dose (ED 50) and 95% confidence interval of alfentanil-induced inhibition of gag reflex when combined with propofol in elderly patients undergoing painless gastroscopy were calculated using the by up-and-down sequential allocation. Results:The ED 50 (95% confidence interval) of alfentanil-induced inhibition of gag reflex when combined with propofol 1.5 mg/kg was 2.8 (2.4-3.2) μg/kg in elderly patients undergoing painless gastroscopy. Conclusion:When combined with propofol 1.5 mg/kg, the ED 50 of alfentanil inhibiting gag reflex is 2.8 μg/kg in elderly patients undergoing painless gastroscopy.

Objective:To evaluate the relationship between postoperative acute kidney injury (AKI) and preoperative dehydration in the patients undergoing surgery for gastrointestinal tumor.Methods:A total of 231 patients, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, aged≥18 yr, undergoing elective surgery for gastrointestinal tumor with general anesthesia, were enrolled.Preoperative dehydration index was calculated according to preoperative urine color, specific gravity, osmotic pressure and creatinine.Preoperative dehydration was defined as dehydration index≥3.5.AKI was defined according to the Kidney Disease Improving Global Outcomes criteria.Logistic regression analysis was conducted to assess the association between preoperative dehydration and postoperative AKI.Results:Of the 231 patients who met our inclusion criteria, 27 (11.7%) developed postoperative AKI, and 13 patients (48.1%) had preoperative dehydration among the patients developed postoperative AKI.The results of logistic analysis showed that preoperative dehydration was an independent risk factor for postoperative AKI in the patients undergoing surgery for gastrointestinal tumor ( OR=4.03, 95% confidence interval 1.72-9.39). Conclusion:Preoperative dehydration is an independent risk factor for postoperative AKI in the patients undergoing surgery for gastrointestinal tumor.

Objective:To treat the mixed and deeper infantile hemangioma with ladder dosage propranolol, and to explore its efficacy and safety.Methods:A total of 98 infants with hemangioma were treated by ladder treatment of propranolol.Before treatment,comprehensive assessments of electrocardiogram(ECG),heart color ultrasound, blood glucose,liver function,kidney function,myocardial enzymes and blood routine were conducted.After excluding contraindications,the dose of propranolol incrementally doubled from 0.5 mg·kg-1·d-1 to 4.0 mg·kg-1·d-1.Propranolol was taken 3 times a day.Before and after medication for 1 and 2 h,ECG was monitored.The changes of tumor size,texture,color and other changes or an onset of adverse reactions were dynamicly observed.The infants were visited every month.The efficacy was evaluated using Achauer system.Results: After medication,98 cases had different degrees of color changes or tumor consistency softening.After the dosage of propranolol was increased to 4.0 mg·kg-1·d-1,the change of tumor was the fastest.According to the 4-grade method, there were 84 cases(85.71%) as gradeⅣ (excellent),2 cases (2.04%) as grade Ⅲ (good),4 cases (4.08%) as gradeⅡ (medium)and 8 cases (8.16%) as gradeⅠ (poor).The curative effect of mixed hemangioma was better than that of deeper hemangioma(P<0.05).The recovery time of 74 cases of hemangiomas was 6 months.The major adverse reactions were heart rate decline(5/98,5.10%),drowsiness(3/98,3.06%),diarrhea(7/98,7.14%),loss of appetite (1/98,1.02%), and convulsions (2/98,2.04%).After treatment,all adverse reactions disappeared.Two months after drug withdrawal there were 4 cases of recurrence,and they were continously treated with propranolol.Conclusion: The efficacy of oral ladder dosage propranolol in treatment of mixed and deeper infantile hemangioma is increased significantly and there are no significant adverse reactions.

Objective To analyze and compare the anti-HCV reactivity,HCV nucleic acid detection results and HCV recom binantion immunoblot assay(RIBA) confirmatory test results in blood donors.Methods The blood samples collected from the volunteer blood donors from October 2013 to March 2015 were performed the HCV screening by using the domestic ELISA reagents from two different manufacturers and an imported nucleic acid detection reagent and matching detection system.The samples of anti-HCV reactivity or/and NAT detection positive were performed RIBA.Then the results of reactivity detected by two kinds of ELISA reagents,nucleic acid detection reagent and RIBA confirmatory test results were analyzed and compared.Results A total of 133959 samples of volunteer blood donors were detected,in which 113 380 samples covered the nucleic acid detection results,the reactivity samples proportion of anti-HCV detection was 0.19 ％ (252/133959),27 cases were positive in NAT detection with the positive detection ratio of 0.02 ％ (27/113 380);the proportion of HCV reactive samples confirmed by RIBA was 19.8 ％ (50/252),the negative proportion was 54.8％ (138/252),and the uncertain proportion was 25.4％ (64/252);27 samples of nucleic acid detection positive were double reagent reactivity in ELISA detection and positive in confirmatory test.The difference among the results of two ELISA reagents,RIBA confirmatory test results and nucleic acid detection results had statistical significance(P＜0.05).Conclusion The detection strategy selecting twice ELISA+1 kind of nucleic acid detection is more secure.Aiming at higher proportion of false positive samples,the follow up system of blood donors should be established for maximizing the retention of blood donors.