Objective To establish a highly sensitive,stable,and universally applicable ultra-high-performance liquid mass spectrometry tandem method(UPLC-MS/MS)for simultaneous determination of nirmatrelvir and ritonavir blood concentrations in human plasma.Methods The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm× 50 mm,1.7 μm)with gradient elution,and the mobile phase consisted of 0.1％formic acid-water and 100％acetonitrile at the flow rate of 0.3 mL·min-1.The column temperature was 45℃,and the injection volume was 2 μL.Electrospray ionization as ion source(ESI+)was used as the ion source and multiple reactions monitoring mode(nirmatrelvir m/z 500.20→319.10,nirmatrelvir-D9 m/z 508.59→328.10,ritonavir m/z 721.30→426.10,13C,2H3-ritonavir m/z 725.30→426.10)was adopted.Thirty patients with coronavirus disease 2019(COVID-19)treated with nirmatrelvir and ritonavir at the People's Hospital of Changxing County in Jan.2023 were selected to measure their steady-state trough concentrations of nirmatrelvir and ritonavir after 3 days of treatment.Results The linear range of nirmatrelvir was 0.100-10.0 μg·mL-1(R2=0.997 2),and the linear range of nirmatrelvir was 0.050-5.00 μg·mL-1(R2=0.995 2).The recovery rates of nirmatrelvir and lopinavir were both＞90％and the intra-batch and inter-batch precision relative standard deviations(RSDs)were both＜10％.Additionally,the recovery ranges for nirmatrelvir and lopinavir were 91.5％-97.0％,and the matrix effects ranged from 92.4％to 97.7％.The results of clinical samples showed that the plasma concentrations of nirmatrelvir and ritonavir in patients with COVID-19 varied greatly among individuals.Conclusion The method for simultaneous determination of nirmatrelvir and ritonavir concentrations in human plasma established in this study is convenient,highly specific,highly accurate,with high precision,which is suitable for monitoring the concentrations of nirmatrelvir and ritonavir in patients.

OBJECTIVE To test and compare the median effective dose(ED50) of ciprofol for gastroscope in patients of different genders and ages. METHODS Patients who planed to undergo gastroscope examination and treatment from March 2023 to April 2023 were selected, and divided into four groups according to stratified random method: N1 group(non-elderly male patients), N2 group(non-elderly female patients), N3 group(elderly male patients), and N4 group(elderly female patients). All patients received intravenous injection of 0.1 μg·kg−1 sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Gastroscope was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups was 0.4 mg·kg−1, and the ratio of adjacent doses was 1∶1.1. The next patient would receive a 10% increase in the dose of ciprofol if the patient experienced positive reactions such as coughing, frowning, and body movements during the endoscopy process. Otherwise, it would be judged as a negative reaction, and the next patient would receive a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points. The Probit regression analysis method was used to calculate the ED50 of ciprofol for four groups. RESULTS The ED50 of ciprofol combined with 0.1 μg·kg−1 sufentanil for gastroscope in the non-elderly men, non-elderly women, elderly men, and elderly women were 0.409, 0.373, 0.356, 0.327 mg·kg−1, respectively. The ED50 of ciprofol in the N1 group was significantly higher compared with the N2 group and N3 group(P<0.05). The ED50 of ciprofol in the N4 group was significantly lower compared with the N2 group and N3 group(P<0.05). CONCLUSION The ED50 of ciprofol is significantly different among gastroscope patients of different genders and ages, which is lower in female patients than in male patients, and is lower in older patients than in non-elderly patients.

Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.

Objective To explore the key active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of rheumatoid arthritis(RA)based on the systematic pharmacology and LC-MS/MS technology.Methods The information of active ingredient from Wenxing Jingjintong Gel Patch was established through LC-MS/MS analysis and literature retrieval.The targets of the active ingredients were predicted using Swiss Target Prediction platform and then mapped with the RA-related targets obtained from GeneCards,DrugBank,and OMIM databases to identify the intersecting targets.The"active ingredients-effective targets"network was constructed through the Cytoscape software.The shared targets were imported into STRING database to construct a protein-protein interaction network.GO function and KEGG pathway enrichment analysis were performed using the Metascape database.Molecular docking studies were conducted using AutoDock software to investigate the interactions between key ingredients and target proteins.Results A total of 142 active ingredients were identified in Wenxing Jingjintong Gel Patch by wsing LC-MS/MS,which were further supplemented to 174 through literature retrieval.There were 175 shared targets between the active ingredients and RA.It was anticipated that Wenxing Jingjintong Gel Patch exerted immune regulation and anti-inflammatory and analgesic effects through the interaction between key active ingredients such as berberine,neobavaisoflavone,and palmatine chloride with key targets,including TNF,IL6,and AKT1 to regulate PI3K/Akt1,JAK/STAT,and MAPK signaling pathways.In 1 152 molecular docking validation,94%of them had binding energies less than-5.0 kcal·mol-1,while 51%of them had binding energies less than-7.0 kcal·mol-1.It was indicated that there was a good binding affinity between the potential active ingredients and core targets.Conclusion This study predicted the active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of RA,which provided a theoretical basis for further clinical application and quality control.

【Objective】 To study the relationship between the key influencing factors and the short, medium and long term blood demand, so as to provide basis for building a blood demand prediction model with less prediction error and practical guidance. 【Methods】 Through literature research, the influencing factors of blood demand were preliminarily determined. Questionnaires were designed and distributed to relevant experts, and factor analysis was carried out on the survey results to obtain key influencing factors through Delphi method. 【Results】 Through literature research, 19 influencing factors of clinical blood demand were obtained, including policy factors, medical service demand, medical technology level, regional population, population characteristics, population structure, medical resource, number of beds, culture, natural environment, operation, patients outside the region, blood use in different departments, blood infusion, time trend, emergencies and disasters, the condition of disasters, hospitals in disaster area, limited diagnosis and treatment ability. Through Delphi method and data analysis, six key factors affecting blood demand were obtained, namely sudden disaster, medical resource, environmental factor, population, bed number and blood infusion. 【Conclusion】 The influence of key factors on clinical blood demand was divided into multiple hierarchies. Blood infusion and sudden disaster were short-term influencing factors. Medical resource, population and number of beds were medium influencing factors. Environmental factor was long-term influencing factor. Short, medium and long-term influencing factors were interrelated, and have different impacts on clinical blood demand. Based on the interaction relationship, a three-dimensional mathematical model of influencing factors of clinical blood demand was established, which provided a preliminary research basis for building a blood demand prediction model with less prediction error and practical guidance.

OBJECTIVE To explore the way to re-use epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI） in patients with EGFR-TKI-induced interstitial pneumonia （IP）， using osimertinib as an example. METHODS The IP treatment regimen and re-use of EGFR-TKI regimen in a patient who developed IP after the use of osimertinib were analyzed. And a literature review was made by combining the characteristics of the cases which reported in the literature and the characteristics of this case. RESULTS The patient’s IP symptoms due to treatment with osimertinib had resolved after treatment. The patient’s IP symptoms also did not worsen after using almonertinib in combination with hormones as re-use of EGFR-TKI regimen. However， almonertinib was discontinued as the patient experienced disease progression. The adverse reactions of IP needed to be dealt with in time， the EGFR-TKI should be discontinued and symptomatic treatment should be given. CONCLUSIONS EGFR-TKI targeted therapy could be re-selected by replacing EGFR-TKI， adjusting the dose of EGFR-TKI， and using hormones in combination. EGFR-TKI-induced adverse drug reactions of IP are rare， but need to be observed closely. If other EGFR-TKI is used， close monitoring of adverse reactions and curative effects are also required in order to adjust the patient’s treatment plan in time.

Objective:To explore the clinical application value of 3D printing technology in percutaneous nephrolithotomy(PCNL) to complex renal calculi.Methods:The clinical data of 41 patients with complex renal calculi from May 2018 to October 2019, in the First Affiliated Hospital of Xiamen University and Xiang'an District of the First Affiliated Hospital of Xiamen University were retrospectively analyzed. There were 19 cases underwent PCNL after 3D printing (3D printing group), and 22 cases during the same period did not undergo 3D printing before operation (control group). Before operation, the two groups underwent CT plain scan enhanced examination. In 3D printing group, 3D printing technology was used to obtain 3D renal models, then 3D renal models were used for preoperative design and simulation of surgical puncture and preoperative conversation.The control group only underwent PCNL after routine examination.The ages of the patients in 3D printing group and control group were (42.9±2.5) vs. (41.3±2.9) years old, male/female ratio 11/8 vs. 12/10, body mass index (22.4±1.1) vs. (23.2±1.4) kg/m 2, serum creatinine (42.9±2.5) vs. (78.2±4.5) μmol/L, stone size (5.0±1.2) vs. (5.2±1.3) cm, the CT values of the stones was (930±210) vs.(950±200) HU. The difference of above parameters was not statistically significant ( P>0.05). The following indexes were compared between the two groups: score of questionnaire on satisfaction of preoperative conversation, and datas about operation and postopetation. Results:All the operations were successfully completed. The time of locating the target calyces in 3D printing group and control group was (3.3±1.3) vs. (5.3±3.1) min, and the coincidence of puncture calices was 94.7% (18/19) vs. 54.5%(12/22), and the stone removal rate of the 3D printing group was 78.9% (17/19) vs. 36.4% (8/22), 3D printing group was better than the control group in these respects( P < 0.05). However, there were no significant differences in postoperative complications [21.0% (4/19) vs. 13.6% (3/22)], multi-channel[89.4% (17/19) vs. 86.4% (19/22)], operation time [(121.8±20.2) vs. (132.1±18.5) min], time of hospitalization [(7.6±1.3) vs. (8.0±1.8)d] and time of extubation for renal fistula [(3.8±1.7)vs. (4.5±2.0 )d] (all P > 0.05). During preoperative conversation between the 3D printing group and the control group , the time spent on signing the consent [(17.0±3.9) vs.(21.0±3.3) min], the degree of understanding of the stone condition [(2.5±0.6)vs.(2.0±1.2) points], the degree of understanding of the PCNL surgical process and complications [(2.6±0.6) vs.(1.8±1.3) points] and the degree of satisfaction with the doctor’s preoperative conversation effects [(2.4±0.9) vs.(1.7±1.6) points]were significantly different in comparisons ( P<0.05). Conclusions:3D printing technology can be used in PCNL to directly display the internal anatomical relationship of renal calculi, guide accurate preoperative designing, help improve the operation efficiency and stone clearance rate, and can also be used as a mold in preoperative conversation to improve communication efficiency.

OBJECTIVE:To investigate the effects of dexmedetomidine pretreatment on hepatic ischemia-reperfusion injury in patients with hepatocellular carcinoma radical surgery (HCRS).METHODS:A total of 40 patients underwent elective HCRS were randomly divided into control group (20 cases) and observation group (20 cases).Before operation,observation group was given Dexmedetomidine hydrochloride injection with loading dose of 0.7 μg/kg within 10 min,maintained at 0.4 μg/(kg.h) until the end of surgery.Control group was given constant volume of 0.9％ Sodium chloride injection as observation group and same anesthetic scheme.The levels ofALT,AST,IL-1,IL-6,CRP and TNF-α,the occurrence of ADR were observed in 2 groups before surgery,4 h,24 h,72 h after surgery.RESULTS:Before surgery,there was no statistical significance in the levels ofAST,ALT,IL-1,IL-6,CRP and TNF-α between 2 groups at different time points (P＞0.05).After surgery,the levels of AST and ALT in 2 groups were significantly higher than before surgery,and the observation group was significantly lower than the control group,with statisti-cal significance (P＜0.05).The levels of AST and ALT in 2 groups were decreasing gradually as time.4,24,72 h after surgery,the levels of IL-1 and IL-6 in 2 groups,TNF-α levels 4,24 h after surgery and CRP levels 24,72 h after surgery were significantly higher than before surgery,and the observation group was significantly lower than the control group;the levels of TNF-α in 2 groups 72 h after surgery were significantly lower than before surgery,with statistical significance (P＜0.05).The levels of IL-1,IL-6 and TNF-α were decreasing gradually as time.There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Dexmedeptomidine pretreatment can relieve hepatic ischemia-reperfusion injury in HCRS patients,reduce the level of inflammatory cells without increasing the occurrence of ADR.

Objective To evaluate the effect of awake tracheal intubation with intubating larynegeal mask airway (ILMA) on stress responses of hypertensive patients.Methods Sixty hypertensive patients,aged 45-64 yr,with body mass index of 20.3-27.5 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective abdominal surgery under general anesthesia,were divided into 2 groups (n=30 each) using a random number table:direct laryngoscope group (group D) and ILMA group (group I).At 3 min after topical anesthesia (T1),while epiglottis and glottis were exposed with direct laryngoscope in group D or during ILMA insertion in group I (T2),immediately after completion of intubation (T3),when the maximum change in hemodynamics after intubation appeared (at about 15 s after tracheal tubes were placed,T4),and at 5 min after completion of intubation (T5),mean arterial pressure (MAP) and heart rate (HR) were recorded,and blood samples were collected for determination of plasma epinephrine concentrations by radio-immunity method.Successful intubation at first attempt was recorded.Results Compared with the parameters at T1,the MAP,HR and plasma epinephrine concentrations were significantly increased at T2-4 in group D (P＜0.01),and no significant change was found in the parameters mentioned above at the other time point in group I (P＞0.05).Compared with group D,the MAP,HR and plasma epinephrine concentrations were significantly decreased at T2-4 (P＜0.01),and no significant change was found in the success rate of intubation at first attempt in group I (P＞0.05).Conclusion Awake tracheal intubation with ILMA does not induce strong stress responses and is helpful in avoiding the occurrence of cerebrovascular accidents,thus increasing the safty of awake tracheal intubation in hypertensive patients.

Objective To observe the rotation of subendocardium and subepidium by two-dimensional speckle tracking imaging(2D-STI),and to evaluate its performance in diastolic heart failure patients(DHF)with a normal left ventricular ejection fraction. MethodsNinety-seven consecutive clinically stable patients were enrolled in this study [41 healthy controls,36 with diastolic heart failure,20 with systolic heart failure (SHF)]. High frame rate dynamic two-dimensional images were recorded at the left ventricular short-axis view,including basal, papillary muscle and apical planes. Subendocardial and subepicardial global rotation were measured using Q-lab 7.0 software offline. Results ① In all the subjects, the rotation of the subendocardium was obviously greater than that of subepicardium. ②As seen from the apex,left ventricular subendocardium and subepicardium performed a wringing motion with a clockwise rotation at the base and countclockwise rotation at the apex. ③In the apical plane, subendocardial rotation was significantly lower in both heart failure groups than in controls,and was depressed to a larger extent in SHF patients than in those with DHF. Subepicardial rotation was no significant difference between the DHF group and the control group, though it was significantly lower in patients with SHF. ④At the base, the rotation of subendocardium and subepicardium were not different between DHF and control groups, but it was significantly reduced in patients with SHF. Conclusions The subendocardial rotation is reduced, but subepicardial rotation is normal in DHF patients. On the other hand, in patients with SHF, subendocardial and subepicardial rotation are both reduced. The left ventricular systolic properties are impaired in DHF patients.